EFFECTS OF FISH-OIL SUPPLEMENTATION ON THE CHANGES IN MYOCARDIAL CYCLIC ADENOSINE-MONOPHOSPHATE, INOSITOL 1,4,5-TRIPHOSPHATE AND MITOCHONDRIAL CALCIUM LEVELS DURING ACUTE CORONARY OCCLUSION-REPERFUSION IN CHOLESTEROL-FED RABBITS

We studied the changes in myocardial second messengers and mitochondrial calcium levels during acute coronary occlusion-reperfusion in New Zealand white male rabbits fed a high cholesterol diet with or without fish oil supplementation, Group I, control rabbits, were fed a standard laboratory rabbit chow. In addition to the standard chow, Group II rabbits received a 1% cholesterol-enriched diet for 2 weeks, while Group III rabbits were fed a 1% cholesterol and 10% fish oil supplemented diet for 2 weeks. Acute coronary occlusion for la min or 1 h was induced by ligating the marginal branch of the left circumflex coronary artery. The vessel was then reperfused for 1 or 4 h in short- and longterm ischemia studies respectively. In the short-term ischemia study, myocardial samples taken from the cholesterol-fed rabbits had the highest cyclic adenosine monophosphate, inositol 1,4,5-triphosphate and mitochondrial calcium levels among the normal (nonischemic) and the ischemic areas of the three groups. The cholesterol and fish oil treated rabbits significantly suppressed the elevation of cyclic adenosine monophosphate (P < 0.05 compared with the cholesterol-fed rabbits in normal and ischemic areas respectively), but did not significantly attenuate the elevation of inositol 1,4,5-triphosphate and calcium levels. In the long-term ischemia study, the cholesterol-fed rabbits had the highest levels of these three messengers among the normal areas. However, only inositol 1,4,5-triphosphate level reached statistical significance (P < 0.05 compared with control). This group of rabbits had the lowest level of cyclic adenosine monophosphate, but the highest inositol 1,4,5-triphosphate and calcium levels among the ischemic areas. Fish oil did not prevent the deterioration. These data suggest that cholesterol-fed rabbits had an adverse effect on myocardial second messengers and mitochondrial calcium levels during both short- and long-term ischemia. Fish oil supplementation in a high cholesterol diet did not attenuate this change.