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BB-882 is a Potent Antagonist of the Haemodynamic Changes Induced by Platelet-Activating Factor in Pigs
Authors:Fikri M Abu-Zidan  Sten Walther  Sten Lennquist
Abstract:Abstract: The effects of bolus doses (0.2-2 μg) 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 seconds, 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 min. After confirming these results a novel specific PAF receptor antagonist (BB-882) was given as a 1 mg/kg bolus followed by a continous infusion of 2 mg/kg/hr, and a third dose response curve was repeated with ten-fold higher PAF doses (2-20 μg). BB-882 effectively counteracted 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 intravascular pressures. These results indicate that BB-882 is a potent PAF receptor antagonist in juvenile pigs.
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