ON THE COLLAPSE OF BACTERIAL ENDOTOXIN RESISTANCE FOLLOWING HEMORRHAGE

Unanesthetized immature albino rabbits exposed to 2 hours of severe but reversible hemorrhagic shock induced with aseptic precautions by multiple cardiac bleedings exhibited no increase in susceptibility to single intravenous injections of 200 µg./kg. E. coli endotoxin administered 4 hours post retransfusion, a quantity of endotoxin that was found to be the largest dose uniformly non-lethal to normal rabbits. Paired and randomly selected rabbits treated identically except for the additional procedure of a femoral arterial cutdown and ligation (without aseptic precautions) exhibited increases in susceptibility to the same endotoxin of several hundredfold. This effect could not be attributed to the femoral cutdown and arterial ligation alone since such trauma when coupled with sham cardiac bleedings failed to increase susceptibility to 200 µg./kg. of endotoxin. These data appear valid since sham cardiac bleedings produced no detectable impairment of myocardial contractility, while 2 hours of hemorrhagic shock at 50 mm. Hg with the Lamson reservoir technique caused an increase in endotoxin susceptibility comparable to that seen when cardiac bleedings were combined with a non-sterile femoral arterial cutdown and ligation. The mechanisms increasing the susceptibility to E. coli endotoxin were investigated. It was found that (a) rabbit femoral skeletal muscle is normally contaminated with clostridia, (b) the use of aseptic femoral wounding precautions exerted some suggestive protective influence, (c) the use of aseptic wounding precautions combined with immediate topical sulfanilamide and wound closure exerted a significant protective influence, and (d) prophylactic polyvalent gas gangrene antitoxin protected in a manner not demonstrable when diphtheria antitoxin was employed as a control. These observations suggest that clostridial wound infection is one mechanism whereby a femoral arterial cutdown lowers endotoxin resistance of the rabbit following hemorrhagic shock. It is, however, not the only mechanism since the ligation of a femoral artery during hemorrhagic shock led to edema following retransfusion equivalent to a mean of approximately 30 per cent of the original circulating plasma volume. The intensification of shock caused by this transudation presumably intensified reticulo-endothelial injury, and thus further lowered the resistance of the rabbit to an intravenous injection of endotoxin 4 hours following retransfusion.