Modulation of lung injury by platelet-activating factor antagonism in nonhypotensive porcine endotoxemia.

Abstract

Endotoxemia was induced by intravenous infusion of Escherichia coli endotoxin in 18 anesthetized pigs in a dose of 36 micrograms/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 pigs received a similar volume of vehicle. Normotension was maintained with intravenous crystalloid resuscitation. Six pigs received only BB-882 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 resistance, which was significantly attenuated by BB-882 (P < 0.01, repeated measurements ANOVA). Endotoxin-induced arterial deoxygenation and fall in lung/thorax compliance was not significantly altered by BB-882. 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.