INVOLVEMENT OF PLATELET-ACTIVATING-FACTOR (PAF) IN SEPTIC SHOCK AND PRIMING AS INDICATED BY THE EFFECT OF HETRAZEPINOIC PAF ANTAGONISTS

Pharmacological data obtained with hetrazepinoic platelet-activating factor (PAF) antagonists, such as apafant (WEB 2086) and bepafant (WEB 2170), indicate a role for PAF in septic shock and in the priming process. The effect of PAF antagonists in different models of shock states favors a role for PAF in endotoxin associated lethality, activation of inflammatory blood cells with release of mediators, cardiovascular failure and increased vascular permeability, and in the development of shock organs and organ failure. The priming process (e.g., by endotoxin or tumor necrosis factor) towards an increased susceptibility towards minute amounts of PAF has to be taken into account when considering the pathophysiological significance of PAF under in vivo conditions and in septic shock.