Reduction of experimental canine myocardial infarct size with prostaglandin E1: inhibition of neutrophil migration and activation.
The ability of prostaglandin E1 (PGE1) to reduce myocardial infarct size in an anesthetized open-chest canine model of regional myocardial ischemia and reperfusion was investigated. Administration of PGE1 (100 ng/kg/min into the left atrium) to dogs beginning 10 min after left circumflex coronary artery (LCCA) occlusion and continuing up to 2 hr of reperfusion resulted in a 43% reduction in infarct size expressed as a percentage of the area at risk: control infarct, 44.3 +/- 3.2%, n = 15; PGE1, 27.3 +/- 3.2%, n = 19, P less than .0005. Regional myocardial blood flow (measured with tracer-labeled microspheres in six dogs from each group) was similar between treatment groups at base line, 5 min after LCCA occlusion, 80 min after LCCA occlusion and 1 hr after LCCA reperfusion. In another group of anesthetized dogs, PGE1 was tested for its ability to decrease neutrophil migration into skin lesions. PGE1 at the same concentration that reduced infarct size, decreased the number of neutrophils (assessed by myeloperoxidase activity) that accumulated in skin lesions after intradermal injection of C5a by 63%. In addition, PGE1 inhibited the production of superoxide anion in vitro by zymosan-stimulated canine neutrophils in a concentration-dependent manner. Thus, PGE1 reduces myocardial infarct size and inhibits neutrophil function in vitro and in vivo. These data suggest that the reduction in infarct size by PGE1 may be due to multiple mechanisms including: 1) inhibition of neutrophil migration and activation at the site of tissue injury or 2) reduction in blood pressure which reduces myocardial oxygen demand.
Simpson
P J
PJ
Department of Pharmacology University of Michigan Medical School, Ann Arbor.
Mickelson
J
J
Fantone
J C
JC
Gallagher
K P
KP
Lucchesi
B R
BR
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis; D013481:Superoxides / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000517:prevention & control
D013481:Superoxides; D009195:Peroxidase; D000527:Alprostadil