ELUCIDATION OF A TRIPARTITE MECHANISM UNDERLYING THE IMPROVEMENT IN CARDIAC TOLERANCE TO ISCHEMIA BY COENZYME Q(10) PRETREATMENT

Coenzyme Q(10), which is involved in mitochondrial adenosine triphosph ate production, is also a powerful antioxidant, We hypothesize that co enzyme Q(10) pretreatment protects myocardium from ischemia reperfusio n injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during repe rfusion, Isolated hearts (six per group) from rats pretreated with eit her coenzyme Q(10), 20 mg/kg intramuscularly and 10 mg/kg intraperiton eally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes o f ischemia, and 40 minutes of reperfusion, Developed pressure, contrac tility, compliance, myocardial oxygen consumption, and myocardial aero bic efficiency were measured, Phosphorus 31 nuclear magnetic resonance (P-31-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diph osphonic acid standard, Hearts were assayed for myocardial coenzyme Q( 10) and myocardial creatine kinase activity at end equilibration and a t reperfusion, Treated hearts showed higher myocardial coenzyme Q(10) levels (133 +/- 5 mu g/gm ventricle versus 117 +/- 4 mu g/gm ventricle , p < 0.05), Developed pressure at end reperfusion was 62% +/- 2% of e quilibration in treatment group versus 37% +/- 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was presented durin g reperfusion in treatment group (0.84 +/- 0.08 mm Hg/(mu l O-2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(mu l O-2/min/gm ventricle) at equi libration,p = not significant), whereas in the control group it fell t o 0.62 +/- 0.07 mm Hg/(mu l O-2/min/gm ventricle, p < 0.05 vs equilibr ation and vs the treatment group at reperfusion, Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% +/- 2% for the treatment gro up vs 33% +/- 3% in the control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treat ment group vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphoc reatine 45% +/- 2% in the treatment group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05), Coenzyme Q,, pretreatment improves myoca rdial function after ischemia and reperfusion, This results from a tri partite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myoca rdial aerobic efficiency during reperfusion, and (3) protection of cre atine kinase from oxidative inactivation during reperfusion.