CA2378250A1

CA2378250A1 - Gene therapy platformed needle and method of administering a therapeutic solution to a heart

Info

Publication number: CA2378250A1
Application number: CA002378250A
Authority: CA
Inventors: Todd K. Rosengart; Ronald G. Crystal
Original assignee: Cornell Research Foundation Inc
Current assignee: Individual
Priority date: 1999-08-05
Filing date: 2000-08-04
Publication date: 2001-02-15
Also published as: EP1199992A1; AU6521500A; WO2001010315A1; WO2001010315A9

Abstract

The invention provides a device for the delivery of a therapeutic solution, in particular, an angiogenesis-promoting substance into a heart. The device includes an elongated needle (10) having a stop, or platform (44), spaced fr om the distal needle tip (42) to limit the depth of penetration and stabilize t he needle in the cardiac tissue. The elongated needle body (30) is flexible enough to maneuver around thoracic and cardiac geometry, yet sufficiently rigid to facilitate such maneuvering. This minimally invasive procedure allo ws for delivery of the solution "at a distance" through small incisions.</SDOAB >

Description

GENE THERAPY PLATFORMED NEEDLE AND
METHOD OF ADMINISTERING A
THERAPEUTIC SOLUTION TO A HEART
FIELD OF THE INVENTION
The invention relates to devices and methods for delivering a therapeutic solution to the heart, and more specifically to a needle and a method for delivering an angiogenic substance into a beating heart.
BACKGROUND OF THE INVENTION
There have been numerous recent advances in therapies such as angioplasty and coronary bypass surgery, which are now commonly used in the treatment of ischemic heart disease. There still exist a significant number of patients for whom these conventional therapies are not feasible options in a number of circumstances.
For example, conventional coronary bypass surgery is not a treatment option in patients with diffuse small vessel coronary artery disease due to the small size and large number of diseased vessel segments. Further, re-occlusion of a diseased vessel may occur despite multiple angioplastic procedures or bypass surgeries.
One promising alternative treatment for ischemic heart disease is the delivery of angiogenesis-promoting substances to the heart tissue to induce angiogenesis.
Angiogenesis is a complex biological process that results in the growth of new blood vessels within tissue. Angiogenesis is an essential process common to several normal and pathologic conditions including embryologic development, wound healing, development of neoplasms, and the like. Angiogenesis involves the disruption of vascular basement membranes, migration and proliferation of endothelial cells, and subsequent blood vessel formation and maturation.
Angiogenesis has also been induced in heart tissue for reperfusion of tissue compromised by myocardial ischemia. Several growth factors or mediators are known to elicit angiogenic responses, and administration of these mediators promotes revascularization of ischemic tissues. These growth factors are typically proteins which stimulate endothelial cell reproduction in the target tissue.
Vascular endothelial growth factor (VEGF) is one of the most specific of the known angiogenic mediators due to localization of its receptors almost exclusively on endothelial cells. Receptors for VEGF are upregulated under ischemic conditions. Accordingly, the administration of VEGF augments the development of collateral vessels and improves function in peripheral and myocardial ischemic tissue.

Delivery of VEGF remains a significant challenge. The half life of VEGF
is very short. Accordingly, the tissue must be exposed to the growth factor for a period of days. The administration of high doses of VEGF, however, is associated with hypotension.
The growth factor should be limited to the target tissue inasmuch as the systemic administration of VEGF can induce angiogenesis in tissues other than that which has been targeted, such as occult tumors, or sensitive non-diseased organs, such as the retina. This promiscuous induction of angiogenesis can cause blindness, increase the aggressiveness of tumor cells, and lead to a multitude of other negative side-effects.
The growth factor can be delivered to the target tissue through the use of indwelling catheters over a period of time. A preferred method of delivering the growth factor, however, is in the form of gene transfer, for example, by a replication deficient adenoviral vector containing the transgene coding for the growth factor. Under this method, a quantity of the adenoviral vector having the desired genetic component is delivered to the treatment area by injection in solution.
In the past, an open-chest procedure has been used to deliver the treatment solution. According to this procedure, the patient's chest is opened surgically to expose the heart. The solution containing the adenoviral vector is then delivered to the heart tissue by using a syringe to make a number of injections in a grid-like pattern, with the surgeon keeping track of the location of each injection.
U.S.
Patent Application Serial No. 09/357,010, filed July 19, 1999, which is a continuation of PCT/L1S98/01638, filed January 29, 1998, and published on July 30, 1998, as WO 98/32859, which is assigned to the assignee of the present invention, discloses a method of enhancing the level of perfusion of blood to a target tissue during such a procedure.
Once injected, the adenoviral vector causes the cells in the target tissue to produce the desired growth factor, and this growth factor production of the treated cells will continue for a period of time. Previous studies have shown the feasibility and efficacy of safe, sustained, and localized expression of angiogenesis-promoting growth factors utilizing adenoviral-mediated gene transfer therapy.
It is desirable to be able to provide the above described therapy without the necessity of performing open-chest surgery on the patient. U.S. Patent Application Serial No. 09/035,892 filed March 6, 1998, discloses an injection ~ /~-.._ t .'-_tl-w__v. . m.~, w.......~....__~._..
oeT. 26. 2001 3:~18PM LEYDIG, vOiT & MarER No. 2648w-P. 9 PCTIU900n1399 3 Sabstitute 9hveta ~~
apparatus and method for providing gene tbet'apy treatment to~ the heart or other internal organs without necessitating such open heart surgery. The device includes as elongate flexible tubular body having a hollow needle mouaited at the'distal end for delivery of the therapeutaic substance to the tissue. This arvd other currently available devices have relatively complex designs arid, accorctiagly; are ely expensive to manufacture. Fut~her, they may be difficult to manipulate around the contours of the heart and ensure stability of the needle againslt the target tissue.
Devices is the prior art that have been ttrilized for alte~;tiata purposes also have definite shortcomings. For example, U.S. Patent~5,T95,_'~26~discloses a spinal marker needle for use in cervical discectomies. The '52fi patEnit'iieedle includes a penetration restriction member and is a rigid sktuctut~e attachable toga Syiin~e.
U.S. Patent 3,477,437 similarly includes a rigid needle stractitrc'whiich ~coihprises a coil spring segment which may be attached around the needle near its tip t6 avoid advaacem;ent of the needle too fir unto the patient's lutig:'~'fliuaboth the .. 1 ~ '526 and '437 patents disclose-anaiigements which ~cvuld=iiot~easi~y be ~ '' . _.. ~_ . ~ . .~ .. . . . _. . .
_. .. ~~~ ~~ ~e contours of the heart for ptop~rvplace~ment against ttic~ . .
: ~_ target tissue. _ Capadian Patent 2241615 discloses a catheter assemb9~y for injecting "
therapeutic liquids such as DNA solutions into a patienit's~myocacdium.. The' 24 catheter assembly is a highly complex structure worth ~sri elongated gaining catliater ~ . ~ ' in which a small reservoir is disposal forward the distal end ijf ttie'cattieter. ' One ' or mare needles extend from the distal surface of the resaivoiii.'~'Ihe entire .~
reservoir may be advanced to the end of the catheter to'cause-the aecdle to penetrate the myocardium, at which time depression'vf ~a plu~ager within the 25 reservoir injects the liquid into the myocardium. Tile cathete.r~is designed to~be advanced into the heart through an artery or vein arid late the: left or right ventricai. An alternate embodiment attaches a catheter to a syringe for delivery of a solution through the catheter lumen to a needle disposed at its distal end.
The cathetac, however, tapers at its distal end such that no stabilir;ation is provided to 30 the needle during solution delivery.
AMENDED SHEET
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i i OCT.26.2001 3:18PM IEYDIG, VOI'ER~T~ "r"'R~.2648-=-P.10 PCTIUSOOrlI399 3A Subetitnte Sheets U.S. Patent 5,688,?~6 discloses a microcannula suitable for cannulation of very small blood vessels. The microcaiaaula includes an outer, flexible polyu>'eric tube with a beveled tip wherein a rigid solid trocar is positioned is the lumen to - permit manipulation of the microcatmula, In use, the tip of the solid t><ocar pierces the blood vessel and the beveled leading edge of the microca»nula then-cotrtscts and stretches the hole punctured in the blood vessefwall: ' Oio.ce placed, the~solid freest is removed and the miorncannula may be advanced unlxha shou~lder~~on the nnicrvcannula contacts the blood vessel. One end of a ligatuni:'is tied around the blood vessel, and the other is tied around the microcennula at~ove~the shoulder to hold the nucrocaanula in position. ?hus, althbugh the iniero~:ai~nula itself may be a flexible elongated structure, the freest is specifically' included to-c~alce~the device adequately stiff'to allow its manipulation. Mvreove=, the ''246 microcannula has a _. relatively complex structure, requiring the inclusion offhe-i~e;a~iovable t=oci~ to' ' ' ._ permit incision of the vessel for placeme>at.of the inii'ci~ocatuit~le; - ' ' , v ~ y ' . : . .-.
- _ . . 15 ... _. _ _~.:_. . . . . ! .. ... . ~~ . .
.. . _ _ . ~~ ~~~~ - _ .._ . _. .. . . . . .
It is a primary object of the irrventivn to provide a device ais~method of delivering a therapeutic solution i~o a beating heart~0iat iiiay~>e utitiied~iti vaiious ~~
procedures, and a more specific object of the invention to ~piovide a iniriir~ally " ~ ' ~ ' ' .
invasive device sad method of delivering angiogenesis-promoting substances from a-' - "
remote location to an area of ischemic heart tissue wi'theiut nece'ssitatuig open-client- - ' .
surgery.
It is a related object of the inveabion to provide a davici;~ snd-aiettiod of delivering angiogenesis-promoting substances to an area of di:~eased tissue with ease and e~ciency.
Another object of the invention to provide such a device that may be manigutated to contour to cardiac sad thoracic geometry.
An additional object of the invention is to provide suc~~ a device and method that facilitates i>4jection by providing stable pvaitionizrg of the :needle to easme injection intramyocardielly, as opposed to injecting into the ve~nbcicle or the pericaucdium.
AMENDED SHEET
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OCT. 26. 2001 3:18PM LEYDIG, VOLT & MAYER ~ ~' ~"Na. 2648--P. 11~

PCTIUS00/21399 3H Substihrte 56eeta A fntthar object of the invention is to provide a device and method that may ba utilized irr aroas behind or around tha heart where positiorii~~g can not be readily visually confirmed A related object is to provide such a devic a cad method that may provide non visual conf nnation of epicardial contact to facilit~~te~such appibpriate positioning of the needle tip.
Another object of the invention i~ to provide such a deuce and method with reduced trauma and reduced recovery time fig the patient: ~ ~ ~ .
A further object of the iuvenhon is to provide such a device and method that minimizes exttavasstion ofthe iajectate. -: ._ .. ~ ,- .
Yet another object of the invendon is tv provide a singio-use disposable ~ ~
~~
device that may be relatively economically manufactured such that its usage is root cost prohibitive.
AMENDED SHEET
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Y 5 ~ . . .
OCT. 26. 2001 3:19PM LEYDIG, VOIT & MAYER N0. 2648-P. 12 PCT/USOiDl21399 4 Snbsdtute Sdeets HR~.F S'f,~[~~~OF TIC I1~Y~1T_TC~
In accomplishing these and other objects of the inventicm, there is providod a flexible elvngeted needle having a stabilizing platform spaced ;from the distal tip. the needle is preferably appmximately 100-200 mm (appmly 4-8 iachas)~ long with the platform disposed obliquely, approximately 5-10 mm (approximately 0.20 to 0.80 inch) from the tip of the needle. The elongated needle i'is preferably on the --order of ZO-25 Gra (e.g., 22 Ga) and the needle tip on the ordai of 25_30 Ga (e.g., 27 Ga) with a bevel sharp tip. The platform is preferably approxirnately 5-6 mni (appmximatsly 0,20 w 0.25 inch) in diameter and is disposed obliquely reIative~to ' the needle tip. The ptoxintal end of the needle comprises-a standard liuli sized to ' ' receive the distal end of a syringe or other device for~wntamiti,g acid delivcriiag a' therapeuric sohrtion, An appropriate metering drvice may also ~be provided to -.
_ control the amount of t>xrapeutic substelnce injected at the itiiaitio:i ~si~'er' '"~.. . ....t.: :_ . , .. . :_ - - The device and method may be utilized in administrati~m of a ~therapeu4ic ' . ~. ..._ ..
=. - .. . ' : 15 solution .by injection along an outer surface ofthe heart or~alon:g a~i ititiei suiface ~Of ' ' - ~ ~ _ _ ~.
~e heart by any appropriate mdhod. In~gartzcular, as siigioga~esis-pindioti~dg ~ - ~ ' -substance, or, more speci$cally, an adenoviral vector co~iaiirg~a tiansgene ' -.
encoding a vascular endothelial geownh-factor (VEGl~; cen' be-i:itroduced~
into ~ - - - ~ .: .
myocardial tearitories in predetermined quantities at~a plut'ality of pviats~to~iafuco~ ' ~~' ..
the growth of bypass vessels which allow the bridging vPnairc~wed'oi~accliided ~ ' ' ~ ~ ' coronary vessels. The treatment also can be used to induce the: grovvlh of new' . ., ' vessels in myocardial territories poorly supplied by the: isative ~rorvnaty vasaulature.
During use, the needle is advanced into position, and ttEo needle-tip~pehe:xat~s the heart tissue. The flexibility of the elongated needle body pewits the needle to contour the path of delivery to the cardiac and thoracic gevmellry, providing the cardiologist great latitude in placement of the needle. 1hc platform, as well as its oblique positioning relative to the needle tip limits the depth o F
penetration and allows stabilization of the needle against the epicardial surfaces of the heart The solution then can be injected into the tissue by acturning the syringe. The long elongated, small diameter needle device allows for precise delivery of the inj $om a remote distance through a relatively small incision.
AMENDED SHEET y _ .___ _ ....,_ .., C...ni r,r '~~i N .I I I%

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OCT. 26. 2001 3.19PM IEY~JIG, YOIT 8r MAYER w'N0. 2648--P. 13 .

PCTIUSOOIZ1399 5 Snbititnte S6eeb The device may be utilized during op~-heart surgery, e~r advanced into the heart through any artery, including; for example, the femoral artery. The device may also be utilized in the manner disclosed in: PCT Application No.

filed March 5,1999 and designating the United States, More s)iecifically, the patient's lung may be partially collapsed by the ia~eodu~on~of~gas into the patient's thoracic cavity. This enlarges the worl~g area for injection of the therapeutic .
substance and increases access to heart tissue. The delivery of ~tho therapeutic ' . .
substaaca to the myocardium can be by way of any suitable i'vWe,~
traaspei'icardially, as well as endocardially. An elecdroae may be located on the on the~platform ~ectioa' needle, and corn~ected to as ECG, for determining wlusi the needle has paiettaxed the patient's myocatdiu~n and is properly positioned ' Peiietrati~o~ of the niyocardirmn by the needle will show as a currant injury on the F:C,G.. Thus; this anangament facilitates appropriate positioning of the acadle tip in locations bcfiiuei oz er~outid'ttie ~~ ~ .. ... . . .._ .
' heart beyond the line of sight provided by the suaface~ iu'c'~sion: ''' ' :
~ . ~ ' - ~ ..' ~ ' _ .15 ~ ~~ ~of the invention includes a device foi'~telivetiiig -a: ' ~ ' ~ ~
. _ . . ~ . . _.
.. ~o solution Erom.s~solution supply ineto cardiac t~ssue,'the device~c ~~~on8 ~" ~ , . . .. .
.. ~ a hollow needle having a pmximal and a distal end, the pi'oxim.al eiid~
being adapted .. . .
for fluid attachment to the solution supply. The needle ccitiiprises s~~elongated'body- ' ~ ~ .: ' ' and a sharpened tip disposed at the distal end of the needhand,~defiiies~ a listh df delivery from the svlurion supply to the sharp~ied tip. 'The aa~te also nncludes a '' platform spaced from the distal end. According to the~'inveaticrn; the elongated body is flexible such that it may,conform to the contour of the path of delivery of the therapeutic solution to cardiac and thoracic geometry; 'aind the ~;Platfonri acts as ~a stop ' to limit penetration of the sharpened tip into cardiac tissue and stabilizes the needle during delivery of the therapeutic solution In some of the various embodiments of the inversion, the platform is disposed obliquely relative to the: sharpened tip, the platform is spaced about 5-10 mm from the distal end, andlor'the platform is a , substantially round disc. In Borne of the various embodiments of the, invention, the elongated body is about 100-200 mm long, the needle body is a cannula of about Ga., and/or the r~ecdle body is a cannula of about 27 Ga. In arc embedirnent of the present im~tioa the device coa~rises a solution supply device and the needle AMENDED SHEET
__ .... ..",~,. r,n. ~c f-m(~t _(1f ..'.7~.71~ ('.~U 1J ' . i~'~~ 't i OCT. 26. 2001 3.19PM LEYDIG, YOIT &~MAYER ~ ~' -~b~~ ~ ' PCx'/USOOIZI399 SA ' Substitute Sheets coupled to the solution supply device. In some of the various e~abodimerns ~of the lavention, the solution supply device is a syringe, and/or the needle fuither comprises .
a hub adapted for coupling to the syringe. In some of the various eiinbodime~
of the invention, an electrode is coupled to the needle and ~adepted for connection to an ECG to provide err electrical indicative of when the sharpened tip has penetrated the cardiac tissue. In some of the various embodiments of the iavea~tion, the electrode is coupled to the platform, or the electrode is coupled to the ~sharpmed tip. ~
In somie of the various embodiments of the invention, tire device iiictiides tlhe th~peittic solution, which comprises an angiogenesis-promotsiig substaac~:. ~ .
ThGSe and other feana~es and advantages"of the inventioii will be ai6re readily appar~t upon reading the following description of a.preferred ~a~empIified ~ ~
' .
embodiment of the inve~ion and upon reference to ttie accompanying drawings: ~
. .. . .
BRIEF DESCR'~TION OF THE.DRA'GV1N~S_' _ ~. . . .
FTGURE .1 is a perspective view .of a needle consGruct~ iri ~accord'siice vvrtli' ~ ' - ' . _ . ' y.y, _...~w~- - . ~,., .:.. . . .. ...
.. ~~~gs of thc~inveiition and a dalivery syringe. ... _.. ..._ ._ . . _. . .
. _ . . ... . . .
. _ FIG. z is an enlarged fi~aerna~y view of the distal ~ eiid of the needle ~of FICA: ~ ~ ~ ' . .
1, partially broken away. :- : . . . .
1~'IG. 3 is a cross-section of the needle taken along line3-3 in FIG. ~ 2.- ~
~ ' ~~ ' . ' FIG. 4 is a cross-section of the needle taken along line 4=4 in FIG. 2. ~ ~' ~
~ ' ~ ' ~ ' FIG. 5 is a vices of the neodle of FIG, 1 extending into~tKe heart tissue: ' -' ' ' While the invention will be described in connection witJfl~certain preferred w'- ' ' embodimerns, there is no intent to limit it to those etiibodimentg, ~n~the contrary, the intent is to cover at! alternatives, modifications, aid eqtuval'.ents included within the spirit and scope of the invention as defined by the appende<t claims.
DESCRIPTION OF~~. PREF~RED ,E~IHOI
Tinning now to the drawings, there is shown in FIG. 1 a~ delivery device 6 constructed in accordance with teachings of the invention for use in delivering a therapeutic solution to the tissue of a heart, especially a beating heart The device 6 inchuies a syringe 8 or other solution supply device and a platform needle 10, The AMENDED SHEET
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The therapeutic solution my then be injected directly into the cardiac tissue in a predetermined quantity.
In the currently preferred embodiment of the invention, the solution supply device is a conventional syringe 8. The syringe 8 includes a hollow cylindrical body 16 having a distal neck-in end 18. A plunger shaft 20 with a plunger 22 mounted on the distal end thereof and a thumb button 24 mounted to the proximal end thereof is slidably disposed within the cylindrical body, the plunger extending outward from the body. During use, the operator may actuate the plunger 22 by depressing the plunger thumb button 24 to deliver the therapeutic solution.
While the solution supply device has been explained with regard to a syringe 8, it will be appreciated by those of skill in the art that the supply device can be of any appropriate design. Additionally, the supply device may include any appropriate metering device to control the amount of therapeutic substance injected at the injection site. For example, and as explained in PCT Application No.
PCT/US99/03731 filed March 5, 1999, the syringe 8 may include a shaft having screw threads or include a ratchet mechanism which permits the plunger button to advance within the cylindrical body only a predetermined distance to permit only a predetermined amount of therapeutic solution to be administered at a given injection site. Alternately, the administration of a controlled amount of the therapeutic solution may be facilitated by computer controlled device.
In accordance with the invention, the inventive platformed needle 10 includes an elongated flexible body or cannula 30, as shown in FIGS. 1 and 2, having an elongated bore 32 extending therethrough. In the preferred embodiment of the invention, the needle body 30 is on the order of 100-200 mm (4 to 8 inches) long.
According to an important feature of the invention, the needle body 30 desirably is be sufficiently flexible to permit the needle body 30 to contour to cardiac and thoracic geometry. It will be appreciated by those of skill in the art that this flexibility of the needle body 30 provides the cardiologist significant latitude in the maneuvering and proper placement of the needle within the body while minimizing the invasiveness of the procedure. It has been determined that a 22 Ga (or 22 gauge) needle provides a sufficiently rigid, yet adequately flexible structure which may be readily utilized by the cardiologist during a procedure.
To facilitate penetration of the needle 10 into the cardiac tissue, a preferably smaller diameter needle tip 40 is provided at the distal end 12 of the needle body 30.
It has been determined that a 27 Ga (or 27 gauge) cannula is particularly appropriate.
It will be appreciated by those of skill in the art that this small gauge needle tip 40 minimizes extravasation of inj ectate. In the illustrated embodiment, the needle tip 40 includes a bevel sharp tip 42. A bore 43 extending through the needle tip 42 is in communication with the elongated bore 32 of the needle body 30 and opens at the bevel tip 42. While a bevel tip is illustrated, it will be appreciated that an alternate tip geometry or structure may provided.
According to another important feature of the invention, in order to facilitate proper transfer of the therapeutic solution, penetration of the needle tip 40 into the tissue is structurally limited. To limit the penetration, the needle 10 is provided with a platform 44 which is spaced from the end of needle tip 42 at the distal end 12 of the needle 10. In this way, during use, the depth to which the needle tip 40 may penetrate the tissue is governed by the proximity of the platform to the distal tip 45 of the needle 10. It is presently anticipated that the distal surface of the platform 44 will be disposed on the order of 5-10 mm from the distal tip 45, although alternate spacing may be dictated by factors such as the particular therapeutic solution utilized, 1 S or the physical characteristics of the tissue upon which the procedure is to be performed.
In the preferred design, the platform 44 is in the form of a substantially round, flat disc, minimizing the likelihood of any irritation to tissue due to sharp corners.
Preferably, the platform is on the order of 4 to 6 mm in diameter. It has been determined that a 0.5 mm (0.020 inch) thick, 3.5 mm (0.125) inch diameter 304 stainless steel disc is appropriate.
Although the needle tip 40 and the platform 44 may be disposed at a right angle, to further stabilize the needle 10 during delivery of the therapeutic solution, the platform 44 is preferably disposed obliquely the needle tip 40, as shown in FIGS.
1, 2 and 5. In this way, the opportunity for further twisting or rotation of the needle 10 once properly positioned is minimized. Preferably, the platform 44 disposed at an angle on the order of a few degrees from the needle tip 40, although an alternate angle may be provided.
In order to couple the needle 10 to the solution supply device, an appropriate coupling 50 is provided at the proximal 14 end of the body 30. In the currently preferred embodiment, the coupling is in the form of a metal hub SO having a large bore 52 extending therethrough for receiving the distal neck-in end 18 of the syringe.
The metal hub 50 further includes a smaller size bore, which communicates with the large bore 52 and the elongated bore 32 of the needle body 30 such that fluid communication is established between the hollow cylindrical body 16 of the syringe 8 and the elongated bore 32 of the needle body 30. While in the currently preferred embodiment, the hub is a "Luer Lock," it will be appreciated that an alternate structure may be utilized, or the needle body 30 may be directly coupled to the syringe 8 or other supply device.
During assembly of the needle 10, the needle body 30, the needle tip 40 and the platform 44 may be laser welded at one common junction. The smaller diameter needle tip 40 may be slip fit into the larger diameter needle body 30, and the platform 44 fit to the needle tip 40. Similarly, the hub 50 may be laser welded to the proximal end of 14 of the needle body 30.
According to another feature of the invention, the cardiologist may utilize the needle 10 in positions that are typically beyond the line of sight provided by way of a surface incision. An electrode 60 similar to that disclosed in PCT Application No.
PCT/US99/03731, filed March 5, 1999, may be provided on the platform 44 (as illustrated) or at the tip of the needle 42, as shown in FIG. 4, and insulated therefrom.
Alternately, the needle itself may serve as an electrode if the needle tip 40 or the platform 44 are made from a conductive material. Electrical connection of this electrode 60 to an electrocardiograph ("ECG") (not shown) may be made by running an electrical conductor along the needle 10 to the ECG located outside the patient's body. Standard surface ECG leads are likewise applied to the patient. When the electrode 60 enters the patient's myocardium 62 (see FIG. 5), the event shows as a current injury. In this way, the cardiologist may ensure that the desired positioning and contact is made with the myocardium prior to actuation of the solution supply device 8.
Consequently, the invention provides a device for the delivery of a therapeutic solution, in particular, an angiogenesis-promoting substance (particularly an adenoviral vector containing a transgene encoding a vascular endothelial growth factor (VEGF)) into a heart, especially a beating heart. The device includes an elongated needle 10 having a stop, or platform 44 spaced from the distal needle tip 42. In use, the cardiologist accesses the thoracic cavity and heart tissue by any appropriate method. The needle tip 40 is then maneuvered into a desired position for delivery of the solution. Significantly, the elongated needle body 30 is flexible enough to maneuver around thoracic and cardiac geometry, yet sufficiently rigid to facilitate such maneuvering. When the needle tip 40 is a desired position, the needle 10 is advanced to penetrate the cardiac tissue. In doing so, the platform 44 limits the depth to which the needle tip 40 may penetrate the tissue and stabilizes the needle.
The solution is then delivered to the site by actuation of the supply device, preferably, in this case, a syringe.

In the minimally invasive procedure, the elongated, small diameter needle device allow delivery of the solution "at a distance" through small incisions, possibly without the use of endotracheal intubation. Moreover, the simple design of the needle 10 may be economically manufactured, facilitating disposability. It is currently anticipated that approximately 10-30 needles will be utilized per patient in a typical administrative procedure of a therapeutic solution.

Claims

WHAT IS CLAIMED IS:

1. A device 6 for delivering a therapeutic solution from a solution supply into cardiac tissue 62, the device comprising a hollow needle 10 having a proximal and a distal end 14, 12, said proximal end 14 being adapted for fluid attachment to said solution supply 8, said needle 10 comprising an elongated body 30 and a sharpened tip 40 disposed at said distal end 12 defining a path of delivery from the solution supply to the sharpened tip 40, and a platform 44 spaced from the distal end 12, characterized in that the elongated body 30 is flexible such that it ma conform the contour of the path of delivery of the therapeutic solution to cardiac and thoracic geometry, and said platform 44 acting as a stop to limit penetration of the sharpened tip 40 into cardiac tissue 62 and whereby the platform 44 stabilizes the needle 10 during delivery of the therapeutic solution.

2. The device 6 of claim 1 wherein the platform 44 is disposed obliquely relative to the sharpened tip 40.

3. The device 6 of claim 1 wherein the platform 44 is spaced about 5-10 mm from the distal end 12.

4. The device 6 of claim 1 wherein the platform 44 is a substantially round disc.

5. The device 6 of either of claims 1 or 3 wherein the elongated body is about 100-200 mm long.

6. The device 6 of any of claims 1, 3, or 5 wherein the needle body is a cannula of about 22 Ga.

7. The device 6 of any of claims 1, 3 or 5 wherein the needle body is a cannula of about 27 Ga.

8. The device 6 of claim 1 comprising a solution supply device 8, said needle 10 being coupled to said solution supply device 8.

9. The device 6 of claim 8 wherein the solution supply device 8 is a syringe 8.

10. The device 6 of claim 9 wherein the needle 10 further comprises a hub 50 adapted for coupling to the syringe 8.

11. The device 6 of claim 1 further comprising an electrode coupled to the needle 10 and adapted for connection to an ECG to provide an electrical indication of when said sharpened tip 40 has penetrated the cardiac tissue 62.

12. The device 6 of claim 11 wherein the electrode is coupled to the platform-44.

13. The device 6 of claim 71 wherein the electrode is coupled to the sharpened tip 10.

14. The device 6 of claim 1 wherein the device 6 includes the therapeutic solution, said therapeutic solution comprising an angiogenesis-promoting substance.

15. A method of delivering a therapeutic solution into cardiac tissue, the method comprising the steps of providing a hollow needle 10 having a proximal end and a distal end 12 in fluid attachment with a solution supply 8, providing access to the thoracic cavity, advancing an elongated flexible body 30 of the needle 10 into the thoracic cavity, positioning a sharpened tip 40 disposed at said distal end 12 of the needle 10 adjacent the target cardiac tissue 62, advancing the sharpened tip 40 into the tissue 62 until a platform 44 of the needle 10 which is spaced from the distal tip 42 of the needle 10 comes into contact with the cardiac tissue 62 to stabilize the needle 10 relative to the tissue 62, delivering the therapeutic solution through the needle 10 to the tissue 62, removing the needle 10.

16. The method of claim 15 wherein the solution comprises an angiogenesis-promoting substance.

17. The method of claim 25 wherein the platform-44 is obliquely disposed relative to the sharpened tip 40, and the method further comprises the step of advancing the needle tip 40 into the tissue 62 at an angle to the surface of the target cardiac tissue 62.

18. The method of claim 25 further comprises the step of flexing the needle body 30 to conform to thoracic and/or cardiac geometry.

19. The method of claim 25 further comprising the step of inserting the needle body 30 into the patient through a port inserted into an incision in the patient's body.

20. The method of claim 25 further comprises the step of at least partially collapsing the patient's lung.

21. The method of claim 25 further comprising the step of advancing the needle 10 into the heart 22 through a ventricle.

22. The method of claim 25 further comprising the step of advancing the needle 10 toward the heart 62 through the femoral artery.

23. The method of claim 25 further comprising the step of providing as electrical signal from the distal end 12 of the ncedlc 10 to an ECG.