Effect of propionyl-l-carnitine and enalapril on cardiac function of pressure-overloaded rats during increase in load.
Chronic administration of propionyl-l-carnitine has been recently shown to correct hypertrophy related abnormalities in muscle mechanics. Accordingly, this study investigated whether the drug would similarly improve cardiac dynamics in rats with pressure overload. Enalapril was used for comparison. Drugs were administered in the drinking water for 3 weeks to Wistar Kyoto rats with a 2 week abdominal aortic constriction. Cardiac function was studied under urethane anaesthesia in basal conditions, during increase in preload, and during increase in afterload. Basal cardiac function was comparable in pressure-overloaded and sham-operated animals. Neither propionyl-l-carnitine nor enalapril affected the basal performance. Compared to sham-operated animals, untreated pressure-overloaded rats showed an impaired cardiac response (cardiac output, stroke volume) to preload increase induced by saline i.v. infusion. Propionyl-l-carnitine dose dependently improved cardiac function in the range 30-180 mg/kg, without affecting cardiac hypertrophic growth. Enalapril (3 mg/kg) reduced cardiac hypertrophy and improved cardiac function. The two effects were unrelated. The afterload increase by total aortic occlusion evidenced a reduction in the left ventricle pressure generating capacity of hypertrophied hearts. Propionyl-l-carnitine did not modify this parameter, while enalapril afforded a significant improvement. Results show that propionyl-l-carnitine significantly improves in vivo cardiac dynamics under conditions of increased energy demand. The effect is not due to inotropic efficacy, but presumably to increased cardiac efficiency.
Micheletti
R
R
Prassis Sigma-tau Research Institute, Settimo Milanese, Italy.
Donato di Paola
E
E
Schiavone
A
A
Rossi
R
R
Bianchi
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; C003223:propionylcarnitine; D004656:Enalapril; D002331:Carnitine