DELAYED TREATMENT WITH PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONISTWEB-2086 ATTENUATES PULMONARY DYSFUNCTION IN PORCINE ENDOTOXIN-SHOCK

The triazolodiazepine WEB 2086, a specific platelet activating factor (PAF) receptor antagonist, has previously been shown to prevent pulmon ary hypertension, hypoxia, and bronchoconstriction when given before b acterial lipopolysaccharide (LPS). The aim of the present study was to examine whether WEB 2086 reduced these changes even when given after the onset of LPS-induced shock. In a randomized trial LPS was given in travenously (IV) in a dose of 1 mu g/kg/h for 8 hours to anesthetized, ventilated pigs. Ten animals received LPS and WEB 2086, 10 mg/kg/h IV for 6.5 hours, beginning 1.5 hours after LPS. Ten control animals rec eived LPS and saline. During treatment with WEB 2086, pulmonary hypert ension was significantly attenuated compared with the findings in the control group. Gas exchange, airway pressure, extravascular lung water levels, intrapulmonary shunt, and cathepsin 8 levels in plasma showed a trend toward improvement but the group differences were not statist ically significant. These data indicate that the PAF antagonist WEB 20 86 can partially block pulmonary dysfunction and enzyme release from i nflammatory cells when given during ongoing LPS shock in pigs, and tha t PAF may be an important mediator of the cardiopulmonary changes seen in septic shock.