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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yokoyama
H
H
Department of Cardiothoracic Surgery, Medical College of Pennsylvania, Philadelphia, USA.
Lingle
D M
DM
Crestanello
J A
JA
Kamelgard
J
J
Kott
B R
BR
Momeni
R
R
Millili
J
J
Mortensen
S A
SA
Whitman
G J
GJ
D000166:Acridines; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D003067:Coenzymes; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D006861:Hydrogen Peroxide; D008163:Luminescent Measurements; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D000166:Acridines; D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; D009599:Nitroprusside; C033472:10,10'-dimethyl-9,9'-biacridinium; D006861:Hydrogen Peroxide; C024989:coenzyme Q10; D001920:Bradykinin