Reduction of enzyme release from reperfused ischemic hearts by steroidal and non-steroidal prostaglandin synthesis inhibitors.
Exacerbation of heart tissue damage by reperfusion of the ischemic myocardium is a well documented phenomenon. The present study was undertaken to evaluate prostaglandin (PG) involvement in reperfusion-induced damage of isolated globally ischemic rat hearts. Reperfusion produced significant increases in creatinephosphokinase (CPK) and lactic dehydrogenase (LDH) efflux which was accompanied by enhanced PG release. Three non-steroidal antiinflammatory drugs; indomethacin, mefenamic acid and ASA, and the steroidal agents; dexamethasone, hydrocortisone and methylprednisolone significantly reduced both the release of CPK and PGs upon reperfusion whereas only indomethacin and mefenamic acid decreased LDH release. There was a significant correlation between the inhibition of PG synthesis and the attenuation of CPK leakage by both non-steroidal (P less than 0.001) and steroidal (P = 0.02) antiinflammatory agents. In spite of beneficial effects on enzyme release, drug treatment did not enhance recovery of mechanical function after reperfusion. The results suggest that inhibition of PG biosynthesis may be beneficial in preserving membrane, particularly mitochondrial integrity of the reperfused myocardium.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003327:Coronary Disease / Q000201:enzymology*; D003402:Creatine Kinase / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D001241:Aspirin; D006854:Hydrocortisone; D008775:Methylprednisolone; D007213:Indomethacin