The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury.
It has been hypothesized that CoQ10 (CoQ) pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 and 2 h prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP). Developed pressure, +/-dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol. CoQ pretreatment improved myocardial function after ischemia reperfusion. CoQ pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ. Similarly it was hypothesized that CoQ protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed lyposomal CoQ preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R. We conclude that CoQ pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.
Whitman
G J
GJ
Division of Cardiothoracic Surgery, Allegheny University Hospitals, Philadelphia, PA 19129, USA.
Niibori
K
K
Yokoyama
H
H
Crestanello
J A
JA
Lingle
D M
DM
Momeni
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001920:Bradykinin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003067:Coenzymes; D003331:Coronary Vessels / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D003067:Coenzymes; D016166:Free Radical Scavengers; D014451:Ubiquinone; D009599:Nitroprusside; D000255:Adenosine Triphosphate; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; C024989:coenzyme Q10; D013890:Thiourea; D001920:Bradykinin