© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Beneficial effects of propionyl L-carnitine on sarcolemmal changes in congestive heart failure due to myocardial infarction
aInstitute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
bDivisione di Cardiologia, Universita Degli Studi di Brescia, Brescia, Italy
cvso{at}sbrc.umanitoba.ca
* Corresponding author. Tel.: +1-204-235-3417; fax: +1-204-233-6723
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 µmol 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.
KEYWORDS Rat sarcolemma; Na+–K+ ATPase; Adenylate cyclase; Na+–Ca2+ exchange; Propionyl L-carnitine
1 Present address: Department of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
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