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

Objective: 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. Methods: 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. Results: 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 mu mol Pi/mg/h, respectively. Furthermore, the SL Na+-dependent Ca2+-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. Conclusion: 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. (C) 1999 Elsevier Science B.V. All rights reserved.