BB-882 IS A POTENT ANTAGONIST OF THE HEMODYNAMIC-CHANGES INDUCED BY PLATELET-ACTIVATING-FACTOR IN PIGS

The effects of bolus doses (0.2-2 mu g) of platelet-activating factor (PAF) on systemic and pulmonary arterial pressures were tested in five juvenile pigs, and were demonstrated to have a biphasic effect. There was an initial drop in the mean systemic arterial pressure within sec onds, followed by an increase within 1-2 min., whereas mean pulmonary arterial pressure only rose. The response was dose-related and did not include tachyphylaxis. The pressures returned to baseline within 10 m in. After confirming these results a novel specific PAF receptor antag onist (BB-882) was given as a 1 mg/kg bolus followed by a continous in fusion of 2. mg/kg/hr, and a third dose response curve was repeated wi th ten-fold higher PAF doses (2-20 mu g). BB-882 effectively counterac ted these effects. Six pigs were given a continous infusion of BB-882 33 mg/kg/hr for 5 hr and were compared with another group of five pigs given vehicle only. In this high dose BB-882 did not affect the intra vascular pressures. These results indicate that BB-882 is a potent PAF receptor antagonist in juvenile pigs.