Coenzyme Q10 enhances cardiac functional and metabolic recovery and reduces Ca2+ overload during postischemic reperfusion.
The effects of coenzyme Q10 (CoQ) were studied in isolated, isovolumic rat hearts during a 30-min period of global ischemia followed by 40 min of reperfusion. After reperfusion 1) the relative recovery of developed pressure (DP) was increased by CoQ (75 vs. 40% of the preischemic value for 20 microM CoQ and control hearts, respectively, P < 0.001); 2) diastolic pressure elevation was decreased by CoQ (20 vs. 50 mmHg in CoQ vs. control hearts, respectively, P < 0.001); and 3) recovery of high-energy phosphates and reduction of inorganic phosphate were approximately twofold greater in CoQ vs. control hearts (P < 0.001 for each parameter). The beneficial effects of CoQ were not observed when CoQ was added at the onset of reperfusion. The total free generation during reperfusion was not affected by CoQ. In unpaced hearts, in the presence of verapamil to prevent spontaneous beating, spontaneous Ca2+ oscillations were measured as scattered laser light intensity fluctuations (SLIF). The transient rise in SLIF in the postischemic reperfused myocardium, which previously has been shown to predict the extent of Ca2+ overload, was suppressed by CoQ (P < 0.001). These results suggest that while early CoQ treatment does not scavenge the primary burst of superoxide or hydroxy radical generation, which occurs on reperfusion, it markedly improves the functional recovery during reperfusion by enhancing the recovery of high-energy phosphates and preventing Ca2+ overload.
Hano
O
O
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Thompson-Gorman
S L
SL
Zweier
J L
JL
Lakatta
E G
EG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003067:Coenzymes; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007834:Lasers; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012146:Rest; D012542:Scattering, Radiation; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D003067:Coenzymes; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C024989:coenzyme Q10; D002118:Calcium