MODULATION OF LUNG INJURY BY PLATELET-ACTIVATING-FACTOR ANTAGONISM INNONHYPOTENSIVE PORCINE ENDOTOXEMIA

Endotoxemia was induced by intravenous infusion of Escherichia coil en dotoxin in 18 anesthetized pigs in a dose of 36 mu g/kg/hr. Nine pigs were pretreated with BB-882, a novel platelet-activating factor (PAF) antagonist, 33 mg/kg/hr, starting 30 min before endotoxin, and nine pi gs received a similar volume of vehicle. Normotension was maintained w ith intravenous crystalloid resuscitation. Six pigs received only BB-8 82 and served as controls. Endotoxemia induced an acute transient 300% increase in pulmonary vascular resistance, identical in both groups. The initial increase was followed by a second, more gradual, rise in r esistance, which was significantly attenuated by BB-882 (P < 0.01, rep eated measurements ANOVA). Endotoxin-induced arterial deoxygenation an d fall in lung/thorax compliance was not significantly altered by BB-8 82. Hematocrit was less in endotoxic pigs receiving BB-882 (P < 0.02). There were no significant changes compared to baseline in the control group. The results indicate that PAF is a minor determinant of early pulmonary dysfunction in nonhypotensive porcine endotoxemia. (c) 1995 Wiley-Liss, Inc.