Effect of coenzyme Q10 supplementation on mitochondrial function after myocardial ischemia reperfusion

Background. Coenzyme Q(10) (CoQ(10)) protects myocardium from ischemia-reperfusion (IR) injury as evidenced by improved recovery of mechanical function, ATP, and phosphocreatine during reperfusion. This protection may result from CoQ(10)'s bioenergetic effects on the mitochondria, from its antioxidant properties, or both. The purpose of this study was to elucidate the effects of CoQ(10) supplementation on mitochondrial function during myocardial ischemia-reperfusion using an isolated mitochondrial preparation. Methods. Isolated hearts (n = 6/group) from rats pretreated with liposomal CoQ(10) (10 mg/kg iv, CoQ(10)), vehicle (liposomal only, Vehicle), or saline (Saline) 30 min before the experiments were subjected to 15 min of equilibration (EQ), 25 min of ischemia (I), and 40 min of reperfusion (RP). Left ventricular-developed pressure (DP) was measured. Mitochondria were isolated at end-equilibration (end-EQ), at end-ischemia (end-I), and at end-reperfusion (end-RP). Mitochondrial respiratory function (State 2, 3, and 4, respiratory control index (RCI, ratio of State 3 to 4), and ADP:O ratio) was measured by polarography using NADH (alpha-ketoglutarate, alpha-KG)- or FADH (succinate, SA)-dependent substrates. Results. CoQ(10) improved recovery of DP at end-RP (67 +/- 11% in CoQ(10) vs 47 +/- 5% in Vehicle and 50 +/- 11% in Saline, P < 0.05 vs Vehicle and Saline). CoQ(10) did not change preischemic mitochondrial function. IR decreased State 3 and RCI in all groups using either substrate. CoQ(10) had no effect in the mitochondrial oxidation of alpha-KG at end-I. CoQ(10) improved State 3 at end-I when SA was used (167 +/- 21 in CoQ(10) vs 120 +/- 10 in Saline and 111 +/- 10 ng-atoms O/min/mg protein in Vehicle, P < 0.05). Using alpha-KG as a substrate, CoQ(10) improved RCI at end-RP (4.2 +/- 0.2 in CoQ(10) vs 3.2 +/- 0.2 in Saline and 3.0 +/- 0.3 in Vehicle, P < 0.05). Using SA, CoQ(10) improved State 3 (181 +/- 10 in CoQ(10) vs 142 +/- 9 in Saline and 140 +/- 12 ng-atoms O/min/mg protein in Vehicle, P < 0.05) and RCI (2.21 +/- 0.06 in CoQ(10) vs 1.85 +/- 0.11 in Saline and 1.72 +/- 0.08 in Vehicle, P < 0.05) at end-RP. Conclusions. The cardioprotective effects of CoQ(10) can be attributed to the preservation of mitochondrial function during reperfusion as evidenced by improved FADH-dependent oxidation. (C) 2001 Elsevier Science.