title: Influence of the phospholipid n-6/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia.
abstract: The influence of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on heart pump function and mitochondrial energy metabolism was investigated before and after ischemia. Weanling male Wistar rats were fed for 8 weeks a diet containing either 10% of sunflower seed oil (SSO group) or 10% of a 1:1 (w/w) mixture of fish oil and sunflower seed oil (FO group). The hearts were perfused according to the working mode for 15 min with a Krebs-Henseleit medium containing glucose (11 mM), insulin (10 IU/L) and caprylic acid (25 microM). They were then either maintained in normoxic conditions (70 min) or subjected to a global no-flow normothermic ischemia (20 min) followed by reperfusion (50 min). The aortic and coronary flows were monitored at 5-min intervals. The lactate dehydrogenase (LDH) release in the coronary effluent was evaluated in the control hearts and during ischemia/reperfusion. At the end of the perfusion, two subpopulations of mitochondria were prepared from each heart, by either mechanical or enzyme extraction (ME and EE mitochondria, respectively). The succinate dehydrogenase (SDH) activity was evaluated. Furthermore, the respiration parameters were assessed with either glutamate (20 mM) or palmitoylcarnitine (25 microM) as substrate. Substituting sunflower seed oil by fish oil in the diet provoked a large decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. The n-3 PUFA enrichment did not alter the coronary and aortic flows nor the LDH release in physiological conditions. Conversely, during post-ischemic reperfusion, the increased amount of n-3 PUFA improved the recovery of aortic flow and decreased the LDH release, without affecting significantly the coronary flow. In ME and EE mitochondria, the phospholipid n-6/n-3 PUFA ratio was similarly modified by the dietary manipulations. The analysis of total cardiac SDH activity suggested an ischemia-induced oedema, of similar magnitude in the two dietary groups. However, neither dietary manipulations nor ischemia influenced the mitochondrial extraction. Similarly, the parameters of glutamate oxidation were also unaffected. Conversely, with palmitoylcarnitine, post-ischemic reperfusion induced a decrease in both state III respiration rate and energy production which were more important in the EE mitochondria of the SSO group. These results suggest that the recovery of mitochondrial energy metabolism and myocardial pump function during reperfusion may be improved in n-3 PUFA-rich hearts. This could be related to a lower injury in n-3 PUFA-rich membranes. Since cardiac function in physiological conditions was not affected by the diet, fish oil could be considered as a beneficial factor to limit heart injury during ischemia and reperfusion.
authors.affiliation: INRA, Station de Recherches sur la Qualité des Aliments de l'Homme, Unité de Nutrition Lipidique, Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Demaison
authors.forename: J P
authors.initials: JP
authors.lastname: Sergiel
authors.forename: D
authors.initials: D
authors.lastname: Moreau
authors.forename: A
authors.initials: A
authors.lastname: Grynberg
mesh_terms: D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage* / Q000378:metabolism; D004734:Energy Metabolism; D015525:Fatty Acids, Omega-3 / Q000032:analysis*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000032:analysis*; D006439:Hemodynamics; D007425:Intracellular Membranes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D010743:Phospholipids; D007770:L-Lactate Dehydrogenase