Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic and ischemic stress: studies in rats and in human atrial tissue.
The inferior recovery of cardiac function after interventional cardiac procedures in elderly patients compared to younger patients suggests that the aged myocardium is more sensitive to stress. We report two studies that demonstrate an age-related deficit in myocardial performance after aerobic and ischemic stress and the capacity of CoQ10 treatment to correct age-specific diminished recovery of function. In Study 1 the functional recovery of young (4 mo) and senescent (35 mo) isolated working rat hearts after aerobic stress produced by rapid electrical pacing was examined. After pacing, the senescent hearts, compared to young, showed reduced recovery of pre-stress work performance. CoQ10 pretreatment (daily intraperitoneal injections of 4 mg/kg CoQ10 for 6 weeks) in senescent hearts improved their recovery to match that of young hearts. Study 2 tested whether the capacity of human atrial trabeculae (obtained during surgery) to recover contractile function, following ischemic stress in vitro (60 min), is decreased with age and whether this decrease can be reversed by CoQ10. Trabeculae from older individuals (> or = 70 yr) showed reduced recovery of developed force after simulated ischemia compared to younger counterparts (< 70 yr). Notably, this age-associated effect was prevented in trabeculae pretreated in vitro (30 min at 24 degrees C) with CoQ10 (400 MicroM). We measured significantly lower CoQ10 content in trabeculae from > or = 70 yr patients. In vitro pretreatment raised trabecular CoQ10 content to similar levels in all groups. We conclude that, compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre-stress contractile performance, however, this reduction is attenuated by CoQ10 pretreatment.
Cardiac Surgical Research Unit, Baker Medical Research Institute, Prahran, Vic., Australia.
F L
FL
Rosenfeldt
S
S
Pepe
R
R
Ou
J A
JA
Mariani
M A
MA
Rowland
P
P
Nagley
A W
AW
Linnane
D000332:Aerobiosis; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003067:Coenzymes; D005260:Female; D006321:Heart / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D006325:Heart Atria; D006801:Humans; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; C024989:coenzyme Q10