Effect of WEB 2086 on myocardial infarct size and regional blood flow in the dog.
OBJECTIVE
Systemic administration of platelet activating factor (PAF, 1-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 radiolabelled 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)% v 24.8(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.
Leong
L L
LL
University of Western Australia, Royal Perth Hospital.
Stephens
C J
CJ
Sturm
M J
MJ
Taylor
R R
RR
D000818:Animals; D001381:Azepines / Q000032:analysis / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications*; D004195:Disease Models, Animal; D004285:Dogs; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects; D014230:Triazoles / Q000032:analysis / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086