Grotz M, Regel G, Dwenger A, Pape H C, Hainer C, Vaske R, Tscherne H
Unfallchirurgische Klinik, Medizinischen Hochschule Hannover.
Unfallchirurg. 1995 Feb;98(2):63-71.
In the past various attempts have been made to develop a standardized animal model of multiple organ failure (MOF). Until now there has been no large animal model, that imitates the clinical situation of multiple trauma patients up to MOF. In a manner similar to the pathophysiological sequence in multiple trauma patients, the combination of damaging mechanisms in the early phase (hemorrhagic shock, operating trauma, application of endotoxin (ET; 0.75 microgram/kg body weight) and zymosan-activated plasma (ZAP; 20 ml) every 12 h on days 1-5) leads to sequential irreversible damage to several organs in the late phase (> day 6) in sheep (n = 10). In this animal model representative organ parameters showed a similar course to that in MOF after multiple trauma in humans. The cardiac index increased significantly in the late phase (day 1: 6.47 +/- 0.41 ml/min x m2; day 10: 10.36 +/- 0.79 ml/min x m2), arterial oxygen pressure declined significantly (day 1: 103.1 +/- 1.6 mmHg; day 10: 89.8 +/- 4.2 mmHg). Liver function was impaired, bilirubin levels showed a significant increase (day 1: 2.94 +/- 0.34 mumol/l; day 10: 7.19 +/- 0.91 mumol/l). Creatinine clearance was low on day 1 (54.3 +/- 7.4 ml/min), increased up to day 5 and deteriorated again significantly in the late phase over the entire period (day 2: 104.3 +/- 26.8 ml/min; day 10: 53.1 +/- 17.6 ml/min).
过去曾多次尝试开发多器官功能衰竭(MOF)的标准化动物模型。到目前为止,还没有一种大型动物模型能够模拟多发伤患者直至MOF的临床情况。以类似于多发伤患者病理生理过程的方式,在第1 - 5天,早期损伤机制(失血性休克、手术创伤、内毒素(ET;0.75微克/千克体重)和酵母聚糖激活血浆(ZAP;20毫升)每12小时一次)的组合导致绵羊(n = 10)在后期(>第6天)多个器官出现相继不可逆损伤。在这个动物模型中,代表性器官参数显示出与人类多发伤后MOF相似的变化过程。心脏指数在后期显著增加(第1天:6.47±0.41毫升/分钟×平方米;第10天:10.36±0.79毫升/分钟×平方米),动脉血氧分压显著下降(第1天:103.1±1.6毫米汞柱;第10天:89.8±4.2毫米汞柱)。肝功能受损,胆红素水平显著升高(第1天:2.94±0.34微摩尔/升;第10天:7.19±0.91微摩尔/升)。第1天肌酐清除率较低(54.3±7.4毫升/分钟),到第5天升高,在整个后期又再次显著恶化(第2天:104.3±26.8毫升/分钟;第10天:53.1±17.6毫升/分钟)。