FUNCTIONAL AND METABOLIC EFFECTS OF PROPIONYL-L-CARNITINE IN THE ISOLATED PERFUSED HYPERTROPHIED RAT-HEART

被引:26
作者
MOTTERLINI, R
SAMAJA, M
TARANTOLA, M
MICHELETTI, R
BIANCHI, G
机构
[1] UNIV HILANO,IST SCI SAN RAFFAELE,DIPARTIMENTO SCI & TECNOL BIOMED,VIA OLGETTINA 60,I-20132 MILAN,ITALY
[2] PRASSIS SIGMA TAU INST,MILAN,ITALY
关键词
ISOLATED HEART; PROPIONYL-L-CARNITINE; PALMITIC ACID; ENERGETIC METABOLITES;
D O I
10.1007/BF01270581
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 muM PLC and 25 muM 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 mul) 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. We conclude that PLC improves the diastolic function by increasing the fraction of energy available from fatty acid oxidation in the form of ATP.
引用
收藏
页码:139 / 145
页数:7
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