Propionyl-L-carnitine prevents myocardial mechanical alterations due to pressure overload in rats.
This study investigated if propionyl-L-carnitine (PLC) treatment can directly affect cardiac mechanics, secondary to increase in myocardial carnitine content, in rats with aortic constriction and sham-operated controls. After weaning, rats were fed one of the following diets for 8 wk: 1) a low-carnitine diet (containing 2 nmol/g carnitine); 2) the same diet supplemented with PLC (710 mumol/kg body wt); 3) L-carnitine (LC; 118 mumol/kg body wt, given in tap water; or 4) a standard diet (containing 56 nmol/g carnitine). A 4-wk constriction of the abdominal aorta caused left ventricular hypertrophy associated with significantly prolonged timing parameters and reduced rate of tension decay in papillary muscles. In group 2, however, PLC treatment prevented hypertrophy-induced changes in these parameters and the reduction in unloaded shortening velocity in skinned trabeculae. Finally, PLC treatment maintained the relative proportion of myosin heavy chain isoforms in left ventricular wall of animals subjected to aortic constriction. Both PLC and LC completely prevented carnitine depletion due to hypertrophy and to dietary restriction. Because LC did not modify papillary muscle contractile function, these results demonstrate that PLC affects hypertrophy-induced changes in muscle mechanics and ventricular wall composition independently of tissue carnitine levels.
Prassis Istituto di Ricerche Sigma-Tau, Milan, Italy.
R
R
Micheletti
G
G
Giacalone
M
M
Canepari
S
S
Salardi
G
G
Bianchi
C
C
Reggiani
D000818:Animals; D001011:Aorta; D006332:Cardiomegaly / Q000209:etiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003251:Constriction, Pathologic; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006352:Heart Ventricles; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D009218:Myosins; D002331:Carnitine