Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect

• Published in: Surgery 1996-08, Vol.120 (2), p.189-196
• Main Authors: Yokoyama, H, Lingle, D M, Crestanello, J A, Kamelgard, J, Kott, B R, Momeni, R, Millili, J, Mortensen, S A, Whitman, G J
• Format: Article
• Language: English
• Subjects: Acridines; Animals; Antioxidants - pharmacology; Bradykinin - pharmacology; Coenzymes; Coronary Circulation - drug effects; Endothelium, Vascular - drug effects; Hydrogen Peroxide; Luminescent Measurements; Male; Myocardial Ischemia - drug therapy; Nitroprusside - pharmacology; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology; Ventricular Function, Left - drug effects
• ISSN: 0039-6060
• DOI: 10.1016/S0039-6060(96)80287-X

Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been recognized as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after I/R via an antioxidant mechanism. Rats were pretreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment. Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion-induced oxidative burst was directly assessed by lucigenin enhanced chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated. I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/- 0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early period of reperfusion. Endothelium-dependent vasorelaxation is more sensitive than endothelium-independent relaxation to I/R injury. Via a direct antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.