WO2000013734A2 - Method for re-perfusion of oxygenated blood - Google Patents

Method for re-perfusion of oxygenated blood Download PDF

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Publication number
WO2000013734A2
WO2000013734A2 PCT/US1999/020100 US9920100W WO0013734A2 WO 2000013734 A2 WO2000013734 A2 WO 2000013734A2 US 9920100 W US9920100 W US 9920100W WO 0013734 A2 WO0013734 A2 WO 0013734A2
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WO
WIPO (PCT)
Prior art keywords
microcatheter
blood
sub
main body
re
Prior art date
Application number
PCT/US1999/020100
Other languages
French (fr)
Other versions
WO2000013734A3 (en
Inventor
Jeffrey A. Lee
Original Assignee
Neurovasx, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US9947498P priority Critical
Priority to US60/099,474 priority
Priority to US12684199P priority
Priority to US60/126,841 priority
Priority to US09/374,402 priority
Priority to US37440299A priority
Application filed by Neurovasx, Inc. filed Critical Neurovasx, Inc.
Publication of WO2000013734A2 publication Critical patent/WO2000013734A2/en
Publication of WO2000013734A3 publication Critical patent/WO2000013734A3/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0067Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0068Static characteristics of the catheter tip, e.g. shape, atraumatic tip, curved tip or tip structure
    • A61M25/007Side holes, e.g. their profiles or arrangements; Provisions to keep side holes unblocked
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22038Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with a guide wire
    • A61B2017/22042Details of the tip of the guide wire
    • A61B2017/22044Details of the tip of the guide wire with a pointed tip
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22082Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
    • A61B2017/22084Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance stone- or thrombus-dissolving
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/01Introducing, guiding, advancing, emplacing or holding catheters
    • A61M25/09Guide wires

Abstract

The present invention includes a re-perfusion circuit that comprises an oxygenator and a heat exchanger for adjusting temperature of blood or a blood substitute. Temperature adjustment is made with a temperature sensor and a controller.

Description

METHOD FOR RE-PERFUSION OF OXYGENATED BLOOD

Field of the Invention

The present invention relates to a method for providing neuro-protection during the treatment of an acute stroke, or distal perfusion to a blockage within an artery.

Background of the Invention

In an acute stroke, a blockage is formed within a vessel by a thrombus or a clot. In treating acute stroke, an objective is to remove the blockage caused by the thrombus as quickly as possible. In numerous clinical studies, it has been shown that if the blockage can be removed within the first six hours after a stroke, the chance for patient recovery with little or no permanent neurologic deficit is significantly improved. Many practitioners believe that a window of opportunity is limited to the first three hours following blockage.

The thrombus is comprised of various blood components that can be dissolved or lysed with drugs. In conventional stroke therapy, these lytic drugs are given by systemic intravenous (IV) administration. Consequently, a drug is infused throughout the entire circulatory system. A more aggressive treatment is to deliver the lytic drugs directly to the thrombus utilizing a catheter. The catheter is positioned adjacent to the thrombus and the drug is infused directly onto the thrombus. The benefit is that the drug, in a much higher concentration, reaches the thrombus for improved effectiveness. One type of drug delivery system utilizes a microcatheter. Microcatheters that are intended for insertion into the vasculature of the brain rely upon the flexibility of polymeric material from which the microcatheters are fabricated for the characteristics of trackability and pushability. Trackability as used herein refers to a characteristic of a microcatheter to "track over" a guidewire to an intended treatment location. Microcatheters must exhibit superior trackability to traverse the tortuous anatomy in the brain.

Pushability as defined herein refers to a characteristic of a microcatheter to transmit an axial pushing force from a proximal end of the catheter, which is the operator end, to a distal end of the microcatheter, the end of the catheter in the patient. Physicians expect that they can push the microcatheter effortlessly within the anatomy of a living being. Microcatheters are typically designed to enhance these characteristics with a particular polymer selection for the catheter body or a catheter shaft. Polymers may be blended or coextruded to provide a proper mix of flexibility and rigidity. A microcatheter shaft may vary in flexibility over its length, being more flexible and less rigid at a distal end of the microcatheter and less flexible and more rigid at the proximal end of the microcatheter. This result may also be accomplished by varying the microcatheter shaft diameter and wall thickness.

An Engelson patent, U.S. No. 4,739,768, issuing April 26, 1988, and Re-examination Certificate No. B14739768, issuing June 16, 1993, describes a catheter used in conjunction with a guidewire for treating a target tissue. The catheter includes an elongate tubular member with a proximal end and a distal end, the tubular member defining an inner lumen. The tubular member has a stiff proximal segment making up about 70% to 95% of the total length of the tubular member as well as a flexible distal segment that makes up the remaining 5% to 30%) of the length of the tubular member. The proximal segment defines inner and outer coaxial tubes.

A Samson et al. patent, U.S. No. 5,462,523, issuing October 31, 1995, describes a catheter for delivering drugs to regions of a human body accessible through systems of passage ways, such as blood vessels. The catheter includes a guidewire and a tubular elongate body. The elongate body includes a distal segment that is flexible thereby rendering the catheter trackable along the guidewire. The main body further includes a profusion tip with an opening permitting a perfusion of drugs at a particular site. The tip is made up of an inner stiffener which is somewhat porous and an outer profuser layer which controls fluid flow to a relatively low rate. A Schweich, Jr. et al. patent, U.S. No. 5,782,797, issuing July 21, 1998, describes a method for treating an occlusion of human vasculature as in stroke. The method requires providing a device with two distinct sets of infusion lumens. The device is advanced through vasculature so that one lumen is distal to a thrombus and one lumen is proximal to the thrombus. A neuroprotective drug is infused through an opening distal to the thrombus and a thrombolytic drug is infused through an opening proximal to the thrombus. The Schweich Jr. patent describes a device that has a fixed distance between infusion holes at each end of the inner and outer catheter. Consequently, this device has limited use. For instance, the Schweich device cannot be adjusted or aligned to accommodate lesion length.

Summary of the Invention

One embodiment of the present invention comprises a method for providing oxygenated blood or a blood substitute to brain tissue and brain blood vessels deprived of oxygen as a result of a thrombus formation or embolic stroke. The method includes providing a sub-microcatheter. The sub-microcatheter includes a unitary, flexible main body defining a lumen and having a distal end and a proximal end. The main body defines a plurality of ports positioned proximally to the distal end. The sub-microcatheter also includes an infusion hub that is positioned proximally to the plurality of ports and the distal end. The method includes positioning the sub-microcatheter so that the plurality of ports are distal with respect to the thrombus; that is, within an oxygen deprived region. The method additionally includes perfusing oxygenated blood or an oxygenated blood substitute through the ports into the brain tissue and brain blood vessels oxygen deprived as a result of thrombus formation. Another embodiment of the present invention comprises a sub-microcatheter. The sub-microcatheter comprises a unitary, flexible main body that defines a lumen. The lumen has a distal end and a proximal end. The main body defines a plurality of ports that are positioned proximally to the distal end. The sub-microcatheter also includes an infusion hub positioned proximally to the plurality of ports and to the distal end.

One other embodiment includes a sub-microcatheter-microcatheter combination. The sub-microcatheter comprises a unitary, flexible main body defining a lumen and having a distal end and a proximal end. The main body defines a plurality of ports positioned proximally to the distal end. The sub-microcatheter also includes an infusion hub positioned proximally to the plurality of ports. The combination also includes a microcatheter that comprises a main body with an annular wall defining a plurality of ports. The microcatheter main body terminates to form an annulus about the main body of the sub-microcatheter so that anti-thrombic drugs are administered through the annulus and out the ports.

The present invention further includes a re-perfusion circuit. The re-perfusion circuit includes a source of blood or a blood substitute and a sub-microcatheter with a side hub for receipt of the blood or blood substitute. The blood or blood substitute is transported to the sub-microcatheter by a conduit.

In one embodiment, the re-perfusion circuit further includes a heat exchanger and a temperature sensor for adjusting the temperature of the blood or blood substitute. The temperature sensor communicates with a controller which regulates flow of a heat exchange media in the heat exchanger to adjust temperature in a feedforward control scheme, a feedback scheme or a feedforward-feedback scheme. Brief Description of the Drawings

Figure 1 is a side view of one embodiment of the sub-microcatheter of the present invention.

Figure 2 is a side view of a mandril that is positionable within the sub-microcatheter. Figure 3 is a side view of one embodiment of the sub-microcatheter of the present invention.

Figure 3a is a perspective view of one embodiment of the sub-microcatheter positioned within the microcatheter of the present invention.

Figure 4 is a side view of a position of the sub-microcatheter with respect to a thrombus for re-perfusion.

Figure 4a is an annular cross-sectional view of one other embodiment of the sub- microcatheter positioned within the microcatheter.

Figure 5 is a side view of a position of the sub-microcatheter and a microcatheter with holes with respect to a thrombus for re-perfusion. Figure 6 is a schematic view of one embodiment of an extracorporeal circuit of the present invention.

Figure 7 is a schematic view of one other embodiment of a re-perfusion circuit of the present invention with a pump and an oxygenator cell.

Figure 8 is a schematic view of another embodiment of a re-perfusion circuit of the present invention with a syringe.

Figure 9 is a schematic view of one other embodiment of a re-perfusion circuit of the present invention with a pump and a cooler located before the oxygenator.

Figure 10 is a schematic view of one other embodiment of a re-perfusion circuit of the present invention with a pump and two coolers positioned in series with respect to the pump and the oxygenator.

Figure 11 is a schematic view of another embodiment of a re-perfusion circuit of the present invention with a pump and a cooler located after the oxygenator.

Detailed Description of Preferred Embodiments

The method of the present invention, for delivering oxygen saturated blood or blood substitute to an ischemic territory of the brain of a living being, which is downstream from a thrombus causing a stroke, comprises providing a sub-microcatheter, such as is illustrated at 200 in Fig. 1, with a distal end 112 defining a plurality of ports 412a, b, c, d, e and f. The sub-microcatheter 200 is advanced to the thrombus 8, so that the distal end 112 penetrates and passes through the thrombus 8 as is shown in Fig. 3, and, in one embodiment, infuses oxygenated blood from a femoral circulation of the living being 11 through a closed loop extracorporeal circuit such as is illustrated at 100 in Fig. 6, into a hub 310 and out through the ports 412a, b and c, into ischemic territory of the brain which is downstream from the thrombus 8.

In one embodiment of a microcatheter-sub-microcatheter combination, illustrated at 300 in Fig. 3, a microcatheter 210 defines ports 220 a, b, c, d, e, and f that permit an infusion of thrombolytic drugs into the thrombus 8. The drug infusion may be performed concurrently with the perfusion of oxygenated blood through the sub-microcatheter 200 or may be performed separately. Each of the drug infusion and oxygenated blood perfusion may be performed intermittently and independently of each other.

The present invention also includes the sub-microcatheter 200 that is a component of the extracorporeal circuit such as is illustrated at 100 in Figure 6 or 500 in Figure 7 or 600 in Figure 8. The sub-microcatheter 200 comprises the hub 310 for receipt of re-perfused, oxygenated blood or a blood substitute as shown schematically in Fig. 7. The blood may be oxygenated by an oxygenator, illustrated at 320 in Figure 7. The blood or blood substitute may be delivered to the extracorporeal circuit by a syringe as is illustrated at 330 in Figure 8. The method of the present invention not only promotes rapid thrombolysis but minimizes damage to ischemic territory within the brain by infusing oxygenated blood into the ischemic territory. The dual functionality of the microcatheter-sub-microcatheter combination 300 renders the combination device a powerful tool in minimizing brain damage due to stroke. The dual functionality permits a medical practitioner to rapidly and simultaneously, address two critical problems of stroke. The first problem concerns how to eliminate the thrombus. This problem is addressed by local anti-thrombolytic drug delivery to the thrombus. The second problem concerns how to minimize damage to blood starved tissue in the ischemic region. This problem is addressed by infusing oxygenated blood into the ischemic territory. One other benefit of the dual functionality is that, once the microcatheter-sub- microcatheter combination 300 is positioned optimally with respect to a thrombus, the functions of disrupting the thrombus and preserving oxygen-deprived tissue are de-coupled from each other. Thus, the practitioner has an ability to only feed oxygenated blood or blood substitute in a spectrum of quantities, flowrates and oxygen concentration and an ability to only feed thrombolytic drugs in a spectrum of flowrates and quantities.

While oxygenated blood is described, it is understood that other oxygen-imparting fluids, such as blood substitutes may be imparted by the microcatheter-sub-microcatheter combination 300 of the present invention. In one embodiment, a fluorocarbon blood substitute comprising lysophosphatidyl compounds in non-toxic concentrations is employed. One fluorocarbon blood substitute is described in U.S. Pat. No. 5,374,624, issuing December 20, 1994, and is hereinafter incorporated by reference. Other blood substitutes include materials that incorporate nitric oxide delivery, super-oxygenated saline, neuroprotectants such as NMD A antagonists, anti-TNF, and so forth, anti-oxidants and free radical spin traps, modified or synthetic constructs of hemoglobins, ions, free and bound such as magnesium, genes and gene fragments, nitric oxide donors and/or inhibitors, calcium and/or iron chelating compounds, growth factors such as bFGf, and so on, steroids and/or other similar tissue edema reductants and/or combinations of any of these blood substitute materials. Compatible blood from another living being may also be utilized or, alternatively, hemodilution of the patient's own blood may be administered.

It is also contemplated that the device of the present invention is usable to infuse a biodegradable drug carrier, such as a viscous or gelling polymer like a hydrogel, that coats the interior of a vessel wall to permit greater exposure and penetration of any of the blood products and blood substitutes described herein. The infusion of the gelling polymer is believed to improve efficacy of the blood products and blood substitutes. The infusion device of the present invention is also usable in conjunction with devices that can fabricate an in situ laminar boundary layer at or near the wall of a blood vessel.

The present invention additionally includes the extracorporeal circuit such as is shown at 100 that comprises the femoral/iliac access sheath 309 with a side arm 312 for infusion or aspiration of fluids from the iliac/femoral artery of the living being 11. Fluid such as oxygenated blood is then passed through a pump 306 or injection device through a line 304 to the side hole infusion hub 310 of the sub-microcatheter 200 as is illustrated in Fig. 6.

The sub-microcatheter component of the present invention, illustrated generally at 200 in Fig. 1, includes a flexible main body 12 defining a lumen 33 with a distal end 112 and a plurality of ports 412 a, b, c, d, e and f positioned proximally to the distal end 112, the main body 12 further terminating in a proximal end 20 opposing the distal end 112. The sub- microcatheter 200 encloses a mandril 22 within the lumen 33. The mandril 22 shown in Fig. 2 includes a shaft 24 and a taper section 26 extending distally from the shaft 24.

The sub-microcatheter main body 12 further includes marker bands 29 a and b, positioned adjacent each of the ports 412a-f. The marker bands 29a and b enable an individual, such as a physician, positioning the sub-microcatheter 200 to precisely position the main body 12 through a thrombus 8 such as is shown in Figs. 3, 4, and 5.

The position of the mandril 22 within the lumen 33 of the flexible main body 12 of the sub-microcatheter 200 permits the sub-microcatheter main body 12 to be constructed utilizing a single extrusion of a polymer. In one embodiment, the polymer is a high density polyethylene. In other embodiments, the sub-microcatheter main body 12 is made of a material such as polypropylene, ethylene vinyl acetate (EVA), nylon or polyimide. With these materials of construction, the main body 12 has a uniform flexibility and rigidity throughout its entire length. In a preferred embodiment, the main body 12 is extruded so that the diameter and wall thickness as well as the polymeric material of construction render the main body 12 highly flexible with very little rigidity.

The mandril 22 which is preferably made of a metallic material such as Nitinol, super elastic Nitinol, stainless steel, or a cobalt chromium alloy such as Elgiloy manufactured by Elgiloy Corp. of Elgin, Illinois, imparts a reversible and variable rigidity and flexibility to the main body 12 of the sub-microcatheter 200. One typical composition of Elgiloy includes 40%) cobalt, 20%> chromium, 15%> nickel, 7% molybdenum, 2% manganese, 0.15% carbon, 0.04%) beryllium with the remaining weight percent being iron. Further information on Elgiloy is described in U. S. Patent No. 2,524,661, which is incorporated herein by reference. The mandril 22 also imparts to the main body 12 the variable flexibility and rigidity required to advance the sub-microcatheter 200 through a microcatheter and a blood vessel. In particular, the flexibility and rigidity optimizes steerability and pushability of the sub- microcatheter 200 through an anatomy of a living being.

Once the sub-microcatheter 200 is in a proper treatment site position, through a thrombus 8 such as is illustrated in Figs. 3, 4, and 5, the mandril 22 is removed, leaving the highly flexible sub-microcatheter main body positioned within an artery or vein. Once positioned within the artery or vein, the sub-microcatheter 200 is positioned so that the distal end 112 is passed through a thrombus. Oxygenated blood or a blood substitute is delivered through the ports 412a-f. The oxygenated blood or blood substitute acts to provide oxygen to blood vessels and brain tissue downstream of the thrombus, thereby reducing damage to the tissue.

The sub-microcatheter component 200 of the present invention fits within a microcatheter 50 as shown in Figure 4 or a microcatheter 210 as is shown in Fig. 3 or a microcatheter 360 as is shown in Fig. 5. The microcatheters 50, 210, and 360, each provides to a physician a guide catheter that facilitates advancement and placement of the sub- microcatheter 200.

The microcatheter 210, shown in Fig. 3, comprises a main body 250 with an end hole 221 and one or more ports 220a-f for anti-thrombic drug delivery. The microcatheter 360 defines one or more sideholes 340a, 340b and 340c for anti-thrombic drug delivery.

The sub-microcatheter 200 may be positioned through the hole 221 and contacts an annular wall 223 of the microcatheter 210 as shown in cross-section in Fig. 3 a. The annular wall 223 is made of a material that seals the microcatheter 210 about the sub-microcatheter 200 as is shown in Fig. 3 a. The microcatheter embodiment 210 differs from the microcatheters 50 and 360 by the presence of the annular seal.

To position the microcatheter-sub-microcatheter unit 300, one of the microcatheters 50, 210 or 360, is advanced along a guidewire in a conventional manner. For instance, a cannula, such as is shown schematically at 309 in Fig. 6, is introduced into a femoral artery of an individual with a blood clot in a blood vessel within or proximal to the brain. A guide catheter, shown schematically at 311 in Fig. 6, is inserted into the femoral artery through a lumen defined by the canula 309. The guide catheter 311 is advanced using fluoroscopic guidance, to a point in the proximal extracranial circulation of the living being. The microcatheter is advanced over a guidewire which is not shown until the microcatheter is adjacent to the blood clot. The sub-microcatheter 200 is then inserted through the clot. The sub-microcatheter 200 does not require a separate guidewire for positioning.

Advancement of the sub-microcatheter 200 and the mandril 22 is accomplished by moving the metallic mandril 22 to the distal end 112 of the sub-microcatheter 200. The sub- microcatheter' s distal tip 112 is sealed shut so that the mandril 22 can transmit push forces through the sub-microcatheter 200 which is advanced to a treatment site, such as the blood clot, as a single unit through the microcatheter 50. In one embodiment, the mandrel includes a blunt tip which is radiopaque for fluoroscopic guidance.

In one embodiment, the mandril 22 is coated with a lubricious agent such as a silicone oil, a hydrogel or other hydrophilic coating in order to render the mandril 22 easier to manipulate. Similarly, the sub-microcatheter 200 is also, in one embodiment, coated with a lubricious coating such as silicone oil, hydrogel, or other hydrophilic coating. The coating preferably covers a distal section of about 20 centimeters of the sub-microcatheter where the catheter is reduced in diameter to a range of approximately 0.014 inches to 0.016 inches. The catheter diameter may be somewhat larger.

Microcatheters tend not to be very steerable. As a consequence, torque transmission from a proximal end to a distal end of the microcatheter is either severely limited or nonexistent. This lack of steerability and torqueability limits the microcatheter' s ability to access abrupt turns or branch vessels. Current microcatheters require the assistance of a guidewire to steer the microcatheter into position. The sub-microcatheter 200 of the present invention overcomes this significant problem by placement of the mandril 22 within the sub- microcatheter thereby rendering the sub-microcatheter steerable and pushable.

It is contemplated that the sub-microcatheter may be steered by use of a steerable guidewire in the sub-microcatheter lumen in place of the mandrel. The steerable guidewire has a diameter of about 0.010 inches to 0.012 inches. The distal 5 centimeters of a sub- microcatheter embodiment with a mandrel in the lumen has a flexibility that is equivalent to a 0.014 inch steerable guidewire.

The sub-microcatheter 200 of the present invention is inserted after one of the microcatheters, 50, 210 or 360 accesses the artery and is positioned proximal to the thrombus. The sub-microcatheter 200 is supported by the microcatheter while the thrombus is being penetrated. After the sub-microcatheter 200 is safely positioned beyond the thrombus, the mandril 22 is removed and infusion of blood or blood substitute is begun utilizing one of the circuits that are shown in Figs. 6, 7 or 8. As an adjunct to this treatment, lytic drugs may also be infused through the conventional microcatheter to provide one or more lytic drugs at the thrombus.

The mandril 22 extends beyond the proximal end of the sub-microcatheter 200 so that the mandril 22 is gripable by a physician. The mandrel has a maximum diameter that is preferably about 0.012 inches, which is tapered over a distal length of 20 centimeters to 0.004 inches in diameter. One mandrel embodiment illustrated in Fig. 2 terminates in a blunt tip. For this embodiment, the blunt tip diameter is greater than the adjacent 0.004 inch tapered section and is preferably about 0.008 inches in diameter. Additionally, a Luer tapered fitting of the sub-microcatheter 200 includes a pair of finger grip wings 25a and 25b as shown in Fig. 1 that enable a user, such as a physician to adequately grip the Luer tapered fitting and lock accessory devices such as hemostatic valves and infusion devices to the Luer tapered fitting. The lumen of the tapered fitting facilitates an effortless loading of the mandril 22 in the sub-microcatheter main body lumen. The mandril 22 is loaded and positioned within the lumen in a manner that permits the physician to rotate and torque the mandril 22 and to steer the distal tip 112 of the sub-microcatheter 200 without hindering pushability or steerability. Between the sub-microcatheter and the mandrel is an annular space that is preferably about 0.002 inches to aid in pushability or steerability by the mandrel.

The sub-microcatheter tip is steerable by rotating the mandrel within the catheter lumen. In particular, the mandrel is locked to the sub-microcatheter at the proximal end with a Touhy-Borst fitting. The catheter assembly is rotated as a unit. The tip of the catheter is deflected for steering by axially pushing on the mandrel against the closed distal tip.

The holes 412a-f defined by the main body 12 are in one embodiment equally spaced around the main body 12 about 90° apart. The infusion holes 412 a-f are about 0.005 inches in diameter. The holes are smaller than the blunt tip of the mandrel in order to prevent the mandrel from exiting the sub-microcatheter through the infusion hole. In one embodiment, marker bands, 29a and 29b, are embedded in the catheter lumen adjacent to the infusion holes 412 a-f. The sub-microcatheter 200 is shaped so that the main body portion defining the holes 412a-f may be inserted directly into and through a thrombus 8 as shown in Figs. 3, 4 and 5. Once the main body 12 is inserted through the thrombus 8, oxygenated blood or a blood substitute may be infused through the holes 412 a-f. Preferably, the sub-microcatheter does not include a hole at the end of the sub-microcatheter. Rather, the hub 310 is positioned proximal to the distal end 112.

In one embodiment, the main body 12 of the sub-microcatheter is made of a material such as high density polyethylene. The main body 12 has a wall thickness of about 0.002 inches. The sub-microcatheter 200 has a diameter, preferably, of about 0.018 inches or smaller. The lumen diameter defined by the main body is about 0.014 inches, minimum. It is understood, however, that the main body may be sized to have other dimensions. It is important that the diameter allows the sub-microcatheter 200 to easily navigate within a conventional microcatheter through a blood vessel. In an embodiment of the sub-microcatheter 200 illustrated in Fig. 6, the side hole infusion hub 310 is linked with a line 304 to a pump 306 or injection device. The pump 306 may be a roller pump or a peristaltic pump. The pump 306 or injection device receives oxygenated blood from the patient through an iliac or femoral artery access 308. In one embodiment, oxygenated blood is transferred from the iliac or femoral artery access 308, re-perfused through the side hole infusion hub 310 of catheter 200 perfusion holes 412 a-f at a rate compatible with flow capacity of the blood vessel into which the perfused blood or blood substitute is infused. The access sheath 308 includes a side arm 312 for infusion or aspiration of fluids. In one other embodiment, illustrated in Figure 8, oxygenated blood or a blood substitute is transferred from a syringe 330 to the sub- microcatheter.

Once the sub-microcatheter 200 as shown in Fig. 7 is positioned so that ports 412a-f extend through the thrombus, the re-perfused oxygenated blood is conveyed from femoral circulation of the patient to the femoral/iliac access sheath. In particular, once the sub- microcatheter is positioned, oxygenated blood is connected to an inlet port 301 of oxygenation device 320. An outlet port 303 of the oxygenation device 320 is connected to the sub-microcatheter so that oxygenated perfusion blood exiting the oxygenation device 320 will pass through the sub-microcatheter 200 through the side hole infusion hub 310 and out through the ports 412a-f into the ischemic territory of the living being. The pump 306 or other fluid propulsion device may be used to cause blood to flow from the access sheath to the ischemic territory.

The oxygenation device also includes a gas inlet 307 for receipt of oxygenated gas from a gas supply source and a gas outlet 308 for release of carbon dioxide. The oxygenation device is sized to accommodate a flow of blood to the ischemic territory that is not detrimental to the living being.

In one embodiment, illustrated at 600 in Fig. 9, the re-perfusion circuit also includes a heat exchanger 602 positioned proximal to an oxygenator 604. The heat exchanger 602 includes, in one embodiment, a shell 603 for transport of the blood or blood substitute and an array of tubes 605 enclosed within the shell 603 for a heat exchange medium such as chilled water or a cooled saline solution. In another embodiment, the shell 603 transports the heat exchange medium and the array of tubes 605 transports the blood.

A temperature sensor 606 is also positioned within the re-perfusion circuit 600. In the embodiment illustrated in Fig. 9, the temperature sensor 606 is positioned after the heat exchanger 602. Temperature data obtained by the temperature sensor 606 is used by a controller 610 to adjust coolant flowrate in the heat exchanger 602. A feedback control scheme is shown in Fig 9. It is also contemplated that a temperature sensor 608 may be positioned before the heat exchanger 602. The sensor 608 may be used in a feed forward control scheme for blood or blood substitute temperature control. The control scheme shown in Fig. 9 may be a feed forward, feedback or feed forward-feedback. In one embodiment, the blood or blood substitute is cooled to a temperature of about 40 degrees Fahrenheit.

In another embodiment, illustrated at 700 in Fig. 10, heat exchangers 702 and 704 are positioned at each of the inlet and the outlet of an oxygenator 706. With this embodiment, a temperature sensor 708 is positioned after or downstream of heat exchanger 704. The temperature readings from the temperature sensor 708 may be used in a feedback control scheme.

In one other embodiment, a temperature sensor 710 is positioned upstream of the heat exchanger 702. Temperature readings from this temperature sensor may be used in a feed forward control scheme or in a feed forward-feedback control scheme. With these control schemes, the heat exchangers may be interrelated in a series configuration or in a parallel configuration.

Another embodiment, illustrated generally at 800 in Fig. 11 , includes a pump 802 connected in series to a heat exchanger 804 and oxygenator 806.

Presented below are specific examples of the device of the present invention. The examples are presented to describe particular embodiments and are not intended to limit the scope of the present invention.

Example 1

One embodiment of the extracorporeal circuit of the present invention is illustrated at 100 in Fig. 6. With this embodiment, blood is removed from a living being 11 through the access sheath 309. The access sheath includes the side arm 312 that directs blood through a conduit to the pump 306 and then to the hub 310 of the sub-microcatheter 200. From the sub- microcatheter 200, the blood flows into the ischemic territory through holes 412 a, b and c.

The sub-microcatheter 200 may include more or fewer holes than the three shown. The holes may be linearly arranged or may be staggered.

The extracorporeal circuit 100 may include a conventional microcatheter, such as is shown at 50 in Figure 4 or a conventional microcatheter with sideholes 360. With the microcatheters 50 and 360, shown in Fig. 5, thrombolytic drugs are delivered to the clot 8 through the annular orifice 221 defined by an outer annular wall of the sub-microcatheter 200 and inner wall 225 of the microcatheters 50 and 360. With the microcatheter 360, drugs may additionally be delivered through sideholes 340 a-c. The extracorporeal circuit 100 may include the microcatheter 210 with sideholes 220 a, b, c, d, e, and f. Infusion of lytic drugs can be performed with a syringe 314 as well as other infusion devices.

Example 2 A reperfusion circuit 500, shown in Fig. 9 operates as described for the circuit 100 described in Fig. 6 except that the circuit 500 further includes the oxygenator 320.

Example 3 A reperfusion circuit 600 shown in Fig. 8 transports oxygenated blood or a blood substitute from the syringe 330 to the sub-microcatheter 200 without use of a pump or a closed loop.

Those skilled in the art will further appreciate that the present invention may be embodied in other specific forms without departing from the spirit or central attributes thereof. In that the foregoing description of the present invention discloses only exemplary embodiments thereof, it is to be understood that other variations are contemplated as being within the scope of the present invention. Accordingly, the present invention is not limited in the particular embodiments which have been described in detail therein. Rather, reference should be made to the appended claims as indicative of the scope and content of the present invention.

Claims

What is claimed is:
1. A method for providing oxygenated blood or a blood substitute to brain tissue and to brain blood vessels starved for oxygen as a result of a thrombus formation or embolic stroke, comprising: providing a sub-microcatheter, comprising: a unitary, flexible main body defining a lumen and having a distal end and a proximal end wherein the main body defines a plurality of ports positioned proximally to the distal end; and an infusion hub positioned proximally to the plurality of ports; positioning the sub-microcatheter so that the plurality of ports are distal with respect to the thrombus; perfusing oxygenated blood or an oxygenated blood substitute through the ports into the brain tissue and brain blood vessels starved as a result of thrombus formation; and adjusting the temperature of the blood or blood substitute.
2. The method of claim 1 wherein the blood or blood substitute is adjusted to a cooler temperature.
3. The method of claim 1 wherein the temperature of the blood or blood substitute is adjusted prior to oxygenating the blood.
4. The method of claim 1 wherein the temperature is adjusted with a feedback control scheme.
5. The method of claim 1 wherein the temperature is adjusted with a feed forward control scheme.
6. The method of claim 1 wherein the temperature is adjusted with a feed forward- feedback control scheme.
7. A sub-microcatheter, comprising: a unitary, flexible main body defining a lumen and having a distal end and a proximal end wherein the main body defines a plurality of ports positioned proximally to the distal end; and an infusion hub positioned proximally to the plurality of ports.
8. A sub-microcatheter-microcatheter combination comprising: a sub-microcatheter comprising a unitary, flexible main body defining a lumen and having a distal end and a proximal end wherein the main body defines a plurality of ports positioned proximally to the distal end; and an infusion hub positioned distally to the plurality of ports; a microcatheter comprising an annular main body, positioned annularly about at least a portion of the sub-microcatheter, the microcatheter main body comprising an annular wall defining a plurality of ports, the microcatheter main body terminating distally and annularly about the main body of the sub-microcatheter wherein the submicrocatheter has a length effective for spanning and passing through a vessel obstruction.
9. The combination of claim 6 wherein the microcatheter is annularly sealed about the main body of the sub-microcatheter.
10. The combination of claim 6 and further including a mandril moveably positioned within the sub-microcatheter.
11. The combination of claim 8 wherein the mandril includes a tapered section.
12. A microcatheter comprising a main body with a distal end that terminates in an annular wall defining an orifice, the annular wall effective for forming a seal with another annular wall.
13. The microcatheter of claim 10 wherein the main body defines one or more side holes.
14. A re-perfusion circuit, comprising: a source of blood or a blood substitute; a conduit for receiving the blood or blood substitute, the conduit comprising a side arm; and a sub-microcatheter with a side hub for receipt of the blood or blood substitute from the conduit wherein the sub-microcatheter is of a length effective for spanning and passing through a vessel obstruction.
15. The re-perfusion circuit of claim 12 and further including a pump for pumping the blood or blood substitute from the conduit to the sub-microcatheter.
16. The re-perfusion circuit of claim 12 and further including an oxygenator for oxygenating the blood or blood substitute.
17. The re-perfusion circuit of claim 12 and further including a microcatheter in which the sub-microcatheter is at least partially positioned.
18. The re-perfusion circuit of claim 12 wherein the sub-microcatheter defines holes for passage of the blood or blood substitute into an ischemic territory.
19. The re-perfusion circuit of claim 15 wherein the microcatheter encloses holes for anti- thromic drugs.
20. The re-perfusion circuit of claim 12 and further including a sheath with a side arm for receipt of blood from a living being.
21. The re-perfusion circuit of claim 12 and further including a heat exchanger for adjusting temperature of the blood or blood substitute.
22. The re-perfusion circuit of claim 19 and further including a temperature sensor.
23. The re-perfusion circuit of claim 20 and further including a controller in communication with the temperature sensor.
24. The re-perfusion circuit of claim 12 wherein the blood substitute is selected from a group consisting of blood substitutes comprising fluorocarbons, nitric oxide, super- oxygenated saline, neuroprotectants, modified or synthetic constructs of hemoglobulin, ions, genes and gene fragments, nitric oxide donors , nitric oxide inhibitors, calcium chelating compounds, iron chelating compounds, growth factors, streroids, and tissue edema reductants.
PCT/US1999/020100 1998-09-08 1999-09-03 Method for re-perfusion of oxygenated blood WO2000013734A2 (en)

Priority Applications (6)

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US9947498P true 1998-09-08 1998-09-08
US60/099,474 1998-09-08
US12684199P true 1999-03-31 1999-03-31
US60/126,841 1999-03-31
US37440299A true 1999-08-13 1999-08-13
US09/374,402 1999-08-13

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AU61343/99A AU6134399A (en) 1998-09-08 1999-09-03 Method for re-perfusion of oxygenated blood

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US6622367B1 (en) 1998-02-03 2003-09-23 Salient Interventional Systems, Inc. Intravascular device and method of manufacture and use
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EP2740511A1 (en) * 2012-12-07 2014-06-11 Covidien LP Microcatheter

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AU6134399A (en) 2000-03-27
WO2000013734A3 (en) 2000-07-13

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