US 6,325,818 B1Grant

Inflatable cooling apparatus for selective organ hypothermia

Issue Date:2001-12-04

•11 Claims

•2 Drawing Sheets

Abstract

A cooling apparatus having an inflatable balloon near a distal end of a multi-lumen catheter, with a plurality of blood flow passageways formed through the interior of the balloon from a proximal face of the inflated balloon to a distal face of the inflated balloon. Chilled saline solution is introduced through a supply lumen of the catheter to inflate the balloon in a feeding artery of the selected organ; this allows blood to flow through the blood flow passageways of the balloon, from one exterior face of the balloon to another exterior face. The saline solution continues to circulate around the blood flow passageways inside the balloon, to cool the blood, eventually exiting the balloon through a return lumen of the catheter.

Metadata

Assignee

Innercool Therapies, Inc.

Inventor

Randell Werneth

Application Information

Application Number:US 09/414,184

Filing Date:1999-10-07

Priority Date:1999-10-07

Art Unit:7

Classifications

IPC:

A61F 700

Field of Search:

607113607105607106606 21606 23604 960160410306604113

Patent Drawings (2 sheets)

Description

Background of the Invention

[0002] 1. Field of the Invention

[0003] The current invention relates to selective cooling, or hypothermia, of an organ, such as the brain, by cooling the blood flowing into the organ. This cooling can protect the tissue from injury caused by anoxia or trauma.

[0004] 2. Background Information

[0005] Organs of the human body, such as the brain, kidney, and heart, are maintained at a constant temperature of approximately 37° C. Cooling of organs below 35° C. is known to provide cellular protection from anoxic damage caused by a disruption of blood supply, or by trauma. Cooling can also reduce swelling associated with these injuries.

[0006] Hypothermia is currently utilized in medicine and is sometimes performed to protect the brain from injury. Cooling of the brain is generally accomplished through whole body cooling to create a condition of total body hypothermia in the range of 20° to 30° C. This cooling is accomplished by immersing the patient in ice, by using cooling blankets, or by cooling the blood flowing externally through a cardiopulmonary bypass machine.

[0007] Total body hypothermia to provide organ protection has a number of drawbacks. First, it creates cardiovascular problems, such as cardiac arhythmias, reduced cardiac output, and increased systemic vascular resistance. These side effects can result in organ damage. These side effects are believed to be caused reflexively in response to the reduction in core body temperature. Second, total by hypothermia is difficult to administer. Immersing a patient in ice water clearly has its associated problems. Placement on cardiopulmonary bypass requires surgical intervention and specialists to operate the machine, and it is associated with a number of complications including bleeding and volume overload. Third, the time required to reduce the body temperature and the organ temperature is prolonged. Minimizing the time between injury and the onset of cooling has been shown to produce better clinical outcomes.

[0008] Some physicians have immersed the patient's head in ice to provide brain cooling. There are also cooling helmets, or head gear, to perform the same. This approach suffers from the problems of slow cool down and poor temperature control due to the temperature gradient that must be established externally to internally. It has also been shown that complications associated with total body cooling, such as arrhythmia and decreased cardiac output, can also be caused by cooling of the face and head only.

[0009] Selective organ hypothermia has been studied by Schwartz, et. al. Utilizing baboons, blood was circulated and cooled externally from the body via the femoral artery and returned to the body through the carotid artery. This study showed that the brain could be selectively cooled to temperatures of 20° C. without reducing the temperature of the entire body. Subsequently, cardiovascular complications associated with total body hypothermia did not occur. However, external circulation of the blood for cooling is not a practical approach for the treatment of humans. The risks of infection, bleeding, and fluid imbalance are great. Also, at least two arterial vessels must be punctured and cannulated. Further, percutaneous cannulation of the carotid artery is very difficult and potentially fatal, due to the associated arterial wall trauma. Also, this method could not be used to cool organs such as the kidneys, where the renal arteries cannot be directly cannulated percutaneously.

[0010] Selective organ hypothermia has also been attempted by perfusing the organ with a cold solution, such as saline or perflourocarbons. This is commonly done to protect the heart during heart surgery and is referred to as cardioplegia. This procedure has a number of drawbacks, including limited time of administration due to excessive volume accumulation, cost and inconvenience of maintaining the perfusate, and lack of effectiveness due to temperature dilution from the blood. Temperature dilution by the blood is a particular problem in high blood flow organs such as the brain. For cardioplegia, the blood flow to the heart is minimized, and therefore this effect is minimized.

[0011] Intravascular, selective organ hypothermia, created by cooling the blood flowing into the organ, is the ideal method. First, because only the target organ is cooled, complications associated with total body hypothermia are avoided. Second, because the blood is cooled intravascularly, or in situ, problems associated with external circulation of blood are eliminated. Third, only a single puncture and arterial vessel cannulation is required, and it can be performed at an easily accessible artery such as the femoral, subclavian, or brachial. Fourth, cold perfusate solutions are not required, thus eliminating problems with excessive fluid accumulation. This also eliminates the time, cost, and handling issues associated with providing and maintaining cold perfusate solution. Fifth, rapid cooling can be achieved. Sixth, precise temperature control is possible.

[0012] The important factor related to catheter development for selective organ hypothermia is the small size of the typical feeding artery, and the need to prevent a significant reduction in blood flow when the catheter is placed in the artery. A significant reduction in blood flow would result in ischemic organ damage. While the diameter of the major vessels of the body, such as the vena cava and aorta, are as large as 15 to 20 mm., the diameter of the feeding artery of an organ is typically only 4.0 to 8.0 mm. Thus, a catheter residing in one of these arteries cannot be much larger than 2.0 to 3.0 mm. in outside diameter. The small size of the feeding artery also limits the size and type of heat transfer element that can safely be used.

[0013] A catheter based on the circulation of water or saline operates on the principle of transferring heat from the blood to raise the temperature of the water. Therefore, it is essential to use a heat transfer element that transfers heat from the blood to the cooling fluid as efficiently as possible, while restricting the flow of blood as little as possible. So, it would be beneficial to have a heat transfer apparatus that can be inserted percutaneously into an artery of restricted size, that can efficiently transfer heat, and that will not significantly limit the flow rate of blood in the artery during application of cooling.

Brief Summary of the Invention

[0014] The present invention is a cooling apparatus comprising a flexible catheter which can be inserted through the vascular system of a patient to a feeding artery, with an inflatable balloon heat exchanger near the distal end of the catheter. The present invention also encompasses a method for using such a device to perform selective organ cooling. After placement in the selected feeding artery, the heat exchanger balloon is inflated by pressurization with a saline solution, via a supply lumen in the catheter. The heat exchanger balloon has one or more blood passageways passing through it, from a proximal aspect of the balloon to a distal aspect of the balloon. When the heat exchanger balloon is inflated to contact the wall of the artery in which it is placed, each of the blood passageways comprises a tube having an inlet in one face of the heat exchanger balloon and an outlet in another face of the heat exchanger balloon, thereby allowing blood to continue flowing through the artery after inflation of the balloon. The blood passageway tubes can be constructed of a material having a relatively high thermal conductivity, such as a thin metallized polymer, such as a film with one or more metallized surfaces. Alternatively, the blood passageway tubes can be constructed of a metal-loaded polymer film. Further, the entire heat exchanger balloon can be constructed of such a material, in order to maximize the cooling capacity of the heat exchanger.

[0015] After inflation of the heat exchanger balloon, the saline solution, which is chilled by an external chiller, continues circulating through the interior of the heat exchanger balloon, around the blood passageway tubes, and back out of the balloon through a return lumen in the catheter. This cools the blood passageway tubes, which in turn cool the blood flowing through them. This cooled blood then flows through the selected organ and cools the organ.

[0016] The device can also incorporate a lumen for a guidewire, facilitating the navigation of the catheter through the vascular system of the patient.

[0017] The novel features of this invention, as well as the invention itself, will be best understood from the attached drawings, taken along with the following description, in which similar reference characters refer to similar parts, and in which:

Brief Description of the Several Views of the Drawings

[0018] FIG. 1 is a perspective view of the device of the present invention in place in a common carotid artery of a patient;

[0019] FIG. 2 is a perspective view of the device shown in FIG. 1, with additional details of construction;

[0020] FIG. 3 is a transverse section view of the device shown in FIG. 2, along the section line 3—3; and

[0021] FIG. 4 is a partial longitudinal section view of the device shown in FIG. 2, showing the flow path of the cooling fluid.

Detailed Description of the Invention

[0022] As shown in FIG. 1, the cooling apparatus 10 of the present invention includes a flexible multilumen catheter 12, an inflatable balloon 14, and a plurality of blood flow passageways 16 through the balloon 14. The balloon 14 is shown in an inflated state, in a selected position in a common carotid artery CC.

[0023] The balloon 14 is attached near a distal end of the flexible catheter 12. The catheter 12 can have at least a cooling fluid supply lumen 18 and a cooling fluid return lumen 20, with the cooling fluid supply lumen 18 preferably being located substantially within the cooling fluid return lumen 20. The catheter 12 can also have a guidewire lumen 22, for the passage of a guidewire 24, as is known in the art.

[0024] The balloon 14 can be formed from a flexible material, such as a polymer. The balloon 14 can be constructed to assume a substantially cylindrical shape when inflated, with a proximal aspect 15 and a distal aspect 17. The balloon 14 can have a plurality of tubular shaped blood flow passageways 16 formed therethrough, from the proximal aspect 15 to the distal aspect 17. The tubular walls of the passageways 16 constitute a heat transfer surface, for transferring heat from the blood to the cooling fluid. The flexible material of the tubular passageways 16 can be, at least in part, a metallized material, such as a film coated with a thin metal layer, either internally, externally, or both, to aid in heat transfer through the passageway walls. Alternatively, the tubular passageways 16 can be constructed of a metal-loaded polymer film. Further, the remainder of the balloon 14 can be coated with a thin metallized layer, either internally, externally, or both, or a metal-loaded polymer film. The proximal aspect 15 and the distal aspect 17 of the balloon can also constitute a heat transfer surface, for transferring heat from the blood to the cooling fluid. The guidewire lumen 22 of the catheter 12 can also pass through the balloon 14, from the proximal aspect 15 to the distal aspect 17.

[0025] As shown in FIG. 2, each tubular passageway 16 has a proximal port 26 in a proximal face 28 on the proximal aspect 15 of the balloon 14, and a distal port 30 in a distal face 32 on the distal aspect 17 of the balloon 14. A cooling fluid supply port 34 near the distal end of the cooling fluid supply lumen 18 supplies chilled saline solution from a chiller (not shown) to the interior of the balloon 14, surrounding the blood flow passageways 16. A cooling fluid return port 36 in the cooling fluid return lumen 20 returns the saline solution from the interior of the balloon 14 to the chiller. Relative placement of the cooling fluid ports 34, 36 can be chosen to establish flow counter to the direction of blood flow, if desired.

[0026] FIG. 3 shows the proximal aspect 15 of the balloon 14 and gives a view through the blood flow passageways 16, illustrating the general arrangement of the blood flow passageways 16, cooling fluid supply lumen 18, cooling fluid return lumen 20, and guidewire lumen 22, within the outer wall 38 of the balloon 14. FIG. 4 is a side elevation view of the apparatus 10, with a partial longitudinal section through the balloon wall 38, showing one possible arrangement of the cooling fluid supply port 34 and the cooling fluid return port 36 within the balloon 14.

[0027] In practice, the balloon 14, in a deflated state, is passed through the vascular system of a patient on the distal end of the catheter 12, over the guidewire 24. Placement of the guidewire 24 and the balloon 14 can be monitored fluoroscopically, as is known in the art, by use of radiopaque markers (not shown) on the guidewire 24 and the balloon 14. When the balloon 14 has been positioned at a desired location in the feeding artery of a selected organ, such as in the common carotid artery feeding the brain, fluid such as saline solution is supplied through the cooling fluid supply lumen 18. This fluid passes trough the cooling fluid supply port 34 into the interior of the balloon 14, surrounding the tubular passageways 16, to inflate the balloon 14. Although the balloon 14 can be formed to assume a substantially cylindrical shape upon unconstrained inflation, the balloon 14 will essentially conform to the shape of the artery within which it is inflated. As the balloon 14 inflates, the blood flow passageways 16 open, substantially assuming the tubular shape shown.

[0028] When the balloon 14 has been properly inflated, blood continues to flow through the feeding artery CC by flowing through the blood flow passageways 16, as indicated, for example, by the arrows in FIG. 1. The size and number of the blood flow passageways 16 are designed to provide a desired amount of heat transfer surface, while maintaining a suitable amount of blood flow through the feeding artery CC. Return flow to the chiller can be established, to allow flow of cooling fluid through the cooling fluid return port 36 and the cooling fluid return lumen 20 to the chiller. This establishes a continuous flow of cooling fluid through the interior of the balloon 14, around the blood flow passageways 16. The return flow is regulated to maintain the balloon 14 in its inflated state, while circulation of cooling fluid takes place. The saline solution is cooled in the chiller to maintain a desired cooling fluid temperature in the interior of the balloon 14, to impart a desired temperature drop to the blood flowing through the tubular passageways 16. This cooled blood flows through the feeding artery to impart the desired amount of cooling to the selected organ. Then, cooling fluid can be evacuated or released from the balloon 14, through the catheter 12, to deflate the balloon 14, and the apparatus 10 can be withdrawn from the vascular system of the patient.

[0029] While the particular invention as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages hereinbefore stated, it is to be understood that this disclosure is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended other than as described in the appended claims.

Claims

I claim:

1. A cooling apparatus for selective organ hypothermia, comprising:

a flexible catheter;

an inflatable balloon attached near a distal end of said catheter;

at least one blood flow passageway formed through the interior of said balloon, said at least one blood flow passageway extending from a proximal blood flow port in a proximal exterior face of said balloon to a distal blood flow port in a distal exterior face of said balloon;

a cooling fluid supply lumen formed in said catheter;

a cooling fluid supply port in said catheter, connecting said cooling fluid supply lumen to the interior of said balloon;

a cooling fluid return lumen formed in said catheter; and

a cooling fluid return port in said catheter, connecting the interior of said balloon to said cooling fluid return lumen;

wherein said at least one blood flow passageway is formed from a metallized polymer film.

2. A cooling apparatus as recited in claim 1, wherein said balloon is inflatable to a substantially cylindrical shape.

3. A cooling apparatus as recited in claim 1, wherein said at least one blood flow passageway assumes a substantially tubular shape upon inflation of said balloon.

4. A cooling apparatus as recited in claim 1, further comprising a guidewire lumen formed in said catheter.

5. A cooling apparatus as recited in claim 1, further comprising a plurality of blood flow passageways formed through the interior of said balloon, each said blood flow passageway extending from a proximal blood flow port in a proximal exterior face of said balloon to a distal blood flow port in a distal exterior face of aid balloon.

6. A cooling apparatus as recited in claim 1, wherein said at least one blood flow passageway is formed from a polymer film having metal layers formed on both interior and exterior surfaces.

7. A cooling apparatus as recited in claim 1, wherein said at least one blood flow passageway is formed from a polymer film loaded with metal particles.

8. A cooling apparatus for selective organ hypothermia, comprising:

a flexible catheter;

an inflatable balloon attached near a distal end of said catheter, said balloon being inflatable to a substantially cylindrical shape;

a plurality of blood flow passageways formed through the interior of said balloon, each said blood flow passageway extending from a proximal blood flow port in a proximal exterior face of said balloon to a distal blood flow port in a distal exterior face of said balloon, each said blood flow passageway being shaped to assume a substantially tubular shape upon inflation of said balloon, each said blood flow passageway being formed of a material having high thermal conductivity;

a cooling fluid supply lumen formed in said catheter;

a cooling fluid supply port in said catheter, connecting said cooling fluid supply lumen to the interior of said balloon;

a cooling fluid return lumen formed in said catheter; and

a cooling fluid return port in said catheter, connecting the interior of said balloon to said cooling fluid return lumen;

wherein each said blood flow passageway is formed from a metallized polymer film.

9. A cooling apparatus as recited in claim 8, wherein each said blood flow passageway is formed from a polymer film having metal layers formed on both interior and exterior surfaces.

10. A cooling apparatus as recited in claim 8, further comprising a guidewire lumen formed in said catheter.

11. A cooling apparatus as recited in claim 8, wherein each said blood flow passageway is formed from a polymer film loaded with metal particles.

Patent Citations (146)

Patent	Date	Inventor	Cited By
US2308484	1943-01-01	Auzin et al.	Applicant
US2374609	1945-04-01	McCollum	Applicant
US2615686	1952-10-01	Davidson	Applicant
US2672032	1954-03-01	Towse	Applicant
US2913009	1959-11-01	Kuthe	Applicant
US3298371	1967-01-01	Lee	Applicant
US3425419	1969-02-01	Dato	Applicant
US3504674	1970-04-01	Swenson et al.	Applicant
US3865116	1975-02-01	Brooks	Applicant
US3888259	1975-06-01	Miley	Applicant
US3971383	1976-07-01	Van Gerven	Applicant
US4038519	1977-07-01	Foucras	Applicant
US4153048	1979-05-01	Magrini	Applicant
US4190033	1980-02-01	Foti	Applicant
US4231425	1980-11-01	Engstrom	Applicant
US4275734	1981-06-01	Mitchiner	Applicant
US4298006	1981-11-01	Parks	Applicant
US4318722	1982-03-01	Altman	Applicant
US4427009	1984-01-01	Wells et al.	Applicant
US4445500	1984-05-01	Osterholm	Applicant
US4483341	1984-11-01	Witteles	Applicant
US4502286	1985-03-01	Okada et al.	Applicant
US4569355	1986-02-01	Bitterly	Applicant
US4581017	1986-04-01	Sahota	Applicant
US4655746	1987-04-01	Daniels et al.	Applicant
US4672962	1987-06-01	Hershenson	Applicant
US4748979	1988-06-01	Hershenson	Applicant
US4750493	1988-06-01	Brader	Applicant
US4762130	1988-08-01	Fogarty et al.	Applicant
US4860744	1989-08-01	Johnson et al.	Applicant
US4883455	1989-11-01	Leonard	Applicant
US4894164	1990-01-01	Polaschegg	Applicant
US4904237	1990-02-01	Janese	Applicant
US4920963	1990-05-01	Brader	Applicant
US4964409	1990-10-01	Tremulis	Applicant
US5000734	1991-03-01	Boussignac et al.	Examiner
US5014695	1991-05-01	Benak et al.	Applicant
US5018521	1991-05-01	Campbell	Applicant
US5019075	1991-05-01	Spears et al.	Applicant
US5041089	1991-08-01	Mueller et al.	Applicant
US5078713	1992-01-01	Varney	Applicant
US5092841	1992-03-01	Spears	Applicant
US5106360	1992-04-01	Ishwara et al.	Applicant
US5108390	1992-04-01	Potocky et al.	Applicant
US5110721	1992-05-01	Anaise et al.	Applicant
US5117822	1992-06-01	Laghi	Applicant
US5147355	1992-09-01	Friedman et al.	Applicant
US5149321	1992-09-01	Klatz et al.	Applicant
US5150706	1992-09-01	Cox et al.	Applicant
US5151100	1992-09-01	Abele et al.	Applicant
US5190539	1993-03-01	Fletcher et al.	Applicant
US5191883	1993-03-01	Lennox et al.	Applicant
US5196024	1993-03-01	Barath	Applicant
US5211631	1993-05-01	Sheaff	Applicant
US5234405	1993-08-01	Klatz et al.	Applicant
US5248312	1993-09-01	Langberg	Applicant
US5250070	1993-10-01	Parodi	Applicant
US5257977	1993-11-01	Eshel	Applicant
US5264260	1993-11-01	Saab	Applicant
US5269369	1993-12-01	Faghri	Applicant
US5269749	1993-12-01	Koturov	Applicant
US5269758	1993-12-01	Taheri	Applicant
US5281213	1994-01-01	Milder et al.	Applicant
US5281215	1994-01-01	Milder	Applicant
US5310440	1994-05-01	Zingher	Applicant
US5334193	1994-08-01	Nardella	Applicant
US5342301	1994-08-01	Saab	Applicant
US5344436	1994-09-01	Fontenot et al.	Applicant
US5365750	1994-11-01	Greenthal	Applicant
US5368591	1994-11-01	Lennox et al.	Applicant
US5383918	1995-01-01	Panetta	Applicant
US5395314	1995-03-01	Klatz et al.	Applicant
US5395331	1995-03-01	O'Neill et al.	Applicant
US5403281	1995-04-01	O'Neill et al.	Applicant
US5417686	1995-05-01	Peterson et al.	Applicant
US5423745	1995-06-01	Todd et al.	Applicant
US5423807	1995-06-01	Milder	Applicant
US5433740	1995-07-01	Yamaguchi	Applicant
US5437673	1995-08-01	Baust et al.	Applicant
US5462521	1995-10-01	Brucker et al.	Applicant
US5486204	1996-01-01	Clifton	Applicant
US5486208	1996-01-01	Ginsburg	Applicant
US5531776	1996-07-01	Ward et al.	Applicant
US5558644	1996-09-01	Boyd et al.	Applicant
US5573532	1996-11-01	Chang et al.	Applicant
US5578008	1996-11-01	Hara	Examiner
US5584804	1996-12-01	Klatz et al.	Applicant
US5588438	1996-12-01	McKown et al.	Applicant
US5591162	1997-01-01	Fletcher et al.	Applicant
US5620480	1997-04-01	Rudie	Applicant
US5624392	1997-04-01	Saab	Examiner
US5643197	1997-07-01	Brucker et al.	Applicant
US5647051	1997-07-01	Neer	Applicant
US5653692	1997-08-01	Masterson et al.	Examiner
US5713941	1998-02-01	Robins et al.	Applicant
US5716386	1998-02-01	Ward et al.	Applicant
US5735809	1998-04-01	Gorsuch	Applicant
US5797878	1998-08-01	Bleam	Applicant
US5800480	1998-09-01	Augustine et al.	Applicant
US5807391	1998-09-01	Wijkamp	Applicant
US5824030	1998-10-01	Yang et al.	Applicant
US5827222	1998-10-01	Klatz et al.	Applicant
US5827237	1998-10-01	Macoviak et al.	Applicant
US5833671	1998-11-01	Macoviak et al.	Applicant
US5837003	1998-11-01	Ginsburg	Applicant
US5871526	1999-02-01	Gibbs et al.	Applicant
US5873835	1999-02-01	Hastings et al.	Applicant
US5879329	1999-03-01	Ginsburg	Applicant
US5899899	1999-05-01	Arless et al.	Applicant
US5902268	1999-05-01	Saab	Applicant
US5913885	1999-06-01	Klatz et al.	Applicant
US5913886	1999-06-01	Soloman	Applicant
US5916242	1999-06-01	Schwartz	Applicant
US5957963	1999-09-01	Dobak, III	Applicant
US5989238	1999-11-01	Ginsburg	Applicant
US6019783	2000-02-01	Phillips	Applicant
US6033383	2000-03-01	Ginsburg	Examiner
US6042559	2000-03-01	Dobak	Applicant
US6051019	2000-04-01	Dobak, III	Applicant
US6096068	2000-08-01	Dobak, III et al.	Applicant
US6110168	2000-08-01	Ginsburg	Applicant
US6126684	2000-10-01	Ginsburg et al.	Applicant
EP655225A1	1993-05-01		Applicant
EP664990	1997-11-01		Applicant
FR2447406	1980-03-01		Applicant
SU806029	1981-02-01		Applicant
WO91/05528	1991-05-01		Applicant
WO93/04727	1993-03-01		Applicant
WO95/01814	1995-01-01		Applicant
WO96/40347	1996-12-01		Applicant
WO97/01374	1997-01-01		Applicant
WO97/25011	1997-07-01		Applicant
WO98/26831	1998-06-01		Applicant
WO98/31312	1998-07-01		Applicant
WO99/37226	1999-07-01		Applicant
WO99/48449	1999-09-01		Applicant
WO99/66970	1999-12-01		Applicant
WO99/66971	1999-12-01		Applicant
WO/09054	2000-02-01		Applicant
WO/10494	2000-02-01		Applicant
WO/38601	2000-06-01		Applicant
WO47145	2000-08-01		Applicant
WO/48670	2000-08-01		Applicant
WO/51534	2000-09-01		Applicant
WO/53135	2000-09-01		Applicant
WO/0057823	2000-10-01		Applicant

Non-Patent Literature (27)

Ambrus; The Biphasic Nature and Temperature Dependence of the Activation of Human Plasminogen by Urokinase; May 1979; pp. 339-347; Research Communications in Chemical Pathology and Pharmacology, vol. 24, No. 2.Applicant
Bigelo; Hypothermia, Its Possible Role in Cardiac Surgery; Nov. 1959; pp. 849-866; Annals of Surgery, vol. 132, No. 5.Applicant
Cheatle; Cryostripping the Long and Short Saphenous Veins; Jan. 1993; p. 1283; Br. J. Surg., vol. 80.Applicant
Dexter; Blood Warms as Its Blows Retrograde from a Femoral Cannulation Site to the Carotic Artery During Cardiopulmonary Bypass; Nov. 1994; pp. 393-397; Perfusion, vol. 9, No. 6.Applicant
Gillinov; Superior Cerebral Protection with Profound Hypothermia During Circulatory Arrest; Nov. 1992; pp. 1432-1439; Ann. Thorac. Surg., vol. 55.Applicant
Higazi; The Effect of Ultrasonic Irradiation and Temperature on Fibrinolytic Activity in Vitro; Aug. 1992; p. 251-253; Thrombosis Research, vol. 69, No. 2.Applicant
Imamaki; Retrograde Cerebral Perfusion with Hypothermic Blood Provides Efficient Protection of the Brain; Jul. 1995; pp. 325-333; Journal of Cardiac Surgery, vol. 10, No. 4, Part 1.Applicant
Jolin; Management of a Giant Intracranial Aneurysm Using Surface-Heparinized Extracorporeal Circulaiton and Controlled Deep Hypothermic Low Flow Perfusion; Aug. 1992; pp. 756-760; Acta Anaesthesiologica Scandinavia.Applicant
Jos R.C. Jansen, Ph.D., et al., Near Continuous Cardiac Output by Thermodilution, (1997), Journal of Clinical Monitoring 13:233-239.Applicant
Kimoto; Open Heart Surgery under Direct Vision with the Aid of Brain-Cooling by Irrigation; Jul. 1955; pp. 592-603; Surgery, vol. 39, No. 4.Applicant
Marekovic, Z; Abstract of Renal Ypothermia in Sistu by Venous Passages: Experimental Work on Dogs; 1980; Eur Urol 6(2); 1 page.Applicant
Meden; Effect of Hypothermia and Delayed Thrombolysis in a Rat Embolic Stroke Model; Dec. 1993; pp. 91-98; Acta Neurologica Scandinavica.Applicant
Meden; The Influence of Body Temperature on Infarct Volume and Thrombolytic Therapy in a Rat Embolic Stroke Model; Feb. 1994; pp. 131-138; Brain Research, vol. 647.Applicant
Milleret, Rene; La cryo-chirurgie danes les varices des mimbres inferieurs; Angiologie; Supplement au no. 110.Applicant
Milleret; Abstract of Cryosclerosis of the Saphenous Veins in Varicose Reflux in the Obese and Elderly; 10.1981; one page; Phlebologie, vol. 34, No. 4.Applicant
Parkins; Brain Cooling in the Prevention of Brain Damage During Periods of Circulatory Occlusion in Dogs; Apr. 1954; pp. 284-289; Annals of Surgery, vol. 140, No. 3.Applicant
Piepgras; Rapid Active Internal Core Cooling for Induction of Moderate Hypothermia in Head Injury by Use of an Extracorporeal Heat Exchanger; Feb. 1998; pp. 311-318; Neurosurgery, vol. 42, No. 2.Applicant
Rijken; Plasminogen Activation at Low Temperatures in Plasma Samples Containing Therapeutic Concentrations of Tissue-Type Plasminogen Activator or Other Thrombolytic Agents; Oct. 1989; pp. 47-52; place of publication unknown.Applicant
Schwartz, A.E. et al.; Isolated Cerebral Hypothermia by Single Carotid Artery Perfusion of Extracorporeally Cooled Blood in Baboons; (1996); Neurosurgery 39(3):577-582.Applicant
Schwartz; Cerebral Blood Flow During Low-flow Hypothermic Cardiopulmonary Bypass in Baboons; Jun. 1994; pp. 959-964; Anesthesiology, vol. 81, No. 4.Applicant
Schwartz; Selective Cerebral Hypothermia by Means of Transfemoral Internal Carotid Artery Catheterization; May 1996; pp. 571-572; Radiology, vol. 201, No. 2.Applicant
Steen; The Detrimental Effects of Prolonged Hypothermia and Rewarming in the Dog; Aug. 1979; pp. 224-230; Anesthesiology, vol. 52, No. 3.Applicant
Vandam; Hypothermia; Sep. 1959; pp. 546-553; The New England Journal of Medicine.Applicant
White; Cerebral Hypothermia and Circulatory Arrest; Jul. 1978, pp. 450-458; Mayo Clinic Proceedings, vol. 53.Applicant
Yenari; Thrombolysis with Tissue Plasminogen Activator (tPA) is Temperature Dependent; Jul. 1994; pp. 475-481; Thrombosis Research, vol. 77, No. 5.Applicant
Yoshihara; Changes in Coagulation and Fibrinolysis Occuring in Dogs during Hypothermia; Aug. 1984; pp. 503-512; Thrombosis Research, vol. 37, No. 4.Applicant
Zarins, Circulation in Profound Hypothermia; Nov. 1972; pp. 97-104; Journal of Surgical Research, vol. 14, N. 2.Applicant

Abstract