The effects of a PAF antagonist on ischemic myocardial damage and arrhythmia in the dog.
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.
Leong
L L
LL
Department of Medicine, University of Western Australia, Perth.
Sturm
M J
MJ
Papadimitriou
J M
JM
Stephens
C J
CJ
Taylor
R R
RR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D003327:Coronary Disease / Q000517:prevention & control*; D004285:Dogs; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013610:Tachycardia / Q000517:prevention & control; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000517:prevention & control
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086