Possible mechanism by which coenzyme Q10 improves reoxygenation-induced recovery of cardiac contractile force after hypoxia.
To elucidate possible mechanisms by which coenzyme Q10 enhances reoxygenation-induced recovery of cardiac contractile force after hypoxia, rabbit hearts were subjected to hypoxic perfusion for 20 min, followed by 45 min-reoxygenation with or without pretreatment with coenzyme Q10. Hypoxia induced a decline in cardiac contractile force, a decrease in myocardial high-energy phosphates and a release of ATP metabolites and creatine phosphokinase from the perfused heart. Upon reoxygenation the rate of release of ATP metabolites subsided, but no appreciable recovery of the loss of contractile force and the reduction of myocardial ATP content was seen, and the release of creatine phosphokinase was increased further. Pretreatment of rabbits with coenzyme Q10 resulted in an appreciable recovery of cardiac contractile force and of myocardial ATP content upon reoxygenation. The release of creatine phosphokinase from hearts during hypoxia and reoxygenation was inhibited completely by the pretreatment. Changes in the UV absorbance of the perfusate suggested that coenzyme Q10 reduced the loss of ATP metabolites from hypoxic hearts. Furthermore, high-performance liquid chromatographic analysis indicated that coenzyme Q10 attenuated the release of inosine and hypoxanthine from the hearts and decreased myocardial inosine and adenosine content of the hypoxic heart, suggesting that coenzyme Q10 retards the breakdown of ATP metabolites which are possible substrates for a salvage synthesis of ATP, when oxygen is replenished. This could account for an appreciable restoration of ATP, and eventually provide a significant recovery of cardiac contractile force upon reoxygenation.
Takeo
S
S
Department of Physiology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
Tanonaka
K
K
Tazuma
Y
Y
Miyake
K
K
Murai
R
R
D000241:Adenosine / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003067:Coenzymes; D003402:Creatine Kinase / Q000032:analysis; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007288:Inosine / Q000032:analysis; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000032:analysis; D010100:Oxygen / Q000494:pharmacology*; D010477:Perfusion; D010725:Phosphocreatine / Q000032:analysis; D011817:Rabbits; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology
D003067:Coenzymes; D010725:Phosphocreatine; D014451:Ubiquinone; D007288:Inosine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; C024989:coenzyme Q10; D000241:Adenosine; D010100:Oxygen