Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion

The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 an d 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy m etabolism under normoxic conditions and during postischemic reperfusion. Th e animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO ); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Prono va) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decrea sed n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steat osis (HS) characterized by the whitish appearance of the liver. It also bro ught about marked changes in the fatty acid composition of plasma and mitoc hondrial phospholipids. These changes, characterized by the impairment of D elta5- and Delta6-desaturases, were more obvious in the SSO-fed rats, proba bly because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed r ats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, witho ut modification of the proportion of 20:4 n-6. In the mitochondrial phospho lipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). C ardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k(012) representing the activity of the adenyla te kinase varied in the opposite direction, suggesting that decreased ADP c oncentrations could cause oxygen wasting through the opening of the permeab ility transition pore. The recovery of the pump function tended to be incre ased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of asco rbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This support s greater ischemia/reperfusion-induced calcium accumulation in the SSO grou ps than in the FO groups. HS did not modify the mitochondrial energy metabo lism during ischemia/reperfusion. Taken together, these data suggest that H S- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during post-ischemic reperfus ion.