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 multip
le trauma patients up to MOF. In a manner similar to the pathophysiolo
gical sequence in multiple trauma patients, the combination of damagin
g mechanisms in the early phase (hemorrhagic shock, operating trauma,
application of endotoxin (ET; 0.75 mug/kg body weight) and zymosan-act
ivated 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 s
howed 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), arteria
l oxygen pressure declined significantly (day 1: 103.1 +/- 1.6 mmHg; d
ay 10: 89.8 +/- 4.2 mmHg). Liver function was impaired, bilirubin leve
ls 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 signific
antly in the late phase over the entire period (day 2: 104.3 +/- 26.8
ml/min; day 10: 53.1 +/- 17.6 ml/min).