Effects of nicorandil on coronary circulation and myocardial ischemia

Abstract

The effect of the new antianginal drug, nicorandil, was studied in several models of myocardial ischemia in anesthetized dogs. In animals subjected to an acute or chronic coronary artery occlusion, nicorandil produced increases in collateral perfusion when changes in aortic pressure were minimized. In a model of irreversible ischemia, nicorandil produced a marked (50%) decrease in myocardial infarct size. In several models of reversible ischemiareperfusion injury, the “stunned myocardium,” nicorandil was shown to enhance the recovery of systolic segment shortening after a brief period (15 to 30 minutes) of coronary occlusion. Other vasodilators such as nitroglycerin or nifedipine were not as efficacious as nicorandil. In a model of multiple (n = 3) coronary occlusion (5 minutes) with intermittent (30 minutes) reperfusion, nicorandil improved the recovery of systolic segment shortening during reperfusion and prevented the loss of adenosine triphosphate and tissue edema that occurred in untreated hearts. The beneficial effects of nicorandil on functional and metabolic recovery after recurrent ischemia was shown to be partially the result of an energy-sparing effect of nicorandil to reduce free fatty acid use during the ischemic period. Cyclooxygenase blockade with indomethacin did not block the beneficial effects of nicorandil in the stunned myocardium. These results suggest that nicorandil does not promote an increase of prostacyclin. Finally, nicorandil was found to inhibit superoxide anion production by human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine plus cytochalasin B. These results suggest that part of the beneficial actions of nicorandil may occur during reperfusion and may be the result of a reduction in oxygen free radical production. Thus, nicorandil has been found to be a highly efficacious agent in reducing ischemia and reperfusion injury in a number of animal models by several mechanisms.