Calcium and phospholipase A sub 2 appear to be involved in the pathogenesis of hemorrhagic shock-induced mucosal injury and bacterial translocation

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Abstract
The mechanism by which hemorrhagic shock injures the gut and leads to the translocation of bacteria remains incompletely determined. Since increased free cellular calcium levels and phospholipase A2 activity can lead to cellular injury and both have been documented in certain shock states, the hypothesis that calcium or phospholipase A2 may play a role in hemorrhagic shock-induced gut mucosal injury and bacterial translocation was tested. Prospective animal study with concurrent controls. Small animal laboratory. Fifty-seven male Sprague-Dawley rats weighing 250 to 350 g. Five groups of rats were tested utilizing a nonlethal hemorrhagic shock model (mean arterial pressure of 30 mm Hg for 30 mins). These groups included: a) sham-shock, b) shock, c) shock plus quinacrine (inhibitor of phospholipase A2), d) shock plus diltiazem (calcium-channel blocker) administered 5 mins before hemorrhage, and e) shock plus diltiazem administered at the end of shock period and before resuscitation. At 24 hrs postshock or sham-shock, the animals were killed, the mesenteric lymph node and cecum were cultured and the gut was examined histologically. The occurrence rate of shock-induced bacterial translocation (90%) was significantly reduced in rats receiving quinacrine (27%) or preshock diltiazem (21%) (p less than .05), but not postshock diltiazem (63%). Bacterial translocation did not occur in sham-shocked rats. The same amount of blood withdrawal was needed between all groups of rats to induce and maintain shock. Quinacrine and diltiazem administration largely prevented shock-induced ileal and cecal mucosal injury. The observation that quinacrine and preshock diltiazem limited the extent of shock-induced mucosal injury and bacterial translocation indicate that calcium and phospholipase A2 are involved in the pathogenesis of shock-induced mucosal injury and bacterial translocation. The fact that preshock but not postshock diltiazem was protective indicates that the process leading to shock-induced calcium-mediated tissue injury and bacterial translocation was initiated during the ischemic rather than the reperfusion period. However, since neither quinacrine nor diltiazem was fully protective, other factors, such as oxidants, are also likely to be involved in the pathogenesis of shock-induced mucosal injury and bacterial translocation.