Hinshaw L B, Benjamin B, Archer L T, Beller B, Coalson J J, Hirsch J G
Surg Gynecol Obstet. 1976 Jun;142(6):893-900.
The present study was designed to develop an animal model applicable to the clinical patient in the investigation of the pathogenesis of septic shock. The model currently described is a lightly anesthetized, unrestrained monkey, carefully monitored during a 24 hour observation period. Varying doses of live Excherichia coli organisms were infused intravenously during a 30 minute period, and a variety of hemodynamic, respiratory and metabolic parameters were monitored. Doses of organisms varied between 7.6X10(9) and 3.0X10(11) organisms per kilogram of body weight, and there was no obvious correlation between size of dose and survival time. Two of nine experimental monkeys survived the Excherichia coli, while times of death of the remaining monkeys varied between three and 27 hours. Two control monkeys, not administered organisms, survived the 24 hour period with minimal changes in all measured parameters. Results reveal two patterns in response to organism administration. These were early acute death, after three to four hours, and prolonged life, death after 20 to 27 hours. The acute response was characterized by marked systemic hypotension, hypoglycemia, hypoinsulinemia, increased lactate level, decreased pH or respiratory depression. The other type of response involved profound sustained hypotension with hypoglycemia and hypoinsulinemia in most monkeys and elevations in lactate, blood urea nitrogen potassium creatinine, serum glutamicoxalacetic, lactic dehydrogenase and fractionatedlactic dehydrogenase levels. Depressions in respiration were not evident in the group which survived a longer period of time. Renal fibrin thrombi, prominent in baboons administered Escherichia coli, were absent in the rhesus monkey regardless of the size of the dose of organisms. The results of this study suggest the operation of a multifactiorial mechanism in septic shock with interactions between hemodynamic and metabolic factors varying within the species.
本研究旨在建立一种适用于临床患者的动物模型，用于脓毒症休克发病机制的研究。目前所描述的模型是一只轻度麻醉、未加束缚的猴子，在24小时观察期内进行仔细监测。在30分钟内静脉注射不同剂量的活大肠杆菌，同时监测各种血流动力学、呼吸和代谢参数。每公斤体重注射的细菌剂量在7.6×10⁹至3.0×10¹¹个细菌之间，剂量大小与存活时间之间无明显相关性。9只实验猴子中有2只在注射大肠杆菌后存活，其余猴子的死亡时间在3至27小时之间。2只未注射细菌的对照猴子在24小时观察期内存活，所有测量参数仅有微小变化。结果显示，对细菌注射有两种反应模式。一种是早期急性死亡，发生在3至4小时后；另一种是存活时间延长，在20至27小时后死亡。急性反应的特征是明显的全身性低血压、低血糖、低胰岛素血症、乳酸水平升高、pH值降低或呼吸抑制。另一种反应类型则是大多数猴子出现深度持续性低血压，并伴有低血糖和低胰岛素血症，同时乳酸、血尿素氮、钾、肌酐、血清谷草转氨酶、乳酸脱氢酶及同工酶水平升高。在存活时间较长的一组中，呼吸抑制不明显。在注射大肠杆菌的狒狒中明显出现的肾纤维蛋白血栓，在恒河猴中无论注射细菌剂量大小均未出现。本研究结果提示，脓毒症休克存在多因素机制，血流动力学和代谢因素之间的相互作用在不同物种间有所不同。
