© 1992 by European Society of Cardiology
Copyright © 1992, European Society of Cardiology
Effect of WEB 2086 on myocardial infarct size and regional blood flow in the dog
Department of Medicine, University of Western Australia and Royal Perth Hospital, Wellington St, Perth 6000, Western Australia: L L L Leong, C J Stephens, M J Sturm
Department of Cardiology, University of Western Australia and Royal Perth Hospital, Wellington St, Perth 6000, Western Australia: R R Taylor
Correspondence to Professor Taylor.
Objective: Systemic administration of platelet activating factor (PAF, l-O-alkyl-2-acetyl-sn-glycero-phosphocholine) produces hypotension and decreased cardiac output; in isolated heart preparations PAF increases coronary vascular resistance and depresses inotropic state. A precursor of PAF bioactivity has been found early in myocardial ischaemia and other reports have suggested that PAF antagonists can reduce myocardial damage and ventricular arrhythmia. This study concerns the effects of WEB 2086, a PAF antagonist, on myocardial infarct size and coronary blood flow after total coronary artery occlusion. Methods: Open chest anaesthetised dogs (n=26) were pretreated with either WEB 2086 (5 mg·kg–1) or saline before proximal occlusion of the circumflex artery and constant infusion of WEB 2086 (1 mg·kg–1·h–1) or saline was maintained for 5 h. Cardiac output and regional myocardial flow were measured with radiolabeled microspheres (46Sc, 57Co, and 113Sn) before and immediately after occlusion and 5 h later. In the 22 dogs surviving occlusion, infarct size was determined by planimetry of cross sectional slices after exposure to triphenyltetrazolium chloride. Results: Infarct size was not different between treated and control groups, at 23.6(SEM 2.3)% v24.8(3.7)% of left ventricle, and was not different between groups when related to vasculature at risk and to collateral blood flow determined with microspheres. Conclusions: No beneficial effect of a relatively large dose of the potent PAF antagonist, WEB 2086, on myocardial infarct size or collateral blood flow was found after relatively short duration of myocardial ischaemia in the dog.
KEYWORDS platelet activating factor; myocardial infarction; microspheres
This project was supported by grants from the National Health and Medical Research Council (Australia), the Faculty of Medicine, University of Western Australia, and the Royal Perth Hospital Medical Research Foundation. We are grateful to Ms Patricia Barker and Mr Livio Mina of the department of Medical Physics, Royal Perth Hospital for their assistance and advice with the radioactive and technical aspects of this project.