PROSTACYCLIN RATHER THAN ENDOGENOUS NITRIC-OXIDE IS A TISSUE PROTECTIVE FACTOR IN MYOCARDIAL-ISCHEMIA

Nitric oxide (NO) and prostacyclin (PGI2) were determined in effluents of Langendorff-perfused rabbit hearts subjected to 2 h of global low-flow ischemia and subsequent reperfusion. PGI, release [6-oxo-prostaglandin (PG) F1alpha] was significantly enhanced during early reperfusion and remained elevated. NO formation was reduced during ischemia but did increase substantially during reperfusion. Indomethacin (3 muM) significantly suppressed ischemia-related 6-oxo-PGF1alpha and NO release. This was accompanied by severely diminished myocardial recovery. N(G)-nitro-L-arginine (L-NNA) (100 uM) suppressed NO generation without major effects on 6-oxo-PGF1alpha generation and cardiac dysfunction but with a remarkable increase in coronary perfusion pressure. These effects of L-NNA were antagonized by L-arginine, whereas the effects of indomethacin were not. There was a substantial loss of creatine kinase specific activity from reperfused ischemic hearts, which was further aggravated by indomethacin but not by L-NNA. These data demonstrate a cardioprotective and endothelium-protective role of PGI2 in myocardial ischemia, which also involves preservation of NO generation. Endogenous NO appears to be important for local regulation of coronary flow.