CA2392642A1

CA2392642A1 - Methods and apparatus for delivering medicament to tissue

Info

Publication number: CA2392642A1
Application number: CA002392642A
Authority: CA
Inventors: Don Bobo Jr.
Original assignee: Individual
Current assignee: Edwards Lifesciences Corp
Priority date: 1999-12-02
Filing date: 1999-12-02
Publication date: 2001-06-07
Also published as: JP2003515383A; EP1235526A1; AU782484B2; AU3108100A; WO2001039682A1

Abstract

A system for delivering medicaments to tissue includes a tissue-removal and medicament-delivery device. The device includes a delivery member and an optical fiber formed together into a unitary structure by cladding. The optical fiber has an inlet for receiving laser energy from a laser energy source and an outlet for emitting laser energy. The delivery member has an inlet for receiving medicament from a medicament source and an outlet for injecting medicament. A handpiece is adapted to receive the ablating and injecting device in a controlled and movable relationship. In use, a distal end of the handpiece is placed against tissue to be ablated. The ablating and injecting device is advanced beyond the distal end of the handpiece and into the tissue while emitting laser energy from the optical fiber. The emitted laser energy ablates the tissue as the optical fiber advances. The ablating and injecting device is then retracted from the tissue, thereby resulting in a channel formed in the tissue. While the device retracts, medicament is injected from the delivery member into the channel, thereby providing a plug within the channel. Alternatively, medicament may be injected into the tissue surrounding the channel by delivering the medicament into the tissue surrounding the channel opening or delivering it directly into the channel wall. The medicament may include growth factor combined with a cellular matrix which enhances angiogenesis in the tissue or may include a gene that encodes for said growth factor, or any other therapeutic agent or gene therapy agent that promotes angiogenesis or any therapeutic agent for the treatment of cardiovascular disease. The medicament delivery system is particularly useful in cardiac applications for performing transmyocardial revascularization (TMR) in ischemic myocardium and promoting endothelial cell growth within the myocardium.

Description

METEIODS AND APPARATUS rOR DELIVERING MEDICAMENT TO TISSUE
MELD OF Ti-lE INVENTION
The present invention is directed t0 surgical methods and apparatus for delivering medicament to tissue. l~~lore particular(~~, the present invention is directed to surgical methods and apparatus for delivering medicament to tissue by first removing tissue to form a hole or channel in the tissue and then delivering medicament into the hole or channel or into the tissue surrounding the hole or channel. The methods and apparatus of the present invention may be applied in delivering growth factor to cardiac tissue dlll'lll~
transmyocardial revascularization.
BACKGROUND O1~ TIIE INVENTION
Cardiomyopathy ~C'Cll'c~lU Illealllllg "heart" and mt~ohcrlly meaning "muscle disease") refers to a group of disorders that directly damage the muscle of tire hearrt walls, or nryocamlimu. In these disorders, all chambers of the heart are affected. The heart's function as a pump is disnrpted, leading to an inadequate blood flow to Organs alld tissues of the body.
Depending on the nature of the injury or abnormality in the heart muscle and the resulting structural changes in the heart chambers, one of three types of nonischemic (that is, not caused by heart attach) heart muscle disease may be present in a patient: clilcrt~cl cmylu.wine, hypertj~op~~ic, or re.sw~icto~.
Dilated congestive cardiomyopathy damages the fibers of the heart muscle, weakening the wails of the heart's chambers. The chambers thereby lose some of their capacity to contract forcefirlly and pump blood through the circulatory system. To COIIl1J2r1Sate for the muscle injury, the heart chambers enlarge or dilate which causes heart failure.
Hypertrophic cardiomyopathy is characterized by a disorderly growth of heart muscle fibers causing the heart chambers to become thick walled and bulky. The thickening is generally most strikin g in tire walls of the left ventricle, the clamber of the heart which pumps blood through the aorta to the vital organs and tissues of the body. The distorted left ventricle contracts, but the supply of blood to the brain and other vital organs may be inadequate because blood is trapped within the heart during contractions. Restrictive cardiomyopathy causes abnormal cells, proteins, or scar tissue to infiltrate the muscle and structures of the heart, CalISlilg the C11a111berS to become stiff and bulky. The heart may initially contract normally, but the rigid chambers restrict the return of blood to the heart.
Massive or multiple heart attacks may also lead to severe heart damage as a result of a disruption of blood supply to heart muscle. The damage can result in functional impairment and structural abnormalities similar to those found in the other types of cardiomyopathy. This type of heart disease, resulting from coronary artery disease, is called l.S'c~)~nllc ccrrcfinnryupcrllm~
(i.sclrerrric meaning "lacking o~:ygen").
Severe heart injury caused by a major heart attacks or multiple smaller heart attacks may result in heart enlargement and thinning of the chamber walls, abnormalities which resemble those observed in dilated cardiomyopathy. 1SC11e1111C ClrdlonlyOpathy typically develops in patients with severe coronary artery disease, often complicated by other conditions such as diabetes and hypertension.
Although heart failure symptoms in ischemic cardiom~~opathy are similar to those found in dilated cardiomyopathy, ischemic disease is more likely to be accompanied by Sv111ptOmS Of coronary artery disease, such as angina (which is chest pain resulting from reduced oxygen supply to the heart muscle). Diagnosis is typically based on a history of heart attacks and studies that demonstrate poor fU11Ct1011 111 llla~Or portions of the left ventricle. The diagnosis can be confirmed by coronary angiography, which reveals areas of narrowing and blockage in the coronary blood vessels.
Patients with ischemic cardiomyopathy are treated with medications that relieve heart failure symptoms and improve blood flow throu~,l~ the diseased coronary arteries, such as nitroglycerin, some types of calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. When symptoms of heart failure and coronary artery disease cannot be controlled with medications, coronary angioplasty or surgery may be considered. Angioplasty ?5 and coronary artery bypass grafting may help increase blood flow to the heart, which in turn enhances heart muscle function.
When heart failure symptoms are advanced and Cannot be improved by drug theraly~ or surgery, patients may be referred for a heart transplant. Patients with isciemic cardiomyopatlly account for approximately one half of all heart transplant recipients. With a limited supply of donor hearts and complications resulting from heart transplant (such as organ rejection), surgeons have been exploring alternative procedures for treating severe ischemic cardiomyopathy. One such procedure is ~rcrn.wy~uwrmlinl r~mn.~~cnluri_cr~iun, otherwise known more simply as "TMR."
TMR procedures revascularize, that is, form new channels, in the heart muscle or myocardium. The newly formed channels penetrate through the entire heart wall, which S includes the epicardirrrn (the outer layer of the heart), the errcluccrrclimn (the inner lining of the heart), and the myocardium or muscular wall therebetween. As ischemic cardiomyopathy more often than not afflicts the left ventricle, the new channels are typically formed in tire hearrt wall oi~
this chamber of the heart. Accordingly, oxygenated blood from the lungs present in the left ventricle awaiting to be pumped through the aorta is able to flow directly into the newly formed channels to nourish the heart muscle.
Pioneering methods for performing TMR involved the use of needles for physically puncturing holes in the heart wall. These methods resulted in only a temporary delivery of blood to the myocardium because the holes quichfy heated at the endocardiun~, preventing oxygenated blood from entering the myocardium. One of the more recent and exciting methods 1S of performing TMR is through the use of lasers. It has been observed that new holes or channels formed in the heart wall by a laser tend to heal at the epicardium, which prevents blood loss, and promote blood perfusion into the ischemic region of the myocardium.
Lasers have proven to be a widely useful and applicable tool in modern medical techniques, particularly in minimally invasive surgical procedures.
Technically speaking, a laser (the word laser being an acronym for light amplification by .stimulated c.~mission of radiation) utilizes the natural oscillations of atoms or molecules between energy levels for generating coherent electromagnetic radiation. A laser is able to produce high-intensity and hi~,lr-energy light at a single frequency. The energy of laser light is measured in joules (J), or watt-seconds (W-s), and the power of a laser is measured in watts (W).
2S One of the conventional surgical apparatus for performing TMR consists of a laser anti an optical fiber. A surgeon places the end of the optical fiber against the epicardium to ensure that all the laser light is focused at the desired point, and then the laser is fired. In order to form the new channel completely through the heart v.vall and into the chamber, the sur~~eon needs to tactilely urge the optical fiber into and tiu-ou~~h the epicardium, the myocardium, and tl~e endocardium. Because of the nature of ischemic cardiomyopathy, the thickness of the diseased myocardium is irregular and greater than normal. Accordingly, the surgeon needs to tactilely urge the optical fiber through the heart wall at each location. This procedure takes a certain - J -amount of time to accomplish safely and involves a certain amount of guessworl: on the part of the surgeon. This procedure is complicated by the beating of the heart.
Accordingly, the firing of the laser needs to be synchronized with the beating of the heart. In addition, irregularly shaped holes may result if the surgeon does not urge the optical fiber into the tissue at a constant rate. For example, a cavity within the new hole may be formed if the surgeon slowed down or paused briefly at a particular location because more tissue at that location would be ablated by the increase in laser energy emitted over time. In addition, the increase in emitted laser energy may cause excessive trauma to the surrounding tissue at that location.
In many surgical applications, it may be desired to drill as large a hole as possible. For example, in treating ischemic myocardium, holes with larger diameters have larger inner surface areas; accordingly, more blood is able to perfilse into the ischemic tissue.
The diffiiculty in drilling relatively large holes (for example, about I 111111) with laser ablation is that the area of the lasing plenum increases exponentially with an increase in the diameter of the hole (the la.s~iyT
plenrmr being defined as the "bottom" of the hole subject to emitted laser energy). For example, the ratio between the areas of the lasing plenum of a hole with a 0.~-mm diameter and a hole with a 1-mm diameter is four. Conventional practice has been to increase the diameter of the optical fiber and, accordingly, the diameter of the laser beam to form larger holes. The power of the laser may also be increased. However, increasing the diameter of the laser beam results in an increase in the amount of energy emitted and, accordingly, an increase in the trauma of the surrounding tissue. In addition, the power of the laser energy call only be increased to a certain point until the capacity of the optical fiber is exceeded.
Accordingly, in view of the foregoing, it is an object of~the present invention to provide methods and associated apparatus for delivering medicaments to tissue in a consistent and controlled manner.
It is another object of the present invention to provide surgical apparatus for fornllng either complete or partial 1101eS lil tISSlle alld then dellVerlllg inedlCa111e11tS t0 the 1101eS and/or to surrounding myocardium tissue.
It is a fill-ther object of the invention to provide surgical apparatus and methods for promoting angiogenesis and endothelial growth in tile I11~~OC11'dilllll.
It is yet another object of the present invention to provide methods and associated apparatus for delivering medicaments to the myocardium while performing transmyocardial revascularization.

sun~nnaa~~ or T~I:E >INVrNTioN
These and other objects are achieved by the surgical apparatus and associated methods of the present invention which provides a medicament delivery system which forms holes or channels in tissue by removing tissue and then delivers medicament to the hole or channel or to the tissue surrounding the hole or channel. Tissue is preferably removed with laser ablation but may be removed by other methods, for example, with high-frequency electrical energy.
The system for delivering medicament to tissue in accordance with the present invention may be utilized to form a hole or channel in tissue, for example, cardiac tissue (myocarcllum), and then to deliver medicament, for example, a therapeutic went for the treatment of cardiovascular disease, a growth factor that promotes angiogenesis, a gene that encodes for said growth factor, or any other therapeutic agent or gene therapy went that promotes angiogenesis, to the tissue by partially or fully filling the hole or channel with the medicament, or by injecting the tissue surrounding the hole or channel with the medicament. This process may be repeated a plurality of time to form and fill a plurality of holes and CllallIleIS In a targeted area of tissue. In contrast to conventional systemic delivery approaches, the medicament-delivery system of the present invention delivers medicament in a controlled manner to specific targeted tissue.
The medicament-delivery system of the invention may form channels in targeted tissue by removing tissue with laser ablation. It has been found that tissue ablation with laser energ~~ stimulates a natural biological process of an~io~enesis in the bean. In addition, administering IlledICilnlelltS SIICh as growth factors that promote an~io~enesis Dave been fbund to promote angiogenesis irl the heart.
Accordingly, a SyllergIStIC StlllllllatlOn al7d pl-o1170tIOn Of angio~,~enesis in the heart is created by augmenting the hearrt's natural angio~;enic response to laser ablation with the delivery ofgrowth factor to those areas of the myocardium which have been ablated. The coupling of the heart's natural response to the foCmatlon Of CllanIleIS Wlth the delivery of growth factor into or adjacent to those channels provides a benefit to patients not heretofore possible.
In a broad aspect of the present invention, a system for delivering medicaments to tissue includes an ablating and injecting device and a handpiece. ~'he ablating and injecting device includes an optical fiber and a delivery member formed together Into a unltaly structure with cladding. The optical fiber has an inlet for receiving laser energy from a laser energy source and an outlet for emitting laser energy. The delivery member has a lumen with an inlet for receiving medicament from a medicament source and an outlet for injecting medicament.
The handpiece is adapted to receive the ablating and injecting device in a controlled and movable relationship.

In use, a distal end of the handpiece is placed against the target tissue. The ablating and injecting device is advanced beyond the distal end of the handpiece and into the tissue while emitting laser energy from the optical fiber. The emitted laser energy ablates the tissue as the optical fiber advances. The ablating and injecting device is then retracted from the tissue, thereby resulting in a channel formed in the tissue. While the device retracts, medicament is injected from the delivery member into the channel, thereby providing a plug within the channel.
The medicament may include growth factor alone or in combination with a cellular matrix which enhances angiogenesis in the tissue.
Other aspects, features, and advantages of the present invention will become apparent to those persons having ordinary skill in the alrt to which the present invention pertains from the following description takell 111 COn ~LI11Ct1011 \'VI2I7 the accompanying drawings.
I3RiCl~ DCSCR11'TION O~ Tllr DRA~VIIVGS
FIG. 1 is a perspective view of an exemplary embodiment of a tissue drill of the present mventlon;
FIG. I A is a cross-sectional view of an exemplary optical fiber of the invention taken along line 1 A of FIG. 1;
FIG. 2A is a diagrammatic view of the exemplary tissue drill of the present invention, illustrating a handpiece receiving an optical fiber in a retracted position;
FIG. 2B is a diagrammatic view similar to that of F1G. 2A, illustrating the optical fiber in an advanced position;
FIG. 3A is a diagrammatic view of an exemplary handpiece of the tissue drill of the present invention, illustrating the 11a11dpleCe dISaSSelllbled;
FIG. 3B is a diagrammatic view similar to that of F1G. 3A, illustrating the handpiece assembled;
FIG. 4 is a schematic view of an exemplary optical fiber of the present invention, particularly illustrating an eccentric configuration of an outlet portion of the optical fiber;
FIG. 5 is a schematic view of an end surface of the optical fiber illustrated in FIG. 4;
FIG. 6 is a schematic view of another exemplary optical fiber of tile present invention;
F1G. 7 is a schematic view of an end surface of the optical fiber illustrated in F1G. 6;

FIG. 8 is a diagrammatic view of an exemplary end surface of an optical fiber of the present invention, particularly illustrating a relationship between emitted laser enemy and position of the end surface;
FIG. 9 is a schematic view of an exemplary source of laser energy of the present invention;
FIG. 10A is a schematic view of an exemplary tissue drill of the present invention, particularly illustrating a step of a preferred tissue-drilling procedure implementing tl~e tissue drill;
FIG. lOB is a view similar to that of FIG. 10A, illustrating a subsequent step in the tissue-drilling procedure;
FIG. l OC is a view similar to that of FIG. I OB, illustrating another subsequent step in the tissue-drilling procedure;
FIG. lOD is a view similar to that of FIG. l OC, illustrating yet another subsequent step in the tissue-drilling procedure;
FIG. 1 1 is a schematic view of tissue in which a hole has been drilled according to an exemplary method of the invention;
FIG. 12 is a schematic view of tissue in which a hole has been drilled according to another exemplary method of the invention;
FIG. 13 is a perspective view of an exemplary medicament delivery system configured in accordance with the present invention;
FIG. 14 is a schematic cross-sectional view of an exemplary ablating and injecting device for use in the medicament delivery system of the present invention;
FIG. 15 is a schematic view of an end surtoce oftl~e ablating and injecting illustrated in FIG. 14;
FIG. 16 is a schematic view of an exemplary source of laser energy and medicament for use in the medicament delivery system of the present invention;
FIG. 17A is a schematic view of an exemplary medicament delivery system of the present invention, particularly illustrating a step of a preferred medicament-delivery procedure of the invention;
FIG. 17B is a view similar to that of FIG. 17A, illustrating a subsequent step in tl~e medicament-delivery procedure;
_7_ FIG. 18 is a perspective view of a tissue-removal and medicament-delivery system in accordance with the invention, particularly illustrating a coupling assembly of the invention;
FIG. 19 is a cross-sectional view of an exemplary coupling assembly taken along line I9-19 of FIG. 18, with medicament injection and supply units shown schematically;
S FIG. 20 is a diagrammatic view of an alternative embodiment of an exemplary ablating and injecting device for use in the medicament delivery system of the present invention;
FIG. 21 is a diagrammatic view of another embodiment of an exemplary ablating and injecting device for use in the medicament delivery system of the present invention;
FIG. 22 is a cross-sectional view of a tissue-removal and medicament-delivery device of IO the present invention, particularly configured to remove tissue with high-frequency electrical energy;
FIG. 23 is a cross-sectional view of an alternative embodiment of a tissue-removal and medicament-delivery device of the present invention;
FIG. 24 is a schematic view of a step of a tissue-removing procedure incorporating the 1 S device of FIG. 22 or 23, particularly removing tissue with high-frequency electrical energy according to the invention;
FIG. 25 is a schematic view of a medicament-delivery step of the invention, particularly illustrating the delivery of medicament to tissue surrounding a hole or channel formed in tissue;
FIG. 26 is a cross-sectional view of another elllbOdllllellt of an electrical-energy tissue-20 removal and medicament-delivery device in accordance with the invention;
F1G. 27 is a schematic view of another embodiment of a medicament-delivery system of the invention, particularly illustrating an ablating and ilecting device received within a catheter with rifling FIG. 28 is a cross-sectional view of the medicament-delivery system of F1G.
27;
25 FIG. 29 is a developmental view of an exemplary catheter with rifling for else In the medicament-delivery system of FIG. 27;
FIG. 30 is a schematic view of an exemplary medicament delivery system of the present invention, illustrating needles around the perimeter of the head portion of the handpiece;
FIG. 31 is a schematic view of the end surface of the head portion of FIG. 30;
30 FIG. 32 is a schematic view of the embodiment of FIG. 30, particularly illustrating a step of a preferred medicament-delivery procedure of the invention;
_g_ FIG. 33 is a schematic view of another exemplary embodiment of the head portion of the handpiece, illustrating nozzles around the perimeter of the head portion of the handpiece;
FIG. 34 is an end view of yet another exemplary embodiment of the head portion of the handpiece, illustrating ports around the perimeter of the head portion of the handpiece;
FIG. 35 is a perspective view of an alternative embodiment of a tissue-removal and medicament-delivery device of the present invention utilizing a single delivery lumen;
FIG. 36 is a schematic cross-sectional view of the embodiment of FIG. 35;
FIG. 37 is a perspective view of yet another embodiment of a tissue-removal and medicament-delivery device of the present invention utilizing a single delivery lumen;
F1G. 38 is a schematic cross-sectional view of yet another embodiment of of the device of the present invention utilizing at least one vacuum lumen and at least one delivery lumen;
FIG. 39 a schematic cross-sectional view of a step of an alternate exemplary embodiment of an electrical-energy tissue-removal and medicament-delivery device of the present invention; and FIG. 40 is a schematic cross-sectional view of the embodiment of FIG. 39, particularly illustrating a step of a preferred medicament-delivery procedure of the invention.
DE'I'AILCD DESCRII''1'ION O1~ l:Xl.Nll'LAR1' E11~1I30DIMCN'rS
Referring to the drawings in more detail, in FIG. 1 an exemplary embodiment of a tissue drill 50 of the present invention is illustrated in conjunction with a source of laser energy 5~.
Exemplary tissue drill 50 forms holes or channels in tissue by laser ablation in a consistent, controllable, and programmable manner. The first portion of the following description focuses on the principles of tissue ablation and the forming of channels in tissue.
These princilales of the present invention are then readily applied to a system for delivering medicaments to the tissue in which the channels are formed, which will be discussed in more detail below.
Ablation is the process of fragmenting long molecules into short gaseous molecules.
Much of the tissue in living organisms, including the human body, is made up mostly of water (e.g., about 75%) with organic material making up the remaining portion. The molecules of organic material consist of atoms of carbon, nitrogen, oxygen, and hydrogen that are attached together through covalent bonds. Ablation is the process of breaking these covalent bonds.
Tissue drill 50 utilizes the ablation process to breal: molecules of tissue apart, thereby forming holes or channels in the tissue. The ablation process will be discuss in more detail below.

Exemplary tissue drill 50 includes a handpiece 54 for I17a111pUlat1o11 by a user and an optical fiber 56, which is shown in FIG. 1 A, for t1'allSllllttlllg IaSer ellel'gy 8'0111 laser energy source 52. Optical fiber 56 has an outlet portion 58 for emitting laser energy. Outlet 1)oaion 58 functions substantially as a drill bit. In operation, outlet portion 58 is moved from a retracted position (which is shown in the solid line) to an advanced position (which is shown by the phantom line) while emitting laser energy. Arrov.v A represents outlet portion 58 moving to the advanced portion, and arrow L represents laser energy emitted from outlet portion 58. Tissue is ablated by laser energy as outlet portion 58 is advanced, thereby forming a hole or a channel in the tissue. Exemplary tissue drill 50 may also rotate outlet portion 58 while moving to the advanced position, which is represented by arrow R. After- reaching the advanced position, outlet portion 58 may be withdrawn to the retracted position, which is represented by arrow Q.
The advancing and retracting of outlet portion 58 is preferably along a central axis of optical fiber 56. Any rotation of outlet portion 58 is preferably about the central axis of optical fiber 56. The axial and rotational movement of outlet portion 58 will be discussed in more detail below.
Exemplary outlet pol-tion 58 of optical fiber 56 has an end surface 60 with an outlet 62 from which laser energy is emitted. Outlet 62 is preferably offset from or eccentric to the central axis of outlet portion 58 so that as outlet portion 58 rotates, outlet 62 rotates about the central axis. Accordingly, laser energy emitted from outlet 62 as outlet portion 58 rotates is not focused at a single point but is rather distributed about the central axis.
Alternatively speaking, the eccentric relationship of outlet 62 with respect to the central axis of outlet portion 58 preferably produces a gradient of laser energy as outlet portion 58 axially advances, with the highest level of laser energy at the central axis, wflich energy decreases toward a peripheral edge. The eccentricity of outlet portion 58 will also be discussed in more detail below.
I-landpiece 54 may be implemented accorclin~ to a variety of COIIfI~lIratI011S. For example, handpiece 54 may be a flexible catheter utilized in endovascular procedures and IlaVlll~
a plurality of lumens to facilitate visualization, tlusl~ing, and aspiration.
In this regard, outlet portion 58 may advance beyond a distal end of the catheter to vascularize tissue, such as on the inside the left ventricle of the heart. Alternatively, handpiece 54 may be formed as a trocar sheath and positioned intercostally (i.e., between the ribs) for tissue access. I-landpiece 54 may, also be formed in a gooseneck-like configuration with a plurality of al'tlClllated JOIIItS W111C11 Illa~' be bent to assume and retalil a pa1-tlClllar Shape. ~'fOreOVel~, ha11dp12Ce 5~1 lllay be a COIICIIiIt \'Vlth flexible cable sheathing. Accordingly, in a general sense, handpiece S4 provides a "user interface" for delivering outlet portion S8 to a target site, which may be accomplished either by direct physical manipulation by a surgeon or by programmed mechanical control.
An exemplary handpiece of the present invention is illustrated in FIGS. 2A and 2B.
Exemplary handpiece S4 may include a hotly portion 64 and a coupling portion 66. Exemplary body portion 64 has a distal end 68. Exemplary coupling portion 66 is adapted or configured to receive optical fiber S6 in a controlled and axially movable relationship so that outlet portion 58 may be advanced beyond distal end 68 of body portion 64. In addition, coupling portion 66 may be adapted to receive optical fiber S6 in a rotatable relationship so that at least outlet portion 58 of optical fiber 56 may rotate. If handpiece 54 is configured as a catheter or similar flexible tubular member, the inner surface of tl~e tubular member serves as a coupling portion by receiving optical fiber S6 in a controlled, axially movable, and/or rotatable relationship.
The retracted position of outlet portion S8 itS SIIO~VII I11 FIG. 2.A may be defined as a position in which end surface 60 is positioned substantially at or near distal end 68 of body portion 64. Accordingly, end surface 60 may project slightly beyond distal end 68 or, alternatively, may be either proximal to or substantially aligned (or coplanar) with distal end 68.
The advanced position of outlet portion S8 as shown in F1G. 2B may be defined as a position in which end surface 60 with outlet 62 projects a distance cf beyond distal end 68 of body portion 64. As will be discussed in more detail below, distance cl at which end surface 60 projects beyond distal end 68 is preferably predetermined, adjustable, and/or prOgrillllillable.
With additional reference to FIGS. _~A and 3B, exemplary coupling portion 66 may include a drive which is comprised of a tubular member 70 and a collar 72.
Tubular member 72 receives optical fiber S6 and may have a chuck 74 for retaining optical fiber S6 thereto. Tubular member 72 may also have annular threading 76 formed along a length thereof.
Collar 72 is disposed within body portion 64 and has Complementary inner threading 78.
Exemplary tubular member 72 is slidably and rotatably receivable within body portion 64 with annular- threading 76 engaging with inner threading 78 of collar 72, aS Showll Ill FIG. 3B.
Accordingly, rotation of tubular member 70 causes tubular member 70 to move axially. As optical fiber 56 is retained by chuck 74, optical fiber 56 with outlet portion S8 moves axially with tubular member 70. In an alternative embodiment of handpiece 54 such as a catheter, rather thall disposing couplinyl portion 66 and a drive on iandpiece S4, these elements may be provided at a proximal lOCatioll, such as at laser apparatus S2. In this regard, catheter-configured handpiece S4 retains optical fiber 56 within a body portion which prevents buckling and which delivers outlet portion 58 to a target site but which is substantially free of coupling and drive apparatus.
Referencing FIG. 4, in addition to outlet portion 58, exemplary optical fiber 56 has all elongate portion 80. A core 82 and a cladding 84 define optical fiber 56 and extend along elongate portion 80 and outlet portion 58. Core 82 has an inlet 86 for receiving laser energy and outlet 62 (see also FIG. 1 ) for emitting laser energy. Core 82 arid cladding 84 may be made of high-purity silica glass or sapphire, with core 82 having a higher index of refraction than that of cladding 84 so that modulated pulses of laser energy move along core 82 without penetrating cladding 84. Although optical fiber 56 may be configured according to any dimensions, for many applications a length l~ of elongate portion 80 may range from about 0.5 meter (m) to more than 2 m to provide a surgeon with sufficient maneuverability, and a length I" of outlet portion 58 may range up to about 50 millimeters (mm) so that holes of different lengths may be formed in tissue. For applications other than medical, optical fiber 56 may be dimensioned accordingly to accomplish the particular application.
1 S Core 82 of optical fiber 56 has an axis E along elongate portion 80 and an aXls O at outlet 62. With additional reference to FIG. 5, core 82 along outlet portion 58 angles away from and is oblique to core 82 along elongate portion 80. At end surface 60, axis O of core 82 at outlet 62 is offset from or eccentric to axis E of core 82 of elongate portion 80 by a distance 8. Accordingly, laser energy emitted from outlet 62 is distributed about axis E as optical fiber 56 rotates about axis of rotation E. Further, the distribution of laser energy is across the entire surface area of end surface 60 as optical fiber 56 make one complete revolution. At end surface 60, outlet 62 may be configured so that axis O of core 82 is either oblique to axis E or, as shown, parallel to axis E.
An alternative exempalary embodiment of optical fiber 56 is illustrated in FIGS. 6 and 7.
In addition to core 82 and cladding 84, exemplary optical fiber 56 may include auxiliary cladding 88 disposed about outlet portion 58. Similar to tire embodiment shown in FIG.
4, to offset axis O of outlet 62 from axis of rotation E by distance 8, core 82 of outlet portion 58 is oblique to core 82 of elongate portion 80. Auxiliary cladding 88 compensates for the oblique relationship of core 82 (and cladding 84) of outlet portion 58 with respect to core 82 (and cladding 84) of elongate portion 80. Auxiliary cladding 88 accordingly provides a preferred cylinc(rical configuration of outlet portion 58 so that outlet portion 58 rotates about axis E as elongate portion 80 rotates about axis E. Further, in addition to axis O at outlet 6~
being eccentric t~

axis E, axis O of core S2 may be oblique to axis E at outlet 62, rather than a parallel relationship as shown in FIG. 4.
As illustrated in FIGS. 6 and 7, end surface 60 (including outlet 62) is substantially perpendicular to axis E of exemplary optical fiber 56. To form the perpendicular relationship, core 82 and cladding 84 are ground or polished at an angle oblique to axis O, thereby removing portions of core 82 and cladding 84 shown by phantom line f. Accordingly, exemplary end surface 60 is substantially planar. Alternatively, end surface 60 may be convex, concave, or other configuration depending upon a particular implementation of outlet portion 58.
With particular reference to FIG. 7, end surface 60 of exemplary optical fiber 56 has a circumference CCS defined along an outer edge 90, and outlet 62 of core 82 has a circumference Co defined along outer edge 92. Circumference C~, and circumference C" are coextensive along an arc length a of outer edges 90 and 92. This relationship allows laser energy to be emitted from outlet 62 at outer edge 90 of end surtnce 60. As outlet portion 58 rotates, laser energy is emitted along circumference C~, of rotating end surface 60. Arc length a may rage ti-om a single tangent point to several seconds, minutes, or degrees as desired.
Diameter d~ of outlet 62 is preferably greater than about one half of diameter d~, of end surface 60. Accordingly, outlet 62 has a surface area which is at least one quarter of that of encf surface 60. This relationship in surface area allows laser energy to be emitted from a substantial percentage of end surface 60. Further, laser energy is not emitted from the entire end surface 60 simultaneously but rather over the time it takes outlet portion 58 to make one revolution about axis E. An exemplary commercial embodiment of optical tiber ~6 for use in transmyocardial revascularization entails a diameter d~, of end surface 60 (and outlet portion 58 of approximately 1 mm and a diameter d~ of outlet 62 of approximately 0.6 mm. Generally speaking, the dimensions of outlet portion 58 are determined by the type of procedure being performed and the desired size of the hole, with diameter d" of~outlet 62 being at least one half of diameter d"
of end surface 60. For example, if a hole with a 1.5-mm diameter is desired, then diameter d~, of end surface 60 (and outlet portion 58) should be about 1.~ mm; diameter d" of outlet 62 may accordingly range from about 0.75 nun to slightly less than I .J mm, but is preferably about O.S
mm. For many medical applications, it is contemplated that diameter d~, of end surface 60 may range from about 0.2 mm to more thal7 2.5 mm, with diameter d" of outlet 62 ranging from less than about 0.1 mm to about 2 mm or more. For specific medical applications such as transmyocardial revascularization (which will be discussed below), diameter d~, of end surface - I _s -60 may range from about 0.6 111111 to about 2 111111, \vlth Cllameter d" of outlet 62 ranging from about 0.3 mm to about I 111111.
With additional reference to FIG. 8, end surface 60 is schematically illustrated during rotation, with outlet 62 shown at progressive instances in time t,, t~, I3, and t4 while rotating about axis E. Because of the relationship between the surface areas of end surface 60 and outlet 62, laser energy is continuously emitted from an area 94 of end surface 60. In other words, area 94 represents an intersection of the positions of outlet 62 at every instance of time while rotating about axis E. Laser energy is accordingly emitted at intervals at other areas of end surface 60 depending upon the position of outlet 62 at a particular instance in time.
The relationship between laser energy emitted from exemplary end surface 60 per revolution of outlet 62 about axis E with respect to distance from axis E is illustrated graphically in FIG. 8. Emitted laser energy her revolution of outlet portion 58 decreases from a constant level at area 94 to a lower level at outer edge 90 of end surface 60. In the graph, outer edge 90 is a distance from axis E substantially equal to radius r~, of end surface 60.
Depending upon a particular configuration of exemplary end surface 60 and outlet 62, the decrease in laser energy or flux with respect to position may be a linear f1111Ct1011 aS ShOwil Or' a nonlinear function. Also, the relative level of energy per revolution at area 94 and at radius r~, is illustrative only, as the level of energy at the periphery of end surface 60 may valy according to the particular surgical procedure. For example, the energy flux at radius r~, may be at a relatively low level when compared to the constant level at area 94.
In accordance with this energy distribution her revolution of the present invention, while ablating tissue to form a hole, the transference of laser energy to peripheral or surrounding tissue is less than at a center of the hole being formed. This distribution of laser energy may limit trauma to tissue in which holes or channels are formed. l~lore specifically, as outlet portion 58 moves through tissue while rotating and emitting laser energy, outer edge 90 of end surface 60 is adjacent to and contacts the surrounding tissue which defines the hole being formed. As the level of emitted laser energy at outer edge 90 is lower than that centered about axis E
(which essentially defines the center of the hole being formed), damage to the surrounding tissue is reduced, resulting in less trauma to the tissue. It is believed that tissue with a relatively low level of trauma has a likelihood to experience angiogenesis, or the formation of new blood vessels in the tissue. This reduced-trauma feature of the present invention will be discussed in more detail below.
I4_ An exemplary process to form an eccentric outlet portion S8 as described above involves placing the distal end of optical fiber S6 within a Teflon'' tube at an angle, with cladding 84 contacting the inner surface of the tube at one point. The tube may then be filled with epoxy which surrounds the distal end of optical fiber S6 except at the point at which cladding 84 S contacts the tube. After the epoxy has cured and hardened, the tube is removed, and the distal surface of the epoxy and optical fiber S6 is polished to define end surface 60 at the point where cladding 84 defines an annular edge of outlet portion S8. End surface 60 may also be formed with a lens to control the emission of the laser enemy in a particular manner.
An inner diameter of the tube for forming outlet portion S8 essentially determines the diameter of outlet portion S8 (i.e., diameter d~s of end surface 60). According to this process, optical fibers S6 having outlet portions S8 of different diameters may be formed, enabling surgeons to form holes with a variety of diameters. In addltloll, a plurality of outlet portions S8 each having a different diameter may be formed, each of which being able to be coupled to an optical fiber, so that a set of interchangeable "drill bits" is at a surgeons disposal during a particular procedure. Optical 1S fiber S6 may be reusable or disposable, as may outlet portion S8 and handpiece S4.
With further reference to FIGS. I allCi 3A, exemplary of handpiece S4 may include a head portion 96 connectable to a distal end of body portion 64 by a neck 98.
Distal end 68 of body portion 64 is accordingly defined by a tissue end I 00 of head portion 96. Exemplary head portion 96 may be conical so that tissue end 100 has a lamer diameter than body portion 64.
Tissue end 100 provides a working surtnce or a tissue-engaging surface for positioning handpiece S4 over and against a surgical site in which a channel is to be drilled into tissue.
Exemplary head portion 96 may also have an aperture 10? formed therein.
Aperture 102 may function as a window for viewing a surgical site when tissue end 100 is placed against tissue.
Aperture 102 may also function as a vent for exl~austin~ gases which may be generated by laser 2S energy ablating tissue. AS Sh01v11 Ill FIG. I, exemplary neck 98 may be angular to enhance the positioning of head portion 96 against tissue. In this regard, neck 98 may be configured as a gooseneck with articulable joints for aSSllllllil~ and retaining a desired shape. Exemplary head portion 96 and neck 98 are preferably tubular, thereby providing an inner continuum with body portion 64 in which optical fiber S6 is receivable.
In particular procedures, it may be preferable to know where a hole has been drilled in tissue. However, the nature of the tissue or the size of the hole may render it difficult for the surgeon to determine where a hole has already been formed. Accordingly, the newly formed _ 1>_ hole drilled in tissue may be marked. In this regard, head portion 96 may include apparatus for marking where a hole has been drilled in tissue. For example, tissue end 100 may have an inking device which dispenses biocompatible ink or dye on the tissue where a hole has been formed.
The ink may be applied to the tissue through direct contact with tissue end 100 or, for example, S by spraying. Exemplary handpiece 54 may have a reservoir for storing and dispensing a colored liquid or a particulate solid to the tissue. Fluorescent material may be used to enhance visualization. Other indicia may be applied to the tissue by handpiece 54 or head portion 96 at the target site; for example, alphanumeric indicia may indicate the parameters of~the laser energy emitted from outlet 62 to form a particular hole.
With further reference to FIGS. 2A to 3B, exemplary coupling portion 66 may include a spring 104 receivable against a seat 106 formed on a distal end of collar 72, and a stop 108 disposed on a distal portion of tubular member 70. Spring 104 and stop 108 define a mechanism for controlling a position of tubular member 70 within body portion 64, and may be configured to facilitate the advancement and retraction of tubular member 70.
1S Exemplary source of laser energy S? is illustrated in FIG. 9. (_aser energy source S2 includes a laser 1 10 for generating laser energy L. Lxemplary laser energy source S2 may include a drive assembly 1 12 for operatively associating with handpiece 54 and optical fiber 56, and may also include a control unit 1 14 with a user interface 1 16. Exemplary drive assembly 112 may include a coupler 1 18 for connecting with optical fiber S6, optics 120 for modifying laser energy L as desired, and a clrive/motor 122. Exemplary coupler I 18 is associated with optics 120 for transferring laser ener';y L from laser I 10 to tl~e inlet of optical fiber S6.
Exemplary coupler 1 18 is also associated with drive/motor 120 for rotating optical fiber _56 As discussed above in reference to FIGS. 2.A and 2B, exemplary coupling portion 66 of handpiece S4 translates rotational movement of optical fiber 56 to axial movement to advance 2S and to retract outlet portion S8. Exemplary drive assembly f 12 preferably rotates optical fiber S6. For example, coupler I 18 may secure and retain a proximal end of optical fiber S6, with motor/drive 122 rotating coupler 1 18 which also rotates optical fiber S6.
Drive assembly 1 12 may rotate optical fiber S6 in a first direction, for example, as shown by arrow R, in F1G. 2A, to cause optical fiber S6 to advance axially as shown by arrow A. When outlet portion S8 reaches the desired advanced position, drive assembly I 12 may then rotate optical fiber S6 in an opposite second direction, as shown by arrow R~ is F1G. 2B, to cause optical fiber 56 to retract axially as shown by arrow B. Exemplary drive assembly 1 l2 may oscillate optical fiber S6 (that 16_ is, rotate optical fiber 56 clockwise and counterclockwise as shown by arrows R, and R~) so that outlet portion 58 reciprocates between the retracted position and the advance position.
Exemplary laser energy source 52 preferably controls when laser enemy L is emitted from outlet portion 58 of optical fiber 56. For example, control unit I 14 in association with laser 110 and drive assembly 1 12 may limit the emission of laser energy L to only when outlet portion 58 moves to the advance position. Laser energy L may then be terminated during the retraction of outlet portion 58. Alternatively, if drive assembly 1 12 is reciprocating outlet portion 58, laser energy L may be transmitted only during the advancing stroke of outlet portion 58; the emission of laser enemy L may then be terminated at the end of the advancing stroke.
The termination of laser energy L upon reaching the advanced position is preferably automatic and controlled by laser energy source 52. Alternatively, laser energy L may be terminated by a device such as a pressure sensor which determines when the distal end of outlet portion 58 advanced completely through a section of tissue, e.g., the wall of the heart.
This control of laser energy L is preferable during particular applications of tissue drill 50, which will be discussed in more detail below.
With further reference to F1G. I A, optical fiber » is preferably received within a housing 124. In addition to protecting optical fiber 56, exemplary housing 124 constrains any torsional flexing or bending of optical fiber 56 which may result from the rotation by drive assembly 112. Exemplary optical fiber 56 may include a complementary coupler 126 for connecting with coupler 1 18 of laser energy source 5?. Complementary coupler 126 preferably provides a releasable association with coupler 1 18 so ti~at other optical fibers in accordance with the present invention may be connected to laser enemy source 5?. Exemplary housing 124 preferably extends between coupler I 26 and chuck 74 of coupling portion 66 to provide integral protection of optical fiber 56 between laser energy source 52 and handpiece 54.
Exemplary laser energy source S2 may control a number of parameters of tissue drill 50, including distance d at which outlet portion 56 advances, a speed at which outlet portion 56 advances, and a level at which laser enemy is emitted from outlet 62. Control unit 1 14 in association with user interface I 16 preferably controls, programs, monitors, and/or adjusts each of these parameters depending upon a particular tissue-drilling application.
For example, one the many applications of tissue drill 50 is for drilling holes or channels into or through heart walls. This procedure is kn0\vll aS 11'Clil.1'lllJ'llL'CIl'CI~ICtI
re>>~cr.~~cmlcrni~u~iun or, n101'e Srlllply, as _ 17_ TMR. FIGS. l0A through I OD schematically illustrate an exemplary T>t1R
procedure implementing tissue drill 50 of the present invention.
A heart wall 130 is illustrated in FIG. 10.<1 and includes myocardium, or heart muscle, 132 positioned between an outer serous layer or epicardium 134 and an inner membrane or S endocardium 136. It has been found to be medically beneficial to revascularize the myocardium of patients suffering from severe ischemic carcliomyopathy. The revascularization of tloe myocardium 132 involves forming new channels in the tissue. f3y implementing exemplary tissue drill 50 of the present invention, new channel may be formed in the myocardium in a controlled, consistent, and pCOgrammable Illallller.
Prior to a TMR procedure, the level at which laser I 10 is to generate laser energy (_, and the frequency at which laser energy L is to be pulsed may be determined. 111 addulon, distance cm at which outlet portion 58 is to advance beyond distal end 68 and the speed at which outlet portion 58 is to rotate may be determined. These parameters may be stored In COlltrol unit 1 14 and varied or programmed via user interface 1 16.
During the TI~IR procedure, access to the patient's chest cavity is provided, preferably by a minimally invasive procedure such as an intercostal incision using trocar sheaths. Access to the patient's heart is then provided, for example, by incising the pericardium. With outlet portion 58 in the retracted position, a surgeon may then maneuver head portion 96 of handpiece 54 into the chest cavity and position tissue surtace 100 against the epicardium 134, as shown in FIG. 10A. As discussed above, outlet portion SS may project slightly beyond distal end 68 (that is, tissue end 100) when in the retracted position to provide the surgeon with a tactile feel of the position of end surface 60 on the epicardium I 3=1.
V~~hen in the desired position on the epicardium 134, tissue drill 50 may be activated.
This activation may be accomplished manually by an assistant via user interface 1 16 or by the surgeon with a foot or a hand trigger. Alternatively, activation of tissue drill 50 may be synchronized with the electrical activity of the heart through the use of an electrocardiogram (EKG) machine. Activation of tissue drill 50 causes laser energy source 52 to generate and transmit laser energy to optical fiber SG. Activation also causes optical fiber 56 to rotate anti advance outlet portion 58 through the epicardiunl I 34 and into the myocardium 132 of the heart wall 130, as shown in FIG. 1013.
Outlet portion 58 continues to advance through the nlyOCardlUlTl 132 and throu~~h the endocardium 136. Vhhen end surface GO of outlet portion 58 has advanced throu~,h the 18_ endocardium 136 and is positioned within the left ventricle of the patient's heart aS shown 111 FIG. l OC, the emission of laser enemy is preferably terminated, and the outlet portion 58 is retracted. A new channel 138 through tl~e heart mall 1 30 results from this procedure as shown in FIG. 10D. Oxygenated blood from the lest ventricle may enter the new channel I 38 through the endocardium 136 and perfuse the tissue of the myocardium 132 surrounding the new channel 138. When handpiece 54 is configured as a catheter, outlet portion 58 advances through the endocardium 136 and then into the nl)~OClrdll1111 f 32. Because outlet portion 58 may be programmed to advance a predetermined distance, outlet portion 58 may either continue to advance completely through the epicardium 1 34 or begin to retract the predetermined distance within the myocardium 132, thereby forming a hole in the heart wall 130 rather than a channel through the heart wall 130.
As mentioned above, reduced trauma to tl~e myocardium 1 34 surroundinv; the new channel 138 results from the eccentric relationship between outlet 62 and rotational axis E. Tlris reduced trauma may enable the surrounding tissue to regenerate vascular tissue from the new channel 138 and into the myocardium 1 34 or to experience angiogenesis. In addition to the eccentricity of outlet portion 58, the level oi~trauma inflicted on the surrounding tissue is mediated by the level of laser enemy emitted ti~om outlet 62, which will now be discussed.
With reference to FIG. 9, the energy level at wlricl~ laser energy I. is generated and transmitted to optical fiber 56 may be varied, pro<~rammed, and controlled according to each tissue-drilling application. For example, tissue drill 50 nay be configured for drilling holes in all types of animal tissue and plant tissue, as well as other substances. The parameters which define the characteristics of laser ablation include frequency, energy her channel, pulse width, and pulse rate. As mentioned earlier, ablation is a process of~breal:in~ bonds between atoms in molecules by adding energy to the molecules. One preferred level oftlre laser energy L
for TMR
applications is to limit tl~e energy her pulse to less thall about 100 milliJoules per square millimeter of area (mJ/mm~). l~lore preferably, an energy per pulse of about 30 I11J/IlllllZ has been found to ablate cardiac tissue at a substantially reduced level of trauma. Tlre energy per pulse of laser 1 10 may be varied according to specific tissue-drilling procedures.
With fiWher reference to FIGS. 3A and 3B, the drive may be configured to control the rate at which outlet portion 58 advances and retracts The rate of advancement is controlled by the speed at which optical fiber 56 rotates and the pltCll Of~tllf: COlllplelllelltaly tlll-eildln~ of collar 72 and tubular member 78. For smooth and continuous operation, it has been determined that optical fiber 56 and, accordingly, outlet portion 58 should rotate at a speed under about 5,000 revolutions per minute (RPM). For TMR applications oftissue drill 50, a rotational speed ranging from about 1,000 RPM to about 2,000 RPM is preferred. In this regard, a specific TMR
configuration of tissue drill 50 may be as follows. Optical fiber S6 may rotate at about 1,340 RfM. The pitch of threading 76 and 78 may be configured so that outlet pol-tion 58 advances at a rate of about 15.5 millimeters per second (mn~/s). With a rotational speed of 1,340 RPI\-1, it takes about 46 milliseconds (ms) for outlet portion 58 to complete one rotation. For TMR applications, laser 1 I 0 may emit pulses of laser energy L of about ?0 nanoseconds (ns) in duration, with each pulse being separated by about 4 ms.
The pulse rate may be about 10 pulses per revolution (or at about every 36° of rotation) or about 240 pulses per second.
Rather than advallClllg and retracting outlet portion SS at a constant rate as described above, tissue drill 50 may be configured such that outlet portion 58 moves at varying rates of speed between the retracted and advanced positions. The slower outlet portion 58 advances (or retracts) while emitting laser energy L, the more tissue that becomes ablated because the tissue is subject to more laser energy over time. Accordingly, a hole may be formed with a diameter greater than diameter d~, of end surface 60 (and outlet pol-tion 58) by aclvanclng outlet pol-tion 58 at a speed which allows laser energry L to ablate a greater amount of tissue. Alternatively, tile power of laser energy L may also be varied during the advancement of outlet portion S8 so that the tissue is subjected to more or less laser energy L. Generally speaking, a surgeon may program tissue drill 50 to ablate tissue at varying levels of enerV~y per unit time to form holes of varying desired diameters or configurations.
The energy per unit time may be adjusted by varying either the speed at which outlet polrtion 58 advances (which varies the time the tissue is subject to laser energy) or the level of laser energy, or both.
In order to form the substantially cylindrical hole 138 shown 111 FIG. l OD, tissue drill 50 ?5 advanced outlet portion 58 at a substantially constant speed, and laser energy source 52 emitted laser energy at a substantially constant level. However, if a conical-shaped hole 140 as S110wn Ill F1G. I 1 is desired, with the apes: of the hole 140 positioned at the epicardium I 34 and the base of the hole 140 positioned at the endocardium 136, then tissue drill 50 may be configured to advance outlet portion 58 at a decreasing rate (i.e., moving at a slower and slower speed) ve~hile advancing through the heart wall 130 from the epicardium 134 to the endocardium I 36.
Accordingly, a greater amount of tissue is ablated as outlet pol-tion 58 advances at a slower speed The resulting hole 140 has a diameter substantially equal to diameter d" ofoutlet portion S8 at the epicardium 1 34 and a diameter larger than diameter d~s at the endocarciium 136. By fornung the hole 140 with a relatively lame diameter at the endocardium 136 improves the patency of the hole and, therefore, the perfusion of the blood into the myocardium 132. In addition, by forming a hole with as small a diameter as possible at the epicardium 134 minimizes bleeding and trauma.
With reference to FIG. 12, another noncylindrically shaped hole 142 is shown.
Rather than forming hole 142 by advancing outlet portion 58 fi-om the epicardium 134 to the endocardium 136 as shown in FIG. I I, hole 142 is formed endovascularly, with outlet portion 58 advancing from the endocardium 136 and into the myocardium 132 a predetermined distance c/. As mentioned above, to form holes endovascularly, handpiece 54 may be conti~,ureci as a catheter, with access to the left ventricle of the heart provided through, for example, a femoral arrtery and the aolrta. To form hole 142 with a diameter greater than diameter d~, of end surfirce 60 at tire endocardium 136, tissue drill 50 is configured to advance outlet portion >8 relatively slowly at or near the epicardium I 36 and then to increase the speed. This results in more tissue being ablated at or near the endocardium 136 tllall at the ~~170tt0111~~ of hole 142 wit111I1 tile illyOCa1'dllllll I32. LaSel-energy may also be emitted whole 1 S outlet portion 58 retracts to ablate more tissue toward the endocardium 136. The speed of advancement may be varied by varying either the revolutions per second at which outlet portion 58 rotates or the pitch of threading 76 and/or 7S, or both. As mentioned above, rather than varying the speed at which outlet polrtion 58 advances, the level of emitted laser energy I_ may be varied. In this regard, to form hole 142, tissue drill 50 may be configured to emit laser energy L at a relatively Nigh level when outlet polrtion SS begins to advance, and then to decrease the level as outlet portion S8 advances distance c/.
Alternatively, rather than adJustrng the speed or the enemy level, outlet portion 58 may reciprocate a multiple of times either at increasing depths or at decreasing depths. For example, referencing FIG. 12, if the desired depth of tire hole to be formed is distance cl (that is, the distance end surface 60 advances beyond the distal end ofhandpiece 54), then tissue drill 50 may be configured to advance outlet portion 58 a distance cl on a first stroke and then to advance outlet portion 58 a distance which incrementally decreases for each subsequent stroke for a predetermined number of strokes. Accordingly, even though the speed at which outlet portion 58 advances and the level at which laser energy L is emitted, hole 142 Illay be formed with a relatively large dlallleter at the endocardium 136 and tapered toward the epicardium l34 because tissue toward the endocardium 134 is subject to repeated laser enemy with the multiple strokes of outlet polrtion 58. Therefore, a greater portion of this tissue is ablated because of the increased level of energy received per unit time.

Alternatively, rather than decreasing the distance of the stroke, the distance of each multiple stroke may be incrementally increased to form hole 140 of F1G. 1 1. In addition, if it is desired to form a hole with a relatively large-diameter inner chamber, then tissue drill 50 lay pause outlet portion 58 at a predetermined distance for a predetermined amount oftime to concentrate laser energy at one location to ablate a relatively large portion of tissue at that location.
Delivery of Medicament to Tissue An exemplary system for delivering medicament to tissue which is configured in accordance with the present invention is illustrated in FIG. 13. Exemplary medicament delivery system is referenced with numeral l 50 and may be utilized to form a hole or channel in tissue, for example, cardiac tissue (nryocardium), and then to deliver medicament, for example, a therapeutic agent for the treatment of cardiovascular disease, or a growth factor, to the tissue by partially or fillly filling the hole or channel with tile medicament, by injectin~~ n~eciicament into the tissue surrounding the hole or channel, or by administering medicament to a region which includes the hole or channel anti the surrounding tissue. This process may be repeated to form and fill a plurality of holes and channels in a targeted area of tissue. In contrast to conventional systemic delivery approaches, the system I 50 of the present invention delivers medicament in a controlled manner to specific targeted tissue. The terms lmle and clmmue~l used herein indicate any space formed in tissue or through a section of tissue, which space may be substantially re~mllar i1 shape, such as circular, elliptical, curvilinear, or rectilinear, or SIIbStalltially irregular IIl shape.
The exemplary embodiment of delivery system 150 illustrated in F1G. 13 forms the holes or channels by removing tissue with laser ablation. As mentioned above, it has been found that tissue ablation with laser energy StlrlllllateS a llatlll'al b1010~ICaI prOCeSS Of illl~lO~eIIeSIS I11 the heart. In addition, angiogenic-enhancing growth factors have been found to promote angiogenesis in the hear Accordingly, a synergistic stimulation and promotion of angiogenesis in the heart is created by augmenting the bean's natural angiogenic response to laser ablation with tl~e delivery ofgroWh factor to those areas of the myocardium which soave been ablated. The coupling of the heal-t's natural response to the f01-lllatl0rl Of CllallilelS \'Vlth the delivery of angiogenic growth factor into or adjacent to those channels provides a benefit to patients not possible prior to the present invention.
~9edicament delivery system 150 may include many Of the 51111e elelllelltS aS
eXelllplaly tissue drill 50 discussed above. Elements of medicament delivery system I 50 which are substantially analogous to elements of tissue drill 50 use like reference numerals with the addition of a prime (').
For example, IlledICalllelll delivery system 150 includes a handpiece S=I' V~lllCll Illay be S1117Sta11t11IIy 77 _ the same as handpiece 54 of tissue drill 50. 'fliis referencin g convention will be used in the description hereunder, and the earlier description of such analogous elements will not be repeated in connection with medicament delivery system I 50.
In cardiac applications of the system 150 of tl~e invention, the administration of medicament such as endothelial growth factor to cardiac tissue such as myocardium promotes cardiovascular angiogenesis. Growth factors are proteins that stimulate or enhance cell growth. Growtlrfactor proteins may be packaged in carrier molecules to specifically enhance angiogenesis. For example, the naked DNA of the growth-factor pl'otelll may be COlllbllled with a cellular matrix. Examples of cellular matrixes include fibrin, plasma, and ally other stnlcture that enhances the biocompatibility of the growth factor in the tissue, the angiogenic activity of the growth factor, and/or the sustained release of the growth factor into the tissue. There are many commercially available growth factors that promote angiogenesis, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming ~;rowtl~ factor-beta (TGF-(3), and platelet-derived growth factor (PDGF). The term nmc~iccrrncm~ used herein may include growth factor alone, growth factor in combination with a cellular matrix, or growth tractor In COn1b111i1tI0n wlth any other component that is known to assist in the delivery of the growth factor. In addition, IlledICalllent could include any other substance that stimulates angiogenic activity in the heart.
To deliver medicament to myocardium, exemplary medicament delivery system 150 includes a tissue-removal device for forming boles or channels in tissue, such as a source of laser energy and medicament 152 and an ablatin'; and injecting device 154. As discussed in more detail below, ablating and injecting device 154 includes an optical fiber which receives laser energy tl'Olll SOUI-Ce 152 for ablating tissue to form a channel, and a delivery member which receives medicament from source 152 for injection into the channel. In cardiac applications, system I
50 is able to deliver growth factor directly into the ischemic myocardium of a patient to promote the grova~th of endothelial cells.
With additional reference to FIGS. 1=! and I 5, exemplary ablating and injecting device ) S4 may include an optical fiber 156 and a delivery member I 58 molded together into a unitary structure with cladding 160. As described above, exemplary optical fiber 156 may include a core S2' and a cladding 84', with core 82' having all lrllet 86' for receiving laser energy and outlet 62' for emitting laser energy, as indicated by arrow L in F1G. 13. Exemplary delivery member 1 S8 may include a wall 162 in v.vhich is defined a lumen I 64 with an inlet 166 for receiving medicament and an outlet 168 for providing medicament, which is indicated by arrow Nl in F1G. 13.

Ablating and injecting device 154 has an end surface 170 and an outlet portion 172. Ocltlets 62' and 168 may be substantially coplanar with end surface 170.
Referencing F1G. 16, exemplary laser energy and medicament source 152 may include a laser 110', a drive motor 112', a control unit 1 14', a user interface 116', and a coupler 1 18' as S described above. Source 152 may also include a medicament supply 174 for providing medicament 1V1 and an injection unit 176 connected to supply 174, both of which are connected to control unit 1 14'. A coupler 178 connects lines from laser optics 120' and injection unit 176 into the unitary ablating and injecting device I 54.
Analogous to optical fiber S6 described above, exemplary ablating and injecting device 154 is rotatable about an axis of rotation E and translatable betmeen an advanced position and a retracted position. With additional reference to FIGS. 17A and 17B, system 150 may form a channel 138 in myocardium 132, either partially tllrou<~h the myocardium or completely through the myocardium. In accordance with the present invention, as distal portion l72 of ablating and injecting device 154 retracts from tile advanced position to the retracted position, as shown by arrow B, control unit 1 14' activates injection unit 176 to inject medicament M from supply 174 into delivery member 158 and through outlet l68 into channel 138, as shown in FIG. 17A.
When device 154 is in the retracted position and handpiece 54' is moved away, a discrete amount 179 of medicament is left within channel 138, as shown in FIG. 17(3.
The discrete amount 179 may partially or fully till channel 135. Tioe procedure may be repeated a plurality of times at different locations in the myocardium 132, thereby seeding the myocardium with medicament such as angiogenesis-promoting ~~rowtl~ factor. Exemplary injection unit 176 may inject medicament through tile use of hydraulics, pneumatics, aerosol, or other means.
In addition, injection unit 176 may be con(i~ured as an injection jet nozzle which utilizes high pressure to create a fluid COIlllllil Of 111ed1C8111e11t for injection into tissue. A jet injector may also be used to form a hole in or through tissue with high-pressure fluid (wluch may contain medicament), either by tearing (or expanding) the tissue or by removing the tissue, or a combination of both. The jet injector may be configured to deliver medicament to tile tissue while f01-nlitl~ the hole or channel therein.
Regarding the coupling of ablating and injecting device 154 to laser energy and medicament source 152, reference is made to FIGS. 18 and 19 in which an exemplary embodiment of a coupling assembly 180 is illustrated. Exemplary coupling assembly 180 includes a housing 182 which is adapted to receive a reel 184 in a rotatable and sealed _2:~_ relationship. Reel 184 includes a passage I 86 formed axially therethrougl in which ablating and injecting device 1 S4 is securely received. Reel 184 also includes an annular channel 188 and a through hole 190 extending between passage 186 and channel I 88. Delivery member I S8 extends from device 154 into through hole 190 to be in communication with channel 188. A
feeding tube 192 extends between a port 194 of housing I 82 and the medicament injection and supply units 176 and 174.
A plurality of o-rings 196 may be used to seal reel 184 within housing 182, device I S4 within passage 186, and delivery member 1 _58 within through hole 190. Rings 196 may be low-friction Teflon'x seals. Specialized couplings, such as a Touly-Borst valve coupling, may be used to connect device 1 S4 to reel l 84. I-lousing 182 may include structure such as stops to limit the axial translation of reel 184. Altlough exa<~~,erated in tl~e drawings, tolerances between reel 184 and housing 182 may be on the order of less than about O.OOS
inch. In addition, housing 182 may be of a two-piece desi~~n with nvo halves hinged together to allow easy access to the inside ofthe housing.
Coupling assembly 180 allows ablating and injecting device I S4 to rotate about rotational axis E under power from drive unit I 12' while receiving laser energy and medicament.
For example, device 1 S4 may be driven about 40 revolutions in one direction (yielding the advanced position), and then driven about 40 revolutions in the other direction (yielding the retracted position).
Because of the secure coupling with device 1 S4, reel I 84 is driven by device 1 S4 to rotate about axis E, that is device 1 S4 may act as a drive shat. ~~~l~en it is desired to deliver medicament to tissue, injection unit 176 injects medicament tlu-ou~h tube I 92 (which is indicated by arrow M) and into a space 198 defined within channel 1 S8 and beUveen reel I 84 and Dousing I 82.
Medicament is accordingly urged and/or injected into the lumen I 64 of delivery member I S8.
It~ledicalnent may be continuously injected into delivery lumen 1 S8 while reel 184 rotates. As described above, the injection of medicament into delivery lumen 158 may be limited to when device 154 is retracting.
With general reference to FIG. 13, rather than coupling delivery member 1 S8 to medicament supply 174 at source system 152, exemplary Dandpiece _S4' may include an assembly for injecting medicament into delivery member 1 S8 (not shown). For example, a pressure capsule, such as a CO, capsule, may inject medicament into the inlet 166 o('lumen 164 and out of the outlet 168. Delivery member 158 may be coiled within handpiece S4' when in the retracted positioned, and may then uncoil while being driven to the advanced position. In the embodiment Wlth all 111)eCtloll aSSelllbly at handpiece 54', delivery member 1 S8 may have a relatively shoe overall lennh as the handpiece is positioned at or near the tissue targeted to receive medicament.
Alternative configurations of the ablating and injecting device of the present invention are shown in FIGS. 20 and 21. Referencing FIG. 20, exemplary ablating and injecting device 154' S includes an optical fiber 156' and a delivery member 158' molded together into a unitary structure with cladding 160'. Exemplary delivery member 1 SS' may be crescent shaped in cross-section, as shown. As discussed above, the diameter d" of the outlet of optical fiber 156' is preferably at least one half of the diameter d~, of the end surface 170' of device l S4'.
For example, diameter do may be about 0.6 mm and diameter d" may be abollt 1.0 mm. Accordingly, as device 154' rotates about axis E, laser energy emitted from optical fiber 156' ablates tissue along the entire radial sweep of axis E, thereby forming a channel of about 1.0 mm in diameter, which is described above (see FIG. 8).
Referencing FIG. 21, exemplary ablotiy anti injecting device I S4" includes a pair of optical fibers 156cr and 156h and a delivery member 1 SS" molded to~,ether into a unitary structure with cladding 160". Exemplary delivery member I SS" may be rectilinear shaped in cross-section, as shown. Tlle outlet of each optical fiber l S6 preferably has a diameter d" of approximately one quarter of the diameter d~, of the end surface 170" of device 154'. Therefore, collectively the diameters d~ of the optical fibers 156~r and I 56h comprise about one half of the diameter d~, of the end surface 170". For example, dian7eter d" may be about 0.3 nun and diameter cl~, of end surface 170" 177x)' be about 1.0 111171. Alterllallvely, any number of~ fibers may be used in multiple-fiber device ( 54", such as four 0. I 5-mm diameter fibers.
Optical fiber becomes more flexible when its diameter is reduced. 1t follows that the pair Of Optical fibers 1 56C1 al7d 1567 Of FIG. 2 I each W~Itll a Cliallletei' Of about 0.~ 171117 are 1770re flexible than the single optical fiber 156' of FIG. 20 with a diameter of about 0.6 mm. As such, device 154" is more flexible and is able to follow a more tortuous path than device 154'.
Accordingly, device 154' shown in FIG. 20 is useiill in direct-visualization procedures in conjunction with a handiiece as described above, such as in illtra-operative or traps-tlloraclC
procedures, which do not require the optical fiber to bend through tortuous paths. Device I 54"
shown in F1G. 21 is usefill in indirect-visualization procedures in conjunction with a catheter and a scope, such as traps-septal and endovascular procedures. For example, device 154" may be inserted into a femoral artery, through tl7e aOrtIC 11-C17, and into the left ventricle to ablate tissue from the endocardium to the epicardium.

Rather than fOrrllln~ ChaIlIlelS Ill tissue with laser ablation as described above, tissue may be removed to form channels in accordance with the present invention for medicament delivery by other methods, for example, by high-frequency electrical energy or radio-frequency (RF) energy. Referencing FIG. 22, an exemplary embodiment of a tissue-removal and medicament-delivery device 200 which uses electrical energy to remove tissue in accordance with the present invention is illustrated. Device 200 includes an electrode 202 disposed on a distal tip of the device, an insulator 204 proximal to the electrode ?0?, anti a body 20G. A
delivery lumen 208 is formed axially through electrode 202, insulator ?0-I, and body ?06, and I~as an outlet 210 in a distal end of device 200.
An alternative embodiment of an electrical-energy tissue-removal and medicament-delivery device 200' of the invention is illustrated in F1G. 2 3. Rather than having an axial delivery lumen, device 200' includes at least one delivery lumen 210 formed longitudinally through at least the body 20G'. As shown in FIG. 2 3, two delivery lumens ?
l2cr and 21?h are formed through the body 206' and extend into the insulator 204'. Each lumen ?
12 has an outlet 214 formed on a side 216 of device 200'. In the exemplary embodiment, outlets 214n and 214h may be substantially diametrically opposed within the device. Alternatively, each lumen ? 12 may have a plurality of outlets which form an array of ports on the side 216 of device 200' .
With additional reference to FIG. 2=4, in use, tl~e tissue-removal and medicament-delivery devices 200 and 200' generate high-frequency electrical enemy, which in turn generates an ionized plasma corona ? 16 and converts tissue 1 32 to gas to create a channel or hole in the tissue. A ground plate 21 S ma~~ be provided such that tissue 132 is positioned between the ground plate and electrode 202. '1'I~e ground plate 218 may be used to control conduction paths (shown by the dashed arrows) formed by tl~e positively charged electrode 202, v.vhich controls the formation of channels in tissue. After holes or channels are formed in tissue, medicament such as growth factor that promotes angiugenesis may be delivered to the tissue within the hole or channel itself via the delivery lumen as described above. Alternatively, with reference to FIG.
25, medicament may be delivered into the walls of the hole or channel 138 and into the tissue 132 surrounding the hole or channel 138 via tl~e delivery lumens ? 12, as indicated by arrows 1~~1.
Referencing FIG. 26, another exemplary embodiment of an electrical-energy tissue-removal and medicament-delivery device 200" of tile invention is illustrated.
Device 200"
includes a cathode 220 disposed on a distal tip of tl~e device, an InSrllatOr 204" proximal to the electrode 202, an anode 222 proximal to the insulator, and a body 206". A
delivery lumen 208 is formed axially through the device 200". Electrical-conducting leads (not shown) connect the cathode and anode 220 and 222 to a power source. When activated, conduction paths (shown in dashed lines) between the cathode 220 and the anode 220 define the ionized plasma cornea 216' which converts tissue to gas to form channels.
S Another exemplary embodiment of a medicament-delivery system 230 of the present invention is illustrated in FIGS. 27, 28, and 29. System 230 includes an ablating and injecting device 232 received within a catheter 234. Exemplary ablating and injecting device 232 includes a pair of optical fibers 236a and 236h and a pair of delivery members 238a and 238h. Cladding 240 configures the fibers 236 and 238 into a unitary and cylindrical device.
Optical fibers 236 and delivery members 238 may be configured and function in accordance with the description provided above. Exemplary device 232 also includes rifling tracks 242 formed on an annular lip 244 thereof, preferably at a distal end of the device, and exemplary catheter 234 111C1lIdeS rifllllg 246 formed on an inner surface thereof for slidingly engaging with the rifling tracks 242 of the ablating and injecting device 232. Accordingly, as ablating and injecting device 232 rotates, the rifling 246 translates the device 232 axially within catheter 234, between the advanced and retracted positions as described above.
Exemplary medicament-delivery system 230 is particularly useful in endovascular procedures which may entail guiding the ablating and injecting device 232 and catheter 234 through tortuous paths to its final destination. Accordingly, it is preferable to maximize as much as possible the flexibility of the ablating and injecting device 232. As such, it is preferable for the diameters of the optical fibers 236 to be as SIllaIl as possible while still capable of carrying sufficient laser energy to ablate tissue. In a preferred embodiment, the diameter of each optical fiber 236 may be about 0.25 nun. The overall diameter of the device 232 nay then be about 0.5 mm.
In an alternative embodiment of the ablating and injecting device of tile present invention, the medicament may be delivered directly to the tissue surrounding the channel instead of delivering the medicament into tile channel or into the tissue by way of tile channel.
This may be advantageous where it is desirable to avoid systemic administration of the medicament, which could occur through washout of medicament when it is delivered directly into the channel. Various configurations of this alternate embodiment are shown in FIGS. 30-40.
_2S_ Referencing FIG. 30, alternate head portion 100' Ilas one or more needles 2S0 on tire outer rim of its tissue-engaging surtace for penetrating the tissue around the perimeter of the tissue channel opening. This provides access directly to the tissue surrounding the channel. ~I'I~e delivery device is provided with one or more medicament lumens 164' which are in fluid communication with needles 250. Needles 2S0 pierce the tissue around the perimeter of the channel opening and deliver medicament by way of lumen or lumens 164'. The medicament diffuses through the tissue without having to enter into the channel, thus avoiding 111ed1Calllen2 washout and the possibility of systemic delivery of tile medicament. F1G. 31 illustrates the end surface of head portion 100' having an array of needles 2S0 around its perimeter. FIG. 32 illustrates medicament 2S2 diffusing into the tissue surrounding channel 138.
Other embodiments of alternate head portion 100' are illustrated in FIGS. 33 and 34.
FIG. 33 illustrates head portion 100' having a IloZZle Or ilOZZIeS 2J=1 around its perimeter. Nozzles 2S4 are adapted to atomize tile medicament when head portion 100' is placed up against the tissue surrounding the channel opening. As in the previous embodiment using needles 250, the 1S medicament is diffused directly into the tissue and not into the channel where it can be washed out into the patient's system. F1G. 3=4 illustrates yet another embodiment wherein head portion 100' has a port or ports 2S6 on the head portion perimeter for diffusing medicament directly into the tissue surrounding the channel opening.
FIGS. 3S and 36 illustrate that medicament can be provided to head portion 100' through a single lumen 164" which is in tluid CO IllIl111111cat1011 wltll all 811rllllilr lllallltold 2S8 Wh1C17 c01T11111Ir71CateS throu~.~h the perimeter ofhead portion 100' to ports 256. F1G. 37 illustrates an alternate embodiment wherein single lumen 16=I" Iras an annular geometry. Those skilled in the art will appreciate that this sin<,le lumen embodiment incorporating manifold 2S8 can also be utilized with nozzles 2S4 or needles 250. Similarly, it will be appreciated by those skilled in the ao that other means for diflusin~, medicament directly into the tissue surrounding the channel opening can be utilized for like effect.
FIG. 38 illustrates yet another exemplary embodiment wherein at least one delivery lumen 264 is in fluid communication with delivery outlet 266 and at least one vacuum lumen 268 is in communication with a vacuum source (not shown) and terminates in vacuum outlet 270. By providing a vaCllllill to head portion 100' through lumen 268 to outlet 270 the clinician can insure that medicament Catl be delivered directly to the tissue through lumen 264 and outlet 266. It will be appreciated by those skilled in the art that this embodiment could include a _2c~_ plurality of vaclllllll 1r1111eI1S alld a plurality of delivery llllllellS t0 nrax11111Ze the effectiveness of the invention.
Referencing F1G. 39, an alternate excnrplary embodiment of an electrical-enemy tissue-removal and medicament-delivery device 200" is illustrated wherein the medicament can be directly delivered into the tissue walls and dit~used into the tISSlle Slll'rolltldlilg the channel. As in the embodiment of FIG. 23, two delivery lumens 212a' and 212b' are provided, each having its respective outlet 214x' and 214b'. In tire exemplal>> embodiment, outlets 214a' and 214b' may be substantially diametrically opposed mitlrin the device. In this embodiment, vacuum lumens 212c' and 212d' are provided longitudinally through the body of device 200" and in communication with outlets 214c' and 214d', respectively. Outlets 214c' and 214d' may also be diametrically opposed to each other. Vacuum lumens 212c' and 212d' are in communication with a vacuum source (not shown) which provides a vacuum through lrlnrens 212c' and 212d' to outlets 214c' and 214d' to drav.v the tissue channel wall up against outlets 2 I 4c' and 214d'. Due to their proximity, sufficient vacuum can be provided to also draw the tissue wall up against I S outlets 214a' and 214b'. Medicament 252 can then be provided through delivery lumens 212x' and 212b' to outlets 214x' and 214b' and directly into the tissue wall of the channel as illustrated in FIG. 40. In the embodiment shown, outlets 21=la' alld 21=4b' are distal to outlets 214c' and 214d'. However, it is also possible to configure the outlets so that 214c' and 214d' outlets are distal to 214a' and 214b' outlets and to confl<,ure the delivery and vacuum lumens accordingly.
As is the case with the embodiment of FIGS. 30-s~, IIrIS elllbodlillellt also pel'ilrltS IlledICalllellt to be diffused into tire tissue surrounding tire channel without having systemic washout of tire medicament.
In addition to removin '; tissue to form boles or channels by laser ablation or by high-frequency electrical enemy, holes or channels may be formed in tissue mechanically with hot tips or biopsy needles, ultrasonically, or hydraulically with high-pressure water. The medicament call be growth factor, which may take many forms. For example, ,rowtlr factor may be delivered as a protein solution. Alternatively, ~;rov.~~th factor may be combined with a fibrin, collagen, or plasma to form a cellular matrix gel. Growrth factor may also be mixed into a semi-solid using a biocompatible matrix. Further, growth factor may be delivered to tissue in an atomized form under pressure. Tlre medicament can also be a gene drat encodes for said <~rovvtlr factor, or any other therapeutic ajent or gene therapy agent that promotes an~;iolenesis or any therapeutic agent for the treatment of cardiovascular disease. Whatever the form may be, the angio~enesis-promoting _;0_ growth-factor solution is administered throu~fh the delivery lulnen(s) to enhance and accelerate the angiogenic process. The gro\vth factor solution may be driven into the channel and/or tlSSlle LISIIIs, for example, a pnet1111at1C SyStenl, a IlleC11a111Ca1 S~'SlClll (t;.~;., a syringe-type system witll a plunger), a hydraulic system (e.g., using fluids or gas), or a gravitational system.
Those skilled in the art will understand that the embodiments of the present invention described above exemplify the present invention and do not limit the scope of the invention to these specifically illustrated and described embodiments. The scope of the invention is determined by the terms of the appended claims and their legal equivalents, rather than by the described examples. In addition, the exemplary embodiments provide a follildall011 f1~0r11 \\'111C11 llllnlerollS alterllatlveS alld I~ 1170d1fiCat10T1S May be n lade, which alternatives alld IllOC11f1C1t1011S
al'e aISO \\'itlllll tile SCOpe Oftlle present invention as defined in the appended claims - J I -

Claims

What is claimed is:

1. A medicament delivery system comprising:
A) a laser source for providing laser enemy;
B) a medicament source for providing medicament;
C) an ablating and delivering device including:
(1) an optical fiber having:
(a) a distal portion;
(b) an inlet end for coupling to said laser source; and (c) an outlet end disposed at said distal portion for emitting laser energy;
and (2) a delivery member leaving:
(a) a lumen;
(b) a distal portion;
(c) an inlet end for coupling to said medicament source; and (d) an outlet end disposed at said distal portion for injecting medicament;
and D) a handpiece which receives said ablating and injecting device in controlled, movable relationship thereto.

2. A medicament delivery system as claimed in claim 1 wherein said ablating and injecting device further includes cladding disposed about said distal portions of said optical fiber and said delivery member, thereby forming an integral distal portion of said ablating and delivering device.

3. A medicament delivery system as claimed in claim 2 wherein said handpiece reciprocates said distal portion of said ablating and injecting device between an advanced position and a retracted position.

4. A medicament delivery system as claimed in claim 3 further comprising a control unit connected to said laser source and said medicament source.

5. A medicament delivery system as claimed in claim 4 wherein said control unit activates said laser source to emit laser energy when said distal portion of said ablating and injecting device moves from said retracted position to said advanced position.

6. A medicament delivery system as claimed in claim 5 wherein said control said control unit activates said medicament source to inject medicament when said distal portion of said ablating and injecting device moves from said advanced position to said retracted position.

7. Apparatus for use in delivering medicament to tissue, comprising:
an ablating and delivering device including:
(1) an optical fiber having:
(a) a distal portion;
(b) an inlet end for coupling to a laser energy source; and (c) an outlet end disposed at said distal portion for emitting laser energy;
and (2) a delivery member having:
(a) a lumen;
(b) a distal portion;
(c) an inlet end for coupling to a medicament source; and (d) an outlet end disposed at said distal portion for providing medicament.

8. Apparatus as claimed in claim 7 further comprising a handpiece which receives said ablating and delivering device in controlled, movable relationship thereto.

9. A method for delivering medicament to tissue, said method comprising tile steps of:
providing access to tile tissue;
forming a channel in the tissue by removing tissue; and providing medicament in said channel and/or in tissue surrounding said channel.

10. A method as claimed in claim 9 wherein said forming step comprises the step of ablating the tissue with laser energy.

11. A method as claimed in claim 9 wherein said forming step comprises tile step of:
converting the tissue to gas with high-frequency electrical energy.

12. A method as claimed in claim 9 wherein said step of providing medicament comprises the step of:
providing growth factor.

13. A method as claimed in Claim 12 wherein said step of providing growth factor comprises the step of:
providing growth factor combined with a cellular matrix.

14. A method as claimed in claim 12 wherein said step of providing growth factor comprises the step of:
providing growth factor combined with fibrin.

15. A method as claimed in claim 12 wherein said step of providing growth factor comprises the step of:
providing growth factor combined with collagen.

16. A method as claimed in claim 12 wherein said step of providing growth factor comprises the step of:
providing growth factor in an atomized form.

17. An method as claimed in claim 9 wherein said step of providing medicament comprises the step of:
providing medicament pneumatically.

18. A method as claimed in claim 9 wherein said step of providing medicament comprises the step of:
providing medicament hydraulically.

19. A method as claimed in claim 9 wherein the tissue is myocardium;
said forming step comprising the step of forming a Channel completely through the myocardium.

20. A method as claimed in claim 9 wherein the tissue is myocardium;

said forming step comprising the step of forming a channel partially through the myocardium.

21. A method as claimed in claim 9 wherein said step of providing a medicament comprises the step of:
providing a medicament to tissue surrounding said channel.

22. A system for delivering medicament to tissue, comprising a tissue-removal device for forming a channel in the tissue;
a delivery member for delivering medicament to and/or adjacent to said channel, said delivery member including a lumen with an inlet for receiving medicament and an outlet for providing medicament; and a handpiece that receives said delivery member so that said outlet is positionable to deliver medicament to said channel.

23. A system as claimed in claim 22 wherein said tissue-removal device includes an optical fiber.

24. A system as claimed in claim 22 wherein said tissue-removal device includes an electrode for emitting high-frequency electrical enemy.

25. A system as claimed in claim 22 further including cladding for forming said tissue-removal device and said delivery member into a substantially unitary structure.

26. A system for delivering medicament to tissue, comprising:
a tissue-removing mechanism which removes tissue to form a channel in the tissue; and a delivery conduit mechanism which moves medicament from a source to said channel.

27. A system as claimed in claim 26 wherein said tissue-removing mechanism removes tissue with laser energy.

28. A system as claimed in claim 26 wherein said tissue-removing mechanism removes tissue with electrical enemy.

29. A system as claimed in claim 26 wherein said delivery conduit mechanism includes a lumen with an inlet for receiving medicament from a source and an outlet for providing medicament to said channel.

30. A method for delivering medicament to tissue, said method comprising the steps of:
selecting tissue to receive medicament;
accessing the selected tissue;
stimulating a natural response in the selected tissue; and providing medicament to the selected tissue.

31. A method as claimed in claim 30 wherein said selecting step comprises the step of:
selecting cardiac tissue.

32. A method as claimed in claim 31 wherein said selecting step comprises the step of:
selecting ischemic cardiac tissue.

33. A method as claimed in claim 32 wherein said stimulating step comprises the step of:
stimulating an angiogenic response in the ischemic cardiac tissue.

34. A method as claimed in claim 33 wherein said providing step comprises the step of:
providing growth factor to the cardiac tissue.

35. A method as claimed in Claim 31 wherein said stimulating step comprises the step of:
ablating the selected tissue with laser energy.

36. A method as claimed in claim 35 wherein said ablating step comprises the step of:
ablating the selected tissue to form a hole or channel therein.

37. A method as claimed in claim 36 wherein said providing step comprises the step of:
providing medicament to said hole or channel.

38. A method as claimed in claim 36 wherein said providing step comprises the step of:
providing medicament to tissue surrounding said hole or channel.

39. A method as claimed in claim 31 wherein said stimulating step comprises the step of:
subjecting the selected tissue to high-frequency electrical energy.

40. A method as claimed in claim 31 wherein said providing step comprises the step of:
providing growth factor.

41. A medicament delivery system comprising:
an energy source for providing enemy to remove tissue;
a medicament source for providing medicament to the tissue;
an energy transmitting member having a an inlet end for coupling to said energy source and an outlet end disposed at a distal portion for emitting energy;
a medicament delivery member having:
an inlet end for coupling to said medicament source;
at least one lumen through said delivery member for delivering medicament;
a distal portion terminating in a tissue-engaging surface having ports in fluid communication with said lumen for injecting medicament directly into the tissue; and a handpiece which receives said enemy transmitting member and said medicament delivery member.

42. The medicament delivery system of claim 41 wherein said tissue-engaging surface further comprises one or more needles in fluid communication with said lumen for piercing the tissue and injecting medicament directly into the tissue.

43. The medicament delivery system of claim 41 wherein said tissue-engaging surface further comprises one or more nozzles in fluid communication with said lumen for injecting medicament directly into the tissue.

44. The medicament delivery system of claim 41 wherein said energy source comprises a source of laser energy and said energy transmitting member comprises an optical fiber.

45. The medicament delivery system of claim 41 wherein said energy transmitting member comprises an electrode tier emitting high-frequency electrical energy.

46. A medicament delivery system comprising:
an energy source for providing energy to remove tissue;
a medicament source for providing medicament to the tissue;
a vacuum source for providing vacuum to the system; and an energy transmitting and medicament delivery member having a all inlet end for coupling to said energy source, said medicament source and said vacuum source and an outlet end disposed at a distal portion for emitting energy and delivering medicament;
said energy transmitting and medicament delivery member further comprising:
at least a first vacuum lumen in communication With Said vacuum source and at least a first medicament delivery lumen in fluid communication with said medicament source; and at least two ports proximal to said distal portion and in close proximity to each other, comprising at least a first vacuum port in fluid communication with said vacuum lumen for providing vacuum to the tissue and at least a first delivery port is in fluid communication with said medicament delivery lumen for injecting medicament directly into the tissue.

47. The medicament delivery system of claim 46 further comprising:
a second vacuum lumen in communication with said vacuum source;
a second medicament delivery lumen in fluid communication with said medicament source;
a second vacuum port in fluid communication with said second vacuum lumen for providing vacuum to the tissue; and a second delivery port in fluid communication with said medicament delivery lumen for injecting medicament directly into the tissue.

48. The medicament delivery system of claim 47 wherein said delivery ports are substantially diametrically opposed to each other on the delivery member.

49. The medicament delivery system of claim 47 wherein said vacuum ports are substantially diametrically opposed to each other on the delivery member.

50. The medicament delivery system of claim 46 wherein said energy transmitting and medicament delivery member further comprises a distal portion having a tissue-engaging surface wherein slid lumens and said ports terminate for providing vacuum and medicament delivery to the tissue.

51. A medicament injection unit comprising:
an injection jet nozzle;
a medicament source for providing medicament to the tissue and in fluid communication with said nozzle; and a pressure source in fluid communication with said nozzle and said medicament source.

52. A method of delivering medicament to tissue, said method comprising the steps of, providing an injection jet nozzle coupled to a source of fluid and coupled to a source of medicament;
delivering said fluid through nozzle with sufficient pressure to form a hole in or through the tissue;
providing a source of high pressure between said source of medicament and said jet nozzle to create a fluid column of medicament for injection into the tissues;
and delivering medicament to the tissue through said jet nozzle.

53. A method of delivering, medicament to tissue, said method comprising the steps of;
providing an injection jet nozzle coupled to a source of fluid and coupled to a source of medicament;
providing a source of high pressure between said source of medicament and said jet nozzle to create a fluid column of medicament for injection into the tissues;

delivering said fluid through said nozzle with sufficient pressure to form a hole in or through the tissue while delivering medicament to the tissue through said jet nozzle to the tissue.

54. A method of delivering medicament to tissue, said method comprising the steps of:
providing access to the tissue;
forming a channel in the tissue by removing, tissue; and providing medicament directly to the tissue surrounding said channel.

55. The method of claim 54 further comprising the step of providing medicament directly to the tissue surrounding the opening of the channel.

56. The method of claim 55 further comprising the step of piercing tile tissue surrounding the opening of the channels and injecting medicament into the tissue.

57. The method of claim 54 further comprising the step of providing medicament directly to the tissue surrounding said by delivering medicament directly to the tissue comprising the channel wall.