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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombolysis with tissue plasminogen activator (tPA) and hypothermia are two potential treatment modalities for acute ischemic stroke. Many investigators are studying these modalities both in the laboratory and in clinical trials. Because these modalities each appear to show benefit in animal models, there is considerable interest in studying combined therapy with both thrombolysis and hypothermia. However, it is known that alterations in the coagulation system can occur with decreased body temperature. Clinicians have frequently observed bleeding problems when patients are subjected to hypothermia for a variety of reasons. Hypothermia induced coagulopathy has been attributed to a variety of factors. Hypothermia can cause platelet dysfunction, inhibition of clotting factors, increased fibrinolysis and endogenous production of a heparin-like factor. Groups who studied fibrinolysis and temperature, however, found the opposite to be the case. Clot lysis studies with streptokinase showed increased fibrinolysis at higher temperatures. Data by Mumme suggested that the peak fibrinolytic activity of streptokinase was at 40 degrees C, but at 43 degrees C fibrinolytic activity was decreased. Rijken et al studied plasminogen activation with tissue plasminogen activator (tPA), urokinase and streptokinase at extremely low temperatures. They found less plasminogen activation and fibrinogen degradation at 25 degrees C compared to 37 degrees C, but negligible differences at 10 degrees C, 0 degrees C and -8 degrees C. To our knowledge, there is no data studying the fibrinolytic activity of tissue plasminogen activator (tPA) at temperature ranges between 25-37 degrees C which is the range of temperatures used clinically for therapeutic purposes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolysis with tissue plasminogen activator (tPA) is temperature dependent. 777 62

Effect of hypothermia on cerebral infarcts was studied in rats embolized in the right carotid territory. Thirty-four served as normothermic controls receiving saline infusion only. In 16 rats hypothermia of 32 degrees C was induced by cooling with a fan, followed by embolization. The rats were kept hypothermic for the following 3 h before body temperature was raised to 37 degrees C. In 26 rats, treatment with human recombinant tissue plasminogen activator (20 mg/kg i.v. during 45 min), started 2 h after embolization. Finally, 14 rats were treated similarly with hypothermia for 3 h followed by additional rt-PA treatment starting after 2 h. Thrombolytic therapy reduced median infarct volume from 19.5% of affected hemisphere among controls to 4.6% (p = 0.006) in the treated group. Three hours of hypothermia reduced infarct volume to 1.6% (p = 0.0007). Additional rt-PA could not demonstrate further improvement in this experimental setting.
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PMID:Effect of hypothermia and delayed thrombolysis in a rat embolic stroke model. 780 45

The effect of body temperature on cerebral infarcts and thrombolytic therapy was investigated in 91 rats embolized in the right carotid territory. Hypothermia of 32 degrees C for 2 h with preembolic onset (n = 15) or hyperthermia of 39 degrees C for 2 h with postembolic onset (n = 22) was compared to normothermic controls (n = 17). After 48 h of survival, neuropathological evaluation with measurement of infarct volume was performed. Median infarct volume in percent of affected hemisphere volume was 11% (9-21, quartiles) in rats treated with hypothermia alone, compared to 46% (14-59, quartiles) in normothermic controls (P = 0.04). Hyperthermia for 2 h increased median infarct volume to 65% (37-75, quartiles). There was a positive and significant correlation between infarct volume and body temperature (R = 0.53, P = 0.0002, n = 54). Mortality rate was significantly higher among rats treated with hyperthermia compared to normothermic controls (P = 0.005). A subset of 37 rats exposed to the same temperature regimen were treated with tissue plasminogen activator (20 mg/kg i.v. during 45 min) 2 h after embolization. Judged by posttreatment carotid angiography, hyperthermic rats (n = 11) had the best degree of recanalization (P = 0.03) compared to controls (n = 17), but median infarct volume in this group was (58% (27-67, quartiles)) significantly larger (P < 0.02) than normothermic (21% (15-39, quartiles), n = 14) and hypothermic (13% (7-31, quartiles), n = 12) rats treated with thrombolytic therapy. Thrombolytic therapy following 2 h of hypothermia, could not improve the effect of hypothermia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of body temperature on infarct volume and thrombolytic therapy in a rat embolic stroke model. 806 95

The drugs used in frostbite injury care are: Plasma volume expanders (low molecular weight dextran); vasodilating agents (tolazoline hydrochloride); hypotensive agents (guanethidine monosulfate, reserpine); hemorrheologic agents (oxpentifylline); calcium blocking agents (nifedipine); sympatholytic agents (phenoxybenzamine hydrochloride); anticoagulating agents (heparin); thrombolytic enzymes (streptokinase, tissue plasminogen activator--TPA); an industrial solvent (dimethyl sulfoxide--DMSO); anti-inflammatory agents such as nonsteroidal drugs, and acetylsalicylic acid, Ibuprofen. As yet, no clear treatment policy has been determined for preventing injury secondary to the formation of oxygen free radicals, damaging neutrophils or reperfusion injury. The role of oxygen free radical scavengers and factors causing reperfusion injury is unclear at this date. Since that first reported series of 51 patients in 1960-61, 1,282 patients have been seen. Of that number, 1,026 had a diagnosis of frostbite; 151 were diagnosed as hypothermia; and 105 diagnosed as immersion injury.
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PMID:Comments on this issue of Alaska Medicine--from then (1960) until now (1993). 821 84

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.
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PMID:Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. 915 80

The lower temperatures utilized during profound hypothermic circulatory arrest (PHCA) surgery may exacerbate the hypothermia associated platelet and clotting factor dysfunction observed in conventional cardiopulmonary bypass (CPB) procedures. Hypothermia has been shown to impair the activity of the enzymes involved in the platelet activation pathways and to reduce the enzymatic activity of clotting factors upon coagulation activation. The resulting retardation of the generation of fibrin/platelet clot compounded by the presence of heparin may contribute significantly to a bleeding tendency. Excessive fibrinolytic activity may disrupt surgical wound thrombi and exacerbate haemorrhage. There is good evidence that the fibrinolytic activity, mediated predominantly by tissue plasminogen activator (tPA), is a secondary response to thrombin generated by coagulation activation, which is ongoing during CPB despite full heparinization. The effects of hypothermia on the fibrinolytic response remain to be clarified and the extent to which the lower temperatures and blood stasis associated with PHCA moderate this response is unknown. Despite impairment of coagulation activation by hypothermia there appears to be a shift in the hemostatic balance towards thrombosis presumably as a consequence of endothelial cell injury by both hypothermia and stasis induced ischemia. There is evidence that widespread microvascular thrombus deposition may occur as a consequence of stasis in patients undergoing PHCA and that this might result in vascular occlusion and end organ damage. Although it is not uncommon to find laboratory evidence of disseminated intravascular coagulation (DIC) in patients presenting with aortic aneurysm rupture or dissection, the incidence of clinically overt DIC resulting in bleeding is low. The underlying hemostatic disturbance however may contribute to the surgery-associated bleeding diathesis.
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PMID:Hematological consequences of profound hypothermic circulatory arrest and aortic dissection. 927 46

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

Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none has been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.
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PMID:Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute Ischemic Stroke. 1289 99

Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none have been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.
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PMID:Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute Ischemic Stroke. 1457 21

The last decade witnessed significant and unprecedented advances in the treatment of acute ischemic stroke. Intravenous tissue plasminogen activator and defibrinogenating agent are both now approved by the Food and Drug Administration for treatment of acute ischemic stroke within 3 h of symptom onset. Trials involving intra-arterial thrombolysis have demonstrated clinical benefit in patients treated within 6 h of symptom onset. The future for the development of new and better treatment for ischemic stroke looks very promising. Currently, induced hypothermia, laser evaporation, mechanical thrombectomy, angioplasty with stent placement, the combination of neuroprotective agents with thrombolysis, and the combination of intravenous with intra-arterial thrombolysis are being investigated.
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PMID:Acute treatment for ischemic stroke in 2004. 1530 61


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