The effects of PAF antagonists on arrhythmias and platelets during acute myocardial ischaemia and reperfusion.
The aim of the study was to examine a possible role for platelet activating factor (PAF) in experimental myocardial ischaemia and reperfusion. Anaesthetized open-chest greyhounds were subjected to 40 min of coronary artery (LAD) occlusion followed by reperfusion. Blood samples for platelet counting were obtained from a local coronary vein draining the ischaemic region. Pretreatment with PAF antagonists BN52021 (5 mg kg-1 i.v.) or SRI63441 (10 mg kg-1 i.v.), 15 min prior to occlusion reduced the ventricular ectopic count during the ischaemic period from 614 +/- 82 (controls) to 296 +/- 145 (BN52021) and 474 +/- 200 (SRI63441). Both drugs also reduced the incidence of ventricular fibrillation (VF) (during ischaemia and reperfusion) from 90% (controls), to 50% (BN52021) and 43% (SRI63441). Ischaemia was accompanied by a 32 +/- 7% reduction in coronary venous platelets; this was attenuated by both BN52021 (-2 +/- 6%) and SRI63441) (-1 +/- 5%). These results suggest that PAF may contribute to ischaemia and reperfusion-induced arrhythmias by activating platelets.
Wainwright
C L
CL
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, U.K.
Parratt
J R
JR
Bigaud
M
M
D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D005117:Cardiac Complexes, Premature / Q000188:drug therapy*; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004224:Diterpenes; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D046934:Ginkgolides; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D010100:Oxygen / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010976:Platelet Count / Q000187:drug effects; D011806:Quinolinium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013610:Tachycardia / Q000188:drug therapy*; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000517:prevention & control
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; C050531:SRI 63-441; C045856:ginkgolide B; D010100:Oxygen