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)

In a pilot-study (n = 66) and subsequent controlled experiment (n = 32) the ischemic tolerance of dog liver is examined by means of various clinical and laboratory parameters. During normothermia and without venous decompression the time of ischemic tolerance amounts to 60 minutes. Hypothermia and systemic administration of Aprotinin (Trasylol) and Methylprednisolone (Urbason) do not prolong the tolerance time of ischemia. This time is significantly extended by pre-operative administration of a thiourea-derivate (Propycil). Basing on this decisive improvement of the ischemic tolerance of dog liver, new advances in increasing the ischemic tolerance of human liver are offered.
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PMID:[Efficacy of various treatment methods to extend the ischemia tolerance time of the liver. Experimental studies in dogs]. 170 Aug 71

Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion-transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly
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PMID:Bleeding complications associated with cardiopulmonary bypass. 222 18

Protective action of aprotinin froom ischemic myocardial damage was evaluated in 9 patients compared to non-treated 18 patients, who underwent open heart surgery (22 ACB, 3 AVR and 2 MVR) with respect to the alterations of beta-glucronidase, acid-phosphatase, MB-CPK and m-GOT. Cold cardioplegia with glucose-insulin-potassium solution was used in this investigation. Average arrest time was 78.6 +/- 4.9 minutes associated with hypothermia between 25 and 28 degrees C in rectal temperature. Aprotinin was administered in 9 patients intravenously with 5,000 KIU/Kg 30 minutes prior to CPB and then 5,000 KIU/Kg in the prime solution. Activity of beta-glucronidase was significantly suppressed in the aprotinin-treated group compared to the non-treated group following cardioplegia and in the reperfusion period up to 6 hours, however, acid-phosphatase failed to demonstrate significant difference among two groups. Serum MB-CPK and m-GOT levels in the aprotinin-treated group did not elevate the beginning of reperfusion following cardioplegia. These data suggest that aprotinin add myocardial protection to cold cardioplegia.
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PMID:Additive protection of aprotinin, protease inhibitor to cold cardioplegia from ischemic myocarium. 615 91

Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety and efficacy during profound hypothermia and circulatory arrest have been questioned, however. A retrospective review compared 24 patients who received aprotinin during complex aortic procedures under profound hypothermia and circulatory arrest with 24 age-matched patients undergoing similar procedures without aprotinin. Activated clotting time was maintained at longer than 500 seconds (kaolin activating agent) or longer than 750 seconds (celite). We observed no statistically significant difference in the incidence of neurologic events (p not significant) or myocardial infarctions (p not significant), and there was a trend toward reduced in-hospital mortality rate in aprotinin-treated patients. A higher incidence of postoperative renal dysfunction was encountered in aprotinin-treated patients. Aprotinin recipients had a significant reduction in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude that aprotinin may be safely and effectively used in patients undergoing deep hypothermia and circulatory arrest.
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PMID:Safety and efficacy of aprotinin under conditions of deep hypothermia and circulatory arrest. 852 71

Bleeding remains a complication of certain complex surgical procedures, particularly those cardiac operations associated with long bypass times and profound hypothermia. Clinical and novel experimental strategies to reduce bleeding and the need for blood and blood-product transfusions are the focus of this review. Preoperative assessment of the patient will identify drug-induced, acquired, or inherited coagulation defects that may contribute to this problem. The main attention is directed to the perioperative period, and broad areas discussed include the preoperative use of erythropoietin to increase red blood cell mass, autologous donation either preoperatively or before bypass, autotransfusion/hemofiltration, and acceptance of relative anemia both during the operation and into the postoperative period. A further, often overlooked, management strategy in treating major coagulopathies is the consideration of the cost and half-lives of the coagulation factors in individual blood components. Prevention of bleeding has become possible both by manipulation of the control of coagulation and inflammatory processes and by the introduction of pharmacologic agents such as aprotinin. Aprotinin is widely used and has proven efficacy in the management of excess bleeding. It is a serine protease inhibitor and has several possible mechanisms of action, including inhibition of the plasma enzyme systems activated by contact with the foreign surface of the bypass circuit and preservation of platelet function. Safety issues include the possibility of hypersensitivity and anaphylactic reaction on a second exposure. Concerns that aprotinin may induce a prothrombotic or coagulant state have no basis in theory or any good evidence in the current literature. A recent study specifically sought to identify the presence of disseminated microvascular platelet-fibrin thrombi present at autopsy in patients who had received aprotinin therapy. The study concluded that diffuse platelet-fibrin thrombi were not a direct complication of aprotinin therapy. Finally, modern molecular biology has led to the recent development of an inhibitor for factor IXa that competitively replaced IXa in the intrinsic complex and blocked the conversion of factor X to factor Xa. This compound is under investigation in animal studies. These have so far shown efficacy in reducing blood loss after bypass in comparison with standard heparin anticoagulation.
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PMID:Management of bleeding complications in redo cardiac operations. 956 96

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

Postoperative morbidity after coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) can be influenced by pro- and anti-inflammatory cytokines like interleukin 6 (IL-6) and IL-10 triggering and balancing the acute phase response. The extent of cytokine release can be modulated by different methods. This prospective randomized study examines the effect of treatment of patients with steroid (group 1, 250 mg of prednisolone)(Solu-Decortin H)), aprotinin (group 2, 6 Mio. KIU [kallikrein inhibitory units] aprotinin [Trasylol]), and heparine coating of the artificial surface (group 3, Bioline) on the systemic release of IL-6 and IL-10 in four groups of 40 patients with coronary artery disease (CAD) scheduled for CABG. Group 4 (standard medication) served as control. Twenty hemodynamic and biochemical parameters of the CPB were analyzed regarding correlation to cytokine levels measured by enzyme-linked immunosorbent assay (ELISA). In group 1, IL-6 was suppressed compared to the control (P< 0.01). IL-10 was upregulated (P< 0.01). In group 2, cytokine release was similar to group 1. Using heparin-coated circuits in group 3 led to IL-10 upregulation (P < 0.05) and IL-6 suppression (P < 0.05). We found an exponential relationship between IL-10 levels (IL-6 levels) and cardiac ischemia time, duration of CPB, and the extent of negative base excess. An inverse relationship was found for IL-10 (IL-6) levels and venous O2 saturation (SvO2), and mean arterial pressure (MAP). Hypothermia (<34 degrees C) reduced IL-10 and IL-6 release, whereas long duration of hypothermia correlated with higher IL-10 and IL-6 release. Cytokine release after extracorporeal circulation (ECC) can be modulated pharmacologically and by distinct perfusion regimen.
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PMID:Modulating IL-6 and IL-10 levels by pharmacologic strategies and the impact of different extracorporeal circulation parameters during cardiac surgery. 1177 31