Surgery: light – thermal – and electrical application – Light – thermal – and electrical application – Thermal applicators
Reexamination Certificate
2000-11-16
2002-11-12
Kearney, Rosiland S. (Department: 3739)
Surgery: light, thermal, and electrical application
Light, thermal, and electrical application
Thermal applicators
C607S106000, C607S113000, C606S021000, C128S898000
Reexamination Certificate
active
06478811
ABSTRACT:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not Applicable
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the modification and control of optimal temperatures for enzymes. More particularly, the invention relates to the modification and control of optimal temperatures for enzymes for use in treatments such as thrombolysis.
2. Background Information
Organs in the human body, such as the brain, kidney and heart, are maintained at a constant temperature of approximately 37° C. Hypothermia can be clinically defined as a core body temperature of 35° C. or less. Hypothermia is sometimes characterized further according to its severity. A body core temperature in the range of 33° C. to 35° C. is described as mild hypothermia. A body temperature of 28° C. to 32° C. is described as moderate hypothermia. A body core temperature in the range of 24° C. to 28° C. is described as severe hypothermia.
Hypothermia is uniquely effective in reducing brain injury caused by a variety of neurological insults and may eventually play an important role in emergency brain resuscitation. Experimental evidence has demonstrated that cerebral cooling improves outcome after global ischemia, focal ischemia, or traumatic brain injury. For this reason, hypothermia may be induced in order to reduce the effect of certain bodily injuries to the brain as well as other organs.
Cerebral hypothermia has traditionally been accomplished through whole body cooling to create a condition of total body hypothermia in the range of 20° C. to 30° C. However, the use of total body hypothermia risks certain deleterious systematic vascular effects. For example, total body hypothermia may cause severe derangement of the cardiovascular system, including low cardiac output, elevated systematic resistance, and ventricular fibrillation. Other side effects include renal failure, disseminated intravascular coagulation, and electrolyte disturbances. In addition to the undesirable side effects, total body hypothermia is difficult to administer.
Catheters have been developed which are inserted into the bloodstream of the patient in order to induce total body hypothermia. For example, U.S. Pat. No. 3,425,419 to Dato describes a method and apparatus of lowering and raising the temperature of the human body. Dato induces moderate hypothermia in a patient using a metallic catheter. The metallic catheter has an inner passageway through which a fluid, such as water, can be circulated. The catheter is inserted through the femoral vein and then through the inferior vena cava as far as the right atrium and the superior vena cava. The Dato catheter has an elongated cylindrical shape and is constructed from stainless steel. By way of example, Dato suggests the use of a catheter approximately 70 cm in length and approximately 6 mm in diameter. However, use of the Dato device implicates the negative effects of total body hypothermia described above.
Due to the problems associated with total body hypothermia, attempts have been made to provide more selective cooling. For example, cooling helmets or head gear have been used in an attempt to cool only the head rather than the patient's entire body. However, such methods rely on conductive heat transfer through the skull and into the brain. One drawback of using conductive heat transfer is that the process of reducing the temperature of the brain is prolonged. Also, it is difficult to precisely control the temperature of the brain when using conduction due to the temperature gradient that must be established externally in order to sufficiently lower the internal temperature. In addition, when using conduction to cool the brain, the face of the patient is also subjected to severe hypothermia, increasing discomfort and the likelihood of negative side effects. It is known that profound cooling of the face can cause similar cardiovascular side effects as total body cooling. From a practical standpoint, such devices are cumbersome and may make continued treatment of the patient difficult or impossible.
Selected organ hypothermia has been accomplished using extracorporeal perfusion, as detailed by Arthur E. Schwartz, M.D. et al., in Isolated Cerebral Hypothermia by Single Carotid Artery Perfusion of Extracorporeally Cooled Blood in Baboons, which appeared in Vol. 39, No. 3, NEUROSURGERY 577 (September, 1996). In this study, blood was continually withdrawn from baboons through the femoral artery. The blood was cooled by a water bath and then infused through a common carotid artery with its external branches occluded. Using this method, normal heart rhythm, systemic arterial blood pressure and arterial blood gas values were maintained during the hypothermia. This study showed that the brain could be selectively cooled to temperatures of 20° C. without reducing the temperature of the entire body. However, external circulation of blood is not a practical approach for treating humans because the risk of infection, need for anticoagulation, and risk of bleeding is too great. Further, this method requires cannulation of two vessels making it more cumbersome to perform particularly in emergency settings. Even more, percutaneous cannulation of the carotid artery is difficult and potentially fatal due to the associated arterial wall trauma. Finally, this method would be ineffective to cool other organs, such as the kidneys, because the feeding arteries cannot be directly cannulated percutaneously.
Selective organ hypothermia has also been attempted by perfusion of a cold solution such as saline or perflourocarbons. This process is commonly used to protect the heart during heart surgery and is referred to as cardioplegia. Perfusion of a cold solution has a number of drawbacks, including a limited time of administration due to excessive volume accumulation, cost, and inconvenience of maintaining the perfusate and lack of effectiveness due to the temperature dilution from the blood. Temperature dilution by the blood is a particular problem in high blood flow organs such as the brain.
Selective organ hypothermia is useful in limiting brain injury after ischemia or traumatic brain injury, as noted above. For example, neurons subjected to ischemia may die. Selective cooling of these neurons, such as by nerve cooling, has been shown to increase the survival rate. Hypothermic temperatures which may be employed include, e.g., 20° C. to 35° C.
Ischemia is blockage of the arteries that supply blood to a tissue. The blockage itself is referred to as a clot or thrombus and results from the solidification of fibrinogen into fibrin. A stroke is ischemia where the arteries to the brain are blocked. In a stroke, the clot forms in the cerebral or pre-cerebral arteries. This type of blockage may also be caused by a thrombus that breaks free from the heart and flows into an artery through which it cannot pass. In other words, the thrombus gets lodged in the artery.
Clots can be treated in several ways. One way, fibrinolysis, employs enzymes that lyse, or break up and dissolve, the clot. Thrombolysis is fibrinolysis used to treat thrombosed vessels. The enzymes that lyse clots are termed thrombolytics because thrombin is the enzyme that coagulates fibrinogen. Streptokinase(“SK”), urokinase (“UK”), and tissue plasminogen activator (“tPA”) are thrombolytics and are often used in this capacity. These enzymes can be given as drugs by intravenous injection or by intra-arterial delivery using a catheter with a fluid outlet port near or at the site of the clot.
Drug administration is occasionally problematic as some sensitive patients encounter adverse reactions to drugs. Moreover, there is a risk of hemorrhage when these drugs are given intravenously. There is a need for a method of lysing clots that does not rely solely or partially on drug administration. There is further a need for a method of lysing clots in which the effects of ischemia on affected cells is minimized.
In some cases, of course, the extent or nature of the clot indicates that drug therapies must be used.
Dobak III John D.
Lasheras Juan C.
Innercool Therapies, Inc
Kearney Rosiland S.
Wieczorek Mark D.
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