Endothelium and myocardial protecting actions of taprostene, a stable prostacyclin analogue, after acute myocardial ischemia and reperfusion in cats.
The effects of taprostene, a synthetic prostacyclin analogue, were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in anesthetized cats. Taprostene (100 ng/kg/min) was infused intravenously starting 30 minutes postocclusion of the left anterior descending coronary artery followed by reperfusion 1 hour later, and the cats were observed for an additional 4.5 hours. Taprostene infusion resulted in significantly lower plasma creatine phosphokinase activities at every time from 3 to 6 hours for the MI + taprostene group compared with the MI + vehicle group and were not significantly different when compared with sham MI controls. The areas at risk, expressed as a percentage of the total left ventricular weights, were not significantly different between the MI groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the taprostene-treated cats compared with the untreated MI group (p less than 0.01). Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the area at risk and to the ischemic zone of the MI + taprostene cats when compared with the MI cats given only the vehicle. Data from isolated left anterior descending coronary artery ring preparations removed from hearts after 6 hours of ischemia indicated that the endothelium was damaged by ischemia-reperfusion injury in the untreated cats. However, endothelial dysfunction was not observed in circumflex coronary arteries of ischemic cats or in coronary rings isolated from MI + taprostene cats. Thus, taprostene exerted a significant cardioprotection in cats subjected to ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
G
G
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Furlan
L E
LE
Aoki
N
N
Lefer
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003327:Coronary Disease / Q000473:pathology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D014664:Vasodilation
D011450:Prostaglandin Endoperoxides, Synthetic; C039188:taprostene; D011464:Epoprostenol; D009195:Peroxidase; D003402:Creatine Kinase; D000109:Acetylcholine