BB-882 is a potent antagonist of the haemodynamic changes induced by platelet-activating factor in pigs.
The effects of bolus doses (0.2-2 micrograms) 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 continuous infusion of 2 mg/kg/hr, and a third dose response curve was repeated with ten-fold higher PAF doses (2-20 micrograms). BB-882 effectively counteracted these effects. Six pigs were given a continuous 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.
Abu-Zidan
F M
FM
Department of Surgery, University Hospotal, Linköping, Sweden.
Walther
S
S
Lennquist
S
S
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
C094498:BB 882; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D007930:Leucine