Functional and metabolic effects of propionyl-L-carnitine in the isolated perfused hypertrophied rat heart.
Aim of this study was to assess the effect of propionyl-L-carnitine (PLC), a naturally occurring derivative of L-carnitine, in cardiac hypertrophy induced by pressure overload in rats. The abdominal aorta was banded and the rats received one daily administration of PLC (50 mg/kg) or saline for four days. The hearts were excised 24 h after the last administration and were perfused retrogradely with oxygenated Krebs-Henseleit buffer containing 1.2 mM palmitate bound to 3% (w/v) albumin, 2.5 microM PLC and 25 microM L-carnitine. A saline-filled balloon was inserted into the left ventricle and the heart contractility was measured at three volumes of the balloon, corresponding to zero diastolic pressure and to increased volumes (110 and 220 microliters) over the zero volume. At the end of the perfusion, the hearts were freeze-clamped, weighed and analyzed for adenine nucleotide and phosphocreatine (PCr) content by HPLC methods. No differences in the myocardial performance were found at zero diastolic pressure. In contrast, at high intraventricular volume, the maximal rate of ventricular relaxation was increased in PLC-treated with respect to saline-treated controls (p < 0.05). In addition, the increase of the end-diastolic pressure at increasing balloon volume was more marked in controls than in the PLC-treated hearts (p < 0.02). These data correlate well with the measured higher level of total adenine nucleotides (p < 0.05) and ATP (p < 0.02) in the PLC-treated hearts, while PCr was the same in both groups. Parallel experiments performed in the absence of palmitate in the perfusing media failed to show any effect of PLC.(ABSTRACT TRUNCATED AT 250 WORDS)
Motterlini
R
R
Istituto Scientifico San Raffaele, Dipartimento di Scienze e Tecnologie Biomediche, Università di Milano, Italy.
Samaja
M
M
Tarantola
M
M
Micheletti
R
R
Bianchi
G
G
D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002331:Carnitine / Q000031:analogs & derivatives* / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects
D002316:Cardiotonic Agents; D005227:Fatty Acids; C003223:propionylcarnitine; D002331:Carnitine