Bouchama A, Roberts G, Al Mohanna F, El-Sayed R, Lach B, Chollet-Martin S, Ollivier V, Al Baradei R, Loualich A, Nakeeb S, Eldali A, de Prost D
Dept. of Comparative Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
J Appl Physiol (1985). 2005 Feb;98(2):697-705. doi: 10.1152/japplphysiol.00461.2004. Epub 2004 Oct 8.
The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory and hemostatic responses to heat stress, suggesting that immunomodulation may improve outcome. We postulated that an experimental baboon model of heatstroke will reproduce human responses and clinical outcome to allow testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio hamadryas) were subjected to heat stress in an incubator maintained at 44-47 degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0 and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic inflammation and activated coagulation, indicated by increased plasma IL-6, prothrombin time, activated partial thromboplastin time, and D-dimer levels, and decreased platelet count. Biochemical markers and/or histology evidenced cellular injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase, lactic dehydrogenase, and alanine aminotransferase were increased, and varying degrees of tissue damage were present in liver, brain, and gut. No baboon with severe heatstroke survived. Neurological morbidity but no mortality was observed in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater coagulopathy, inflammatory activity, and tissue injury than survivors. Sham-heated animals had an uneventful course. Heat stress elicited distinct patterns of inflammatory and hemostatic responses associated with outcome. The baboon model of heatstroke appears suitable for testing whether immunomodulation of the host's responses can improve outcome.
中暑的死亡率和神经功能障碍被认为与宿主对热应激的炎症和止血反应有关，这表明免疫调节可能改善预后。我们推测，中暑的实验性狒狒模型将重现人类的反应和临床结局，以便测试新的治疗策略。八只麻醉的幼年狒狒（阿拉伯狒狒）在保持于44-47摄氏度的培养箱中接受热应激，直到直肠温度达到42.5摄氏度（中度中暑；n = 4）或收缩压降至<90 mmHg（重度中暑；n = 4），然后在室温下恢复。四只假加热的动物作为对照组。热应激结束时的直肠温度分别为42.5±0.0和43.3±0.1摄氏度。所有热应激动物均出现全身炎症和凝血激活，表现为血浆IL-6、凝血酶原时间、活化部分凝血活酶时间和D-二聚体水平升高，血小板计数降低。生化标志物和/或组织学证据显示细胞损伤/功能障碍：血浆血栓调节蛋白、肌酐、肌酸激酶、乳酸脱氢酶和丙氨酸转氨酶水平升高，肝脏、大脑和肠道存在不同程度的组织损伤。重度中暑的狒狒无一存活。中度中暑的狒狒出现神经功能障碍但无死亡。非存活者的凝血障碍、炎症活动和组织损伤明显大于存活者。假加热的动物病程平稳。热应激引发了与结局相关的不同炎症和止血反应模式。中暑的狒狒模型似乎适合测试对宿主反应进行免疫调节是否能改善结局。
