Beneficial effects of propionyl L-carnitine on sarcolemmal changes in congestive heart failure due to myocardial infarction

• Published in: Cardiovascular research 1999-06, Vol.42 (3), p.607-615
• Main Authors: SETHI, R, DHALLA, K. S, GANGULY, P. K, FERRARI, R, DHALLA, N. S
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Calcium - metabolism; Cardiology. Vascular system; Carnitine - analogs & derivatives; Carnitine - therapeutic use; Coronary heart disease; Heart; Heart Failure - drug therapy; Heart Failure - etiology; Heart Failure - metabolism; Male; Medical sciences; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Rats; Rats, Sprague-Dawley; Sarcolemma - drug effects; Sarcolemma - enzymology; Sodium-Calcium Exchanger - drug effects; Sodium-Potassium-Exchanging ATPase - metabolism; Time Factors; Ventricular Dysfunction, Left - drug therapy
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(99)00089-9

Earlier studies have revealed sarcolemmal (SL) defects in congestive heart failure due to myocardial infarction; however, the mechanisms of SL changes in the failing heart are poorly understood. Since congestive heart failure is associated with various metabolic abnormalities including a deficiency of carnitine, we examined the effects of propionyl L-carnitine, a carnitine derivative, in animals with congestive heart failure. For this purpose, heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated with 100 mg/kg (i.p. daily) propionyl L-carnitine for 4 weeks. The sham control group received saline injections. The animals were assessed for their left ventricular function. SL membranes were examined for Na(+)-K+ ATPase, Na(+)-Ca2+ exchange and adenylate cyclase activities. A marked improvement in the attenuated left ventricular function of the experimental animals was seen upon treatment with propionyl L-carnitine. The SL adenylyl cyclase activities in control, untreated failing hearts and treated failing hearts were 590 +/- 36, 190 +/- 22 and 320 +/- 21 pmol cAMP/mg/10 min, whereas the SL Na(+)-K+ ATPase activities were 35.7 +/- 2.8, 22.5 +/- 2.4 and 30.1 +/- 2.8 mumol Pi/mg/h, respectively. Furthermore, the SL Na(+)-dependent Ca(2+)-uptake activity, which decreased in the failing hearts (4.6 +/- 0.4 vs. 9.3 +/- 0.7 nmol Ca2+/mg/2 s for control), was improved (6.8 +/- 0.5 nmol Ca2+/mg/2 s) significantly following treatment with propionyl L-carnitine. These results indicate that metabolic therapy with propionyl L-carnitine may attenuate defects in the SL membrane and thus may improve heart function in congestive heart failure due to myocardial infarction.