Studies of hypoxemic/reoxygenation injury: without aortic clamping. VII. Counteraction of oxidant damage by exogenous antioxidants: coenzyme Q10.
Coenzyme Q10 (CoQ10) is a natural mitochondrial respiratory chain constituent with antioxidant properties. This study tests the hypothesis that CoQ10 administered before the onset of reoxygenation on cardiopulmonary bypass, can reduce oxygen-mediated myocardial injury and avoid myocardial dysfunction after cardiopulmonary bypass. The antioxidant properties of CoQ10 were confirmed by an in vitro study in which normal myocardial homogenates were incubated with the oxidant, t-butylhydroperoxide. Fifteen immature piglets (< 3 weeks old) were placed on 60 minutes of cardiopulmonary bypass. Five piglets underwent cardiopulmonary bypass without hypoxemia (oxygen tension about 400 mm Hg). Ten others became hypoxemic on cardiopulmonary bypass for 30 minutes by lowering oxygen tension to approximately 25 mm Hg, followed by reoxygenation at oxygen tension about 400 mm Hg for 30 minutes. In five piglets, CoQ10 (45 mg/kg) was added to the cardiopulmonary bypass circuit 15 minutes before reoxygenation, and five others were not treated (no treatment). Myocardial function after cardiopulmonary bypass was evaluated from end-systolic elastance (conductance catheter), oxidant damage (lipid peroxidation) was assessed by measuring conjugated diene levels in coronary sinus blood, and antioxidant reserve capacity was determined by measuring malondialdehyde in myocardium after cardiopulmonary bypass incubated in the oxidant, t-butylhydroperoxide. Cardiopulmonary bypass without hypoxemia caused no oxidant damage and allowed complete functional recovery. Reoxygenated hearts (no treatment) showed a progressive increase in conjugated diene levels in coronary sinus blood after reoxygenation (2.3 +/- 0.6 A233 nm/0.5 ml plasma at 30 minutes after reoxygenation) and reduced antioxidant reserve capacity (malondialdehyde: 1219 +/- 157 nmol/g protein at 4.0 mmol/L t-butylhydroperoxide), resulting in severe postbypass dysfunction (percent end-systolic elastance = 38 +/- 6). Conversely, CoQ10 treatment avoided the increase in conjugated diene levels (2.1 +/- 0.6 vs 1.1 +/- 0.3, p < 0.05 vs no treatment), retained normal antioxidant reserve (896 +/- 76 nmol/g protein, p < 0.05 vs no treatment), and allowed nearly complete recovery of function (94% +/- 7%, p < 0.05 vs no treatment). We conclude that reoxygenation of the hypoxemic immature heart on cardiopulmonary bypass causes oxygen-mediated myocardial injury, which can be limited by CoQ10 treatment before reoxygenation. These findings imply that coenzyme Q10 can be used to surgical advantage in cyanotic patients, because therapeutic blood levels can be achieved by preoperative oral administration of this approved drug.
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D003067:Coenzymes; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000150:complications* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D010545:Peroxides / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species; D013552:Swine; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D020122:tert-Butylhydroperoxide
D003067:Coenzymes; D010545:Peroxides; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D020122:tert-Butylhydroperoxide; C024989:coenzyme Q10