EFFECTS OF DIETARY SUPPLEMENTATION WITH FISH OIL ON PROSTANOID METABOLISM DURING ACUTE CORONARY-OCCLUSION WITH OR WITHOUT REPERFUSION IN DIET-INDUCED HYPERCHOLESTEROLEMIC RABBITS

We studied the changes in myocardial and aortic concentrations of prostacyclin and thromboxane A2 during acute coronary occlusion with or without reperfusion in rabbits fed with a cholesterol-enriched diet with or without fish oil supplementation for a short (5 days) or long period (6 weeks). New Zealand white male rabbits were divided into 5 groups: Group I, 15 control rabbits fed with a laboratory standard rabbit chow. In addition to the standard chow, the 4 study groups were treated with cholesterol or fish oil. Group II, 17 rabbits fed with a 1% high cholesterol diet for 5 days, Group III, 16 rabbits fed with a diet containing 1% cholesterol and 10% fish oil for 5 days. Group IV, 17 rabbits fed with the same diet as group II for 6 weeks. Group V, 18 rabbits fed with the same diet as group III for 6 weeks. Each group of rabbits was randomly divided into the coronary occlusion or occlusion-reperfusion mode of experiment. Acute coronary occlusion was induced by ligating the marginal branch of the left circumflex coronary artery for 1 h. Subsequent reperfusion for 4 h was performed in the occlusion-reperfusion rabbits. The aortic tissue above the aortic valve and the ischemic and normal (nonischemic) areas of the left ventricle were excised for the measurement of 6-keto-PGF1-alpha and thromboxane B2 levels by radioimmunoassay. Both during coronary occlusion and occlusion-reperfusion, rabbits showed higher myocardial concentrations of 6-keto-PGF1-alpha and thromboxane B2 in the ischemic area than in the normal myocardium. The differences in myocardial levels of these two prostanoids between the ischemic and normal areas were higher in the occlusion-reperfusion model as compared to occlusion alone. The cholesterol-fed rabbits treated for either 5 days or 6 weeks showed larger myocardial differences in concentrations of these two prostanoids than the corresponding groups of rabbits fed also with fish oil. In terms of 6-keto-PGF1-alpha/thromboxane B2 ratios, the 5-day cholesterol and fish oil treated rabbits had the highest ratios among the 5 groups in the normal and ischemic myocardia of the occlusion study, but not in the ischemic area of the occlusion-reperfusion study. This trend was also found in the rabbits fed with the same diet for 6 weeks. The 6-keto-PGF1-alpha/thromboxane B2 ratio of the aortic tissue showed the same pattern as that of the left ventricle. The control rabbits had a higher myocardial 6-keto-PGF1-alpha/thromboxane B2 ratio than the 5-day or 6-week cholesterol-fed rabbits in the ischemic area of the coronary occlusion study. In conclusion, rabbits fed a high cholesterol diet showed a possibly harmful pattern of prostanoid metabolism. Fish oil supplementation together with a high cholesterol diet improved the prostanoid balance in the ischemic myocardium during acute coronary occlusion but not in the occlusion-reperfusion study.