Exercise intolerance during post-MI heart failure in rats: prevention with supplemental dietary propionyl-L-carnitine.
Exercise capacity in patients with several types of cardiovascular disease can be improved with dietary carnitine, or carnitine derivatives. Mechanisms underlying this improvement remain largely unknown in part due to a lack of animal models of cardiac pathology in which carnitine derivatives improve exercise tolerance. Our goal was to evaluate the ability of propionyl-L-carnitine (PLC) to improve exercise tolerance in a rat model of exercise intolerance. Fischer 344 rats were followed after either a moderate size MI (n = 22) or sham MI surgery (n = 14). Starting 10 days post-surgery 10 of the MI and 7 of the sham rats received 100 mg/kg/day PLC in drinking water, which increased plasma and LV total l-carnitine concentrations 15-23% (p < 0.05). Rats were followed longitudinally until a statistically significant decrease in exercise capacity occurred in one of the groups, at which time all rats were sacrificed for study of the isolated perfused hearts. At 12-weeks post-MI exercise capacity had decreased 16 +/- 7% (p < 0.05) in the MI group, but remained within 3% of baseline in the MI group that received PLC and the sham groups. Both MI groups exhibited the same degree of LV dilation, decrease in fractional shortening, and blunting of the response to isoproterenol. We conclude that supplemental dietary PLC attenuates the exercise intolerance that occurs secondary to post-MI heart failure in rats, but that this beneficial effect is not attributable to altered LV remodeling, an improved response to beta-adrenergic stimulation, or increased skeletal muscle citrate synthase activity.
Koh
Stanley G
SG
Cardiac Muscle Research Laboratory, Boston University School of Medicine, 650 Albany St, X720, Boston, MA 02118, USA.
Brenner
Daniel A
DA
Korzick
Donna H
DH
Tickerhoof
Marlena M
MM
Apstein
Carl S
CS
Saupe
Kurt W
KW
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004032:Diet; D004195:Disease Models, Animal; D017079:Exercise Tolerance / Q000187:drug effects*; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D016277:Ventricular Function, Left / Q000187:drug effects
C003223:propionylcarnitine; D002331:Carnitine