Evidence for a role of platelet activating factor in the pathogenesis of irreversible but not reversible myocardial injury after reperfusion in dogs.
The role of platelet activating factor (PAF) in myocardial injury after either brief (15 minutes, stunned myocardium) or prolonged (90 minutes, infarcted myocardium) coronary artery occlusion and 3 hours of reperfusion of the left anterior descending coronary artery was investigated in barbital-anesthetized dogs. Regional myocardial blood flow was measured by radioactive microspheres, regional segment shortening by sonomicrometry, and infarct size by the triphenyltetrazolium chloride stain. Infarct size expressed as a percentage of the area at risk was significantly reduced by the intravenous administration of two structurally unrelated PAF antagonists, BN 52021 (10 mg/kg and 1 mg/kg/hr) and CV-3988 (3 mg/kg and 0.3 mg/kg/hr). Infarct size was 38% +/- 5% in the saline (control) group, (n = 7), 22% +/- 5% in the BN 52021 group (n = 7), and 19% +/- 5% in the CV-3988 group (n = 8). However, the intravenous administration of BN 52021 (5 and 10 mg/kg) and CV-3988 (5 mg/kg) had no effect on functional recovery (regional segment shortening) in the stunned myocardium after brief occlusion and reperfusion. Regional myocardial blood flow, hemodynamic data, and the incidence of cardiac arrhythmias were not significantly affected by PAF antagonists in both series of experiments at any time. These data suggest that PAF may play an important role in the pathogenesis of an evolving myocardial infarction that follows a prolonged coronary artery occlusion and reperfusion. Furthermore, PAF antagonists may have a beneficial role in reduction of the injury produced during an acute infarction. Finally, these data indicate that PAF does not appear to be an important mediator of myocardial stunning.
Maruyama
M
M
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Farber
N E
NE
Vercellotti
G M
GM
Jacob
H S
HS
Gross
G J
GJ
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004224:Diterpenes; D004285:Dogs; D004594:Electrophysiology / Q000379:methods; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C037913:CV 3988; C045856:ginkgolide B