Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma heparin activity in 11 patients undergoing open-heart surgery was measured by comparing thrombin time of patient plasma to thrombin time of plasma containing known heparin concentrations. Although all patients received 300 units/kg of heparin, their initial plasma heparin levels varied significantly, from 1.8 units/ml in lighter petients to 3 units/ml in heavier patients. During hypothermia (25 degrees C), heparin decay was insignificant. At 37 degrees C, heparin decayed at a rate between 0.37 and 2.01 units/ml/hr. This decay was significantly faster in those patients with higher initial posthypothermia plasma heparin levels. When heparin was reversed with a protamine dose based on circulating plasma heparin levels, the mean difference between the predicted and the actual residual heparin activity was 0.025 units/ml. Heparin levels vary widely becuase of the influence of temperature on decay rates and because the space into which heparin is distributed is not simply proportional to weight. Evaluation and reversal of plasma heparin activity require ongoing analysis rather than any 1 dosage protocol.
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PMID:Plasma heparin activity and antagonism during cardiopulmonary bypass with hypothermia. 56 Jan 45

A method of heparinless, oxygenatorless, left heart bypass perfusion rewarming following surface hypothermia, with the use of a closed circuit with 130 ml. prime volume including heat exchanger, has been devised. The use of polyurethane-polyvinyl-graphite (PPG)-coated tubing has previously been reported. In this text, the use of an athrombogenic coating with cetyl-pyridinium chloride (CPC) as a regional heparin carrier was studied in dogs, comparing groups with PPG tubing and total systemic heparinization or plain polyvinyl tubing without systemic heparinization. Heparin compounded in the CPC coating eluted into the blood and caused mild transient whole-body heparinization during rewarming from 20 degrees to 25 degrees C., as evidenced by prolongation of the thrombin time. Alterations of hematologic parameters in all three groups were similar to those during surface rewarming except for those affected by heparinization. The left heart bypass method was found useful for hypothermic open-heart surgery when utilized with an athrombogenic surface coating or total body heparinization. It was concluded that the CPC coating is superior to the PPG coating since no cracking surface develops, it is translucent, and it provides a more effective athrombogenic surface.
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PMID:Use of athrombogenic tubing for perfusion rewarming following surface-induced deep hypothermia. 76 68

Abdominal multi-organ transplantation including the liver, gallbladder, spleen, pancreas, kidneys, adrenal glands and gastrointestinal tract was attempted in 8 dogs. Each experiment was discontinued when the recipient deteriorated. Immersion hypothermia was introduced in both the donor and recipient until the esophageal temperature reached 27-30 degrees C. Whole abdominal organs of the donor were removed in an en-bloc fashion at 20 degrees C of the graft temperature after additional cooling by ice slush scattering into the abdominal cavity. Transplantation was carried out orthotopically in the following sequence: (1) the proximal aorta, (2) suprahepatic vena cava, (3) distal aorta, (4) infrahepatic vena cava. The alimentary tract was reconstructed by gastro-gastrostomy and colo-colostomy. The ureters were implanted in the bladder. Cold ischemic time of the graft was about 40 minutes. Heparin was not used throughout the procedure. Five out of eight dogs were alive for more than 24 hours and two of them survived for 60 hours with good recovery. No immunosuppressant was given. Though the result in the present study was far from satisfaction, the experiment may provide a possibility of a new experimental model for transplantation, especially regarding pathophysiology and interrelationship of the transplanted complex organs.
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PMID:[Abdominal multi-organ transplantation in dogs]. 306 6

Beef lung heparin had substantially greater anticoagulant activity than pork mucosal heparin during a preoperative heparin tolerance test and also during cardiopulmonary bypass (CPB) in 100 randomized patients. Supplemental heparin was needed during CPB in many more of the patients receiving pork mucosal heparin. Heparin rebound was detected in 16 patients; this low incidence may result from a relatively high protamine:heparin ratio. There was notably less postoperative bleeding in those who received beef lung heparin. Platelet counts were not altered by either type of heparin. It is surprising that the preoperative tolerance curve only predicted heparin sensitivity during CPB in one-half of the patients. Blood activated coagulation time levels were increased markedly by hemodilution and further raised by hypothermia. These data demonstrate that beef lung heparin is better than pork mucosal heparin for CPB.
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PMID:A randomized study of beef lung and pork mucosal heparin in cardiac surgery. 634 19

Heparin, a polyanionic glycosaminoglycan, is used routinely before the induction of cardiopulmonary bypass. Earlier observations in our laboratory suggested that the postoperative bleeding that occurs, despite neutralization of heparin with protamine, is secondary to hypothermia and dilutional anemia during bypass. An additional, potential mechanism for excessive bleeding following cardiopulmonary bypass is that heparin activates the fibrinolytic system, which may, in turn, adversely affect hemostasis. To understand better the effects of heparin administration on the fibrinolytic system in vivo, we simulated the anticoagulant regimen of cardiopulmonary bypass by administering increasing doses of intravenous heparin to five adult baboons over 60 min. We measured fibrinolytic parameters serially following heparinization and demonstrated that heparin induces activation of the fibrinolytic system. We showed that the fibrinolytic system was activated in vivo as evidenced by an increase in plasmin activity and immunoreactive plasmin light chain, as well as an increase in immunoreactive fibrinogen fragment E in vitro. These results demonstrate that the fibrinolytic system is activated in vivo by the administration of heparin during cardiopulmonary bypass. These data suggest that, despite administration of a neutralizing agent such as protamine, heparin may contribute to postoperative bleeding complications following cardiopulmonary bypass surgery owing principally to its longer lived effects on the fibrinolytic system.
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PMID:Effect of heparin on fibrinolytic activity and platelet function in vivo. 877 93

Full-thickness skin ulceration after extravasation of the commonly used vesicant chemotherapeutic agent doxorubicin hydrochloride (Adriamycin) is a significant source of morbidity in cancer patients. Controversy exists regarding the appropriate management of this extravasation injury. Current therapy includes local hypothermia, local clysis with hyaluronidase, and surgical excision of the involved tissue. Experimental data supporting local clysis with hyaluronidase are limited despite its current use clinically. The purpose of this study was to determine the efficacy of local infiltration with heparin sodium, hyaluronidase, and saline in the prevention of extravasation ulcers in a rat model. One hundred fifty male Sprague-Dawley rats (Upjohn, Milan, Italy) weighing 240 to 260 g, anesthetized with sodium pentobarbital, were used in this study. One hundred thirty rats received a 0.3-ml subcutaneous flank injection of doxorubicin (1.5 mg/ml) followed 15 minutes later by local infiltration with saline (n = 10), 25 to 100 units of heparin (n = 30), or 2.5 to 10.0 units of hyaluronidase (n = 90). Control animals received either subcutaneous doxorubicin (n = 10) or subcutaneous saline alone (n = 10). Volumes of the infiltration solution were less than 1 ml in all groups. All animals were sacrificed at 4 weeks; presence and size of ulcers at the injection site were quantified. Statistical analysis was performed using the two-sided Fisher's exact test and Student's t test. Control rats injected with saline alone did not develop ulceration in any case. All rats injected with doxorubicin alone developed ulcers with an average size of 33 mm2. Heparin infiltration decreased ulcer rate by 20 to 40 percent and decreased ulcer size by up to 67 percent. Local infiltration with hyaluronidase decreased ulcer rate by 50 to 60 percent (p < 0.05, two-sided Fisher's exact test) and decreased ulcer size by up to 50 percent ( p < 0.05, Student's t test). In this rat extravasation injury model, local infiltration with saline, heparin, or hyaluronidase decreased ulcer size after doxorubicin extravasation. This effect may be secondary to dilution of the extravasant. Additionally, local infiltration with hyaluronidase decreased ulcer rate by at least 50 percent. The mechanism of this phenomenon presumably relates to the ability of hyaluronidase to temporarily decrease the viscosity of the hyaluronic acid component of ground substance, thus allowing greater diffusion of doxorubicin into the surrounding tissue and therefore decreasing its local concentration.
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PMID:Prevention of adriamycin-induced full-thickness skin loss using hyaluronidase infiltration. 946 69

Pharmacologic manipulation of hemostasis is a prerequisite for cardiac surgery with cardiopulmonary bypass (CPB) to prevent clot formation in the extracorporeal circuit. Children who require surgical correction of congenital heart defects are at increased risk for prolonged and excessive bleeding after separation from CPB. Heparin remains the anticoagulant of choice for surgery requiring CPB. Traditional regimens of empiric heparin dosing and a fixed-dose ratio of protamine to heparin for reversal of anticoagulation do not account for individual differences in the half-life of heparin, clearance of heparin, and duration of CPB, particularly in children. In addition, the use of prolongation of the activated clotting time (ACT) as a measure of adequate anticoagulation does not account for alterations in ACT by factors unrelated to heparin activity, including hemodilution and hypothermia, that are frequently present during CPB. This manuscript reviews the pitfalls in the management of anticoagulation for children undergoing surgery that requires CPB. Pertinent literature related to the use of aprotinin, a serine protease inhibitor that has been shown to improve hemostasis during and after CPB, is discussed. It is hoped that this article will provide a practical guideline for the rational management of anticoagulation in children with congenital heart disease undergoing CPB surgery.
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PMID:Monitoring and management of anticoagulation in children requiring extracorporeal circulation. 946 31

Several factors combine to facilitate the evolution towards heart and multi-organ failure following cardiac surgery. Some of these factors are related to pure cardiac aspects, for example, the existence of a preoperative heart disease, the use of aortic cross clamping or performance of cardiotomy. Cardiopulmonary bypass (CPB) also plays an important role in the occurrence of postoperative organ dysfunctions by two principal means. It induces a profound hemodilution, which impairs oxygen transport through tissues. This phenomenon becomes obvious in the postoperative period by the existence of increased transpulmonary O2 gradients, extravascular lung water volume and subsequent impairments of O2 transport. (2) Cardiopulmonary bypass is deleterious by triggering an important inflammatory reaction. This reaction is largely related to the ratio of the circuit area to the patient's body surface area and is therefore maximal in children. It has been widely demonstrated that the very early paths of this reaction imply several humoral factors including kinins, coagulation factor XII and complement fragments. The activation of these factors is self-amplified and triggers both expression and release of numerous mediators by endothelial cells and leukocytes. Finally, these mediators are responsible for the well described "post-bypass syndrome," which is, from a clinical viewpoint, very close to hyperkinetic septic shock. Several methods have been proposed to reduce the deleterious effects of both cardiac surgery and CPB. The older one is hypothermia that considerably reduces the triggering of the inflammatory mediator network. Heparin-coated circuits may also reduce this reaction to some extent. Hemofiltration has been introduced in the 1990s in CPB management. Because of its very high tolerance in patients with compromised circulatory status this technique was already used in the postoperative period to treat patients with acute renal failure. Initially hemofiltration was intended to correct the accumulation of extravascular water during or immediately following the surgical procedure. Nevertheless, several of its side-effects appeared to be useful, such as the reduction of postoperative blood loss and immediate improvement in hemodynamics. Several studies attempted to point out the mechanism of action of hemofiltration and although removal of inflammatory mediator occurs, there is currently no proof that this removal is the actual mechanism by which this technique acts.
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PMID:Hemofiltration during cardiopulmonary bypass. 957 98

Several factors combine to facilitate the evolution towards heart and multi-organ failure following cardiac surgery. Some of these factors are related to pure cardiac aspects like the existence of a preoperative heart disease, the use of aortic cross clamping or performance of cardiotomy. Cardiopulmonary bypass (CPB) also plays an important role in the occurrence of postoperative organ dysfunctions by two principal means: firstly by inducing a profound hemodilution, which impairs oxygen transport through tissues. This phenomenon is pointed out in the postoperative period by the existence of increased transpulmonary O2 gradients, extravascular lung water volume and subsequent impairments of O2 transport. Secondly CPB is deleterious by triggering an important inflammatory reaction. This reaction is largely related to the ratio of the circuit area to the patient's body surface area and is therefore maximal in children. It has been widely demonstrated that the very early paths of this reaction imply several humoral factors including kinins, coagulation factor-XII and complement fragments. The activation of these factors is self-amplified and triggers both expression and release of numerous mediators by endothelial cells and leukocytes. Finally, these mediators are responsible for the well described "post-bypass syndrome" which is, from a clinical viewpoint, very close to hyperkinetic septic shocks. Several methods have been proposed to reduce the deleterious effects of both cardiac surgery and CPB. The older one is hypothermia that considerably reduces the triggering of the inflammatory mediators network. Heparin-coated circuits may also reduce this reaction to some extent. Hemofiltration has been introduced in the 90's in CPB management. Because of its very high tolerance in patients with compromised circulatory status this technique was already used in the postoperative period to treat patients with acute renal failure. Initially hemofiltration was intended to correct the accumulation of extravascular water during or immediately following the surgical procedure. Nevertheless several of its "side-effects" appeared to be useful like reduction of postoperative blood loss and immediate hemodynamics improvement. Several studies attempted to point out the mechanism of action of hemofiltration and although removal of inflammatory mediator occurs, there is currently no proofs that this removal is the actual mechanism by which this technique acts. At the early beginning of the use of its utilization hemofiltration during cardiac surgery aimed either to concentrate blood at the end of the procedure or to rapidly restore a normal fluid and electrolytes balance. Today some new implementations of this technique are proposed either to reduce the triggering of the inflammatory reaction to CPB or to reduce the immediate postoperative drug support.
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PMID:Hemofiltration during cardiopulmonary bypass. 1039 14

Accelerated thrombin generation is central to the development of hemostatic abnormalities during cardiopulmonary bypass (CPB) that are associated with both thromboembolic complications and serious, abnormal bleeding. Thrombin not only converts fibrinogen to fibrin, but also activates platelets and coagulation factors V, VIII, and XI and causes release of von Willebrand factor from vascular endothelium. Thrombin can also downregulate the hemostatic system by inducing formation of platelet inhibitory agents, such as nitric oxide and prostacyclin, and release of tissue plasminogen activator, facilitating activation of protein C, and releasing tissue factor pathway inhibitor. Excessive thrombin activity may also result in substantial consumption of platelets, fibrinogen, and labile coagulation factors and abnormal bleeding. Elevated tissue plasminogen activator levels secondary to activation of the contact system and surgery catalyze the formation of plasmin, which also consumes or internalizes platelet glycoprotein receptors and coagulation factors V, VIII, and fibrinogen. Heparin can reduce the generation of and mediate neutralization of excessive and CPB-associated thrombin activity. Heparin anticoagulation is commonly monitored with the activated clotting time (ACT). However, the ACT may be prolonged by factors other than heparin during CPB, such as hemodilution and hypothermia, and therefore may not accurately reflect the extent of anticoagulation by heparin. Aprotinin, a nonspecific serine protease inhibitor used with CPB, can also prolong celite-based ACT values, rendering it less reliable for monitoring heparin anticoagulation. Therefore, several alternative anticoagulation strategies have been recommended when aprotinin is used, such as a higher celite ACT trigger (>750 seconds), monitoring of whole blood heparin concentrations (eg, >2.7 U/mL), or administration of heparin based on a CPB duration-dependent, fixed-dose regimen. Administration of heparin doses higher than those generally recommended, as guided by predetermined, patient-specific whole blood heparin concentration measurements during bypass, can reduce excessive thrombin-mediated consumption of platelets and coagulation factors as well as post-CPB blood loss and blood component transfusions. New modalities of improving suppression of excess thrombin generation during CPB include use of heparin-bonded CPB circuits, heparin cofactor II or related analogs, supplemental antithrombin III, direct thrombin inhibitors (eg, hirudin, argatroban), and inhibitors of the contact and tissue factor pathways. The safety and efficacy of these approaches remains to be established by additional, appropriately powered, prospective studies.
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PMID:Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update. 1046 45


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