医学
部分凝血活酶时间
热疗
血尿素氮
蛋白质C
冲程(发动机)
凝血酶原时间
复苏
麻醉
内分泌学
内科学
血小板
肌酐
机械工程
工程类
作者
Chin‐Ming Chen,Ching-Cheng Hou,Kuo‐Chen Cheng,Ru-Ling Tian,Ching‐Ping Chang,Mao‐Tsun Lin
标识
DOI:10.1097/01.ccm.0000224231.01533.b1
摘要
To evaluate the therapeutic effects of activated protein C in an animal model of heat stroke.Laboratory investigation.Chi-Mei Medical Center research laboratory.Male Sprague-Dawley rats weighing 252-304 g.Anesthetized animals were subjected to heat stress (40 degrees C) to induce heat stroke. A bolus injection of normal saline or recombinant human activated protein C (drotrecogin alfa, activated) was conducted via femoral catheters immediately after the onset of heat stroke. Blood sampling was done before initiation of heat stress and 0 and 40 mins after the onset of heat stroke.When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 56-64 mins (n = 16). Resuscitation with activated protein C significantly and dose-dependently improved survival during heat stroke (108-246 mins for doses of 0.5-20 mg of activated protein C per kilogram of body weight) (n = 32). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor-alpha, prothrombin time, activated partial thromboplastin time, and D-dimer and decreased platelet count and protein C. Biochemical markers evidenced by cellular ischemia and injury/dysfunction included increased plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; increased striatal levels of glutamate, glycerol, and lactate/pyruvate ratio; and decreased striatal levels of partial pressure of oxygen and local cerebral blood flow, which were all observed during heat stroke. These heat stroke reactions were all significantly suppressed by resuscitation with activated protein C but not vehicle solution.The results indicate that systemic delivery of human recombinant activated protein C at the time point of onset of heat stroke may improve survival by ameliorating systemic inflammation, hypercoagulable state, and tissue ischemia and injury in multiple organs.
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