Acute administration of liposomal coenzyme Q10 increases myocardial tissue levels and improves tolerance to ischemia reperfusion injury.
The antioxidant and bioenergetic effects of CoQ10 (CoQ) suggest it might be ideal therapy for acute myocardial ischemia. Its utility is limited by the requirement for enteral administration. This study related the administration of a new liposomal suspension of CoQ given intravenously to (1) serum and myocardial [CoQ] and (2) recovery of function, myocardial efficiency, and oxidant injury after cardiac ischemia and reperfusion (I/R). Rats (n = 8/group) were given liposomal CoQ 10 mg/kg iv or placebo (Control), 15 min (C-15), 30 min (C-30), and 60 min (C-60) before (1) measurement of serum and myocardial CoQ or (2) Langendorff perfusion of hearts subjected to 15 min equilibration, 25 min ischemia (37 degrees C), and 40 min reperfusion (RP). Developed pressure (DP) was measured via an intraventricular balloon and coronary flow was measured by a digital flow meter. Myocardial efficiency was defined as DP/MVO2 where MVO2 = microl O2 consumed/min/gram LV. At end RP hearts were assayed for CK, an oxidant sensitive enzyme. Maximum preischemic CoQ levels in serum and myocardium occurred 15 and 30 min after administration, respectively. At end reperfusion, C-30 hearts improved the most, recovering 75 +/- 4% of their preischemic DP while Control recovered only 52 +/- 6% (P < 0.03) as well as maintaining better myocardial efficiency (0.69 +/- 0.02 vs Control, 0.43 +/- 0.05) (P < 0.001). C-15, C-30, and C-60 groups all lost less CK activity after RP vs Control (P < 0.04).


CONCLUSIONS
(1) Serum and myocardial levels of CoQ can be raised acutely by iv liposomal CoQ. (2) Myocardial CoQ levels correlate best with I/R protection. (3) Acute iv CoQ improves function and efficiency and decreases oxidant injury after I/R. Intravenous CoQ may be effective clinically for acute cardiac ischemic syndromes.
Division of Cardiothoracic Surgery, Allegheny University/MCP, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, USA.
K
K
Niibori
H
H
Yokoyama
J A
JA
Crestanello
G J
GJ
Whitman
D000818:Animals; D003067:Coenzymes; D003402:Creatine Kinase / Q000378:metabolism; D004198:Disease Susceptibility; D004337:Drug Carriers; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008081:Liposomes; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
D003067:Coenzymes; D004337:Drug Carriers; D008081:Liposomes; D014451:Ubiquinone; D003402:Creatine Kinase; C024989:coenzyme Q10