PATHOGENESIS OF CLOSTRIDIUM-PERFRINGENS INFECTIONS - MECHANISMS AND MEDIATORS OF SHOCK

Shock, a common complication of gas gangrene caused by Clostridium per fringens, is related to the elaboration of alpha- and theta-toxins in vivo. This study compared the relative potencies of theta- and alpha-t oxins in a rabbit model and determined the role of endogenous mediator s of toxin-induced shock. alpha-Toxin decreased cardiac index, mean ar terial pressure, and heart rate and caused death in 83% of animals. th eta-Toxin did not alter these parameters and caused death in only 25% of animals. alpha-Toxin also inhibited ex vivo cardiac contractility i n a dose-dependent manner. Finally, both alpha- and theta-toxins were potent inducers of endothelial cell-derived platelet activating factor . alpha-Toxin, but not theta-toxin, also stimulated production of tumo r necrosis factor by peripheral blood mononuclear cells. Thus, the ful minant nature of shock in patients with gas gangrene caused by C. perf ringens is the sum of alpha-toxin's direct effects on myocardial contr actility and both toxins' ability to induce production of potent endog enous mediators.