Myocardial ischemia is associated with accumulation of lyso-
phospholipids, including
lyso-platelet activating factor, the degradation product and precursor of
platelet activating factor. These compounds produce cellular and microvascular damage and, in the myocardium, depression of contractility and
arrhythmia. The potent
platelet activating factor antagonist,
WEB 2086, or placebo, was infused (IV) 10 min before constriction of the proximal left anterior descending coronary artery in open-chest dogs. Two protocols were followed: the dose of
WEB 2086 was 0.5 mg/kg in those subjected to 20 min
ischemia with 10 min reperfusion (n = 40) and 5 mg/kg preceding 60 min
ischemia alone (n = 24). There was no significant difference in the number of
ventricular premature complexes between
WEB 2086 and placebo treated dogs during either period of
ischemia. On reperfusion in those surviving 20 min of
ischemia, 5 of the 18
WEB 2086 and 9 of the 18 placebo treated dogs developed
ventricular fibrillation (NS). After 60 min of
myocardial ischemia, there was no statistical difference in histological changes (nuclear swelling, aggregation of
chromatin, myofibrillar separation) between groups. Hence, no substantial effect of relatively large doses of
WEB 2086 on
ischemia-induced histological change or
arrhythmia was found in this preparation.