Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation.
This study investigates the action of intravenous PGE1 on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE1 (5 micrograms/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE1 treatment. PGE1 exerted some blood-pressure-lowering activity at 5 h (P greater than 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE1 modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE1 prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE1 protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.
Schrör
K
K
Institut für Pharmakologie, Universität Düsseldorf, Federal Republic of Germany.
Thiemermann
C
C
Ney
P
P
D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D002415:Cats; D003327:Coronary Disease / Q000097:blood / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate; D007958:Leukocyte Count; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010976:Platelet Count
D009195:Peroxidase; D003402:Creatine Kinase; D000527:Alprostadil