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Published on: March 18, 2019
Antimony-induced cardiomyopathy in guinea-pig and protection by L-carnitine
Marco Alvarez1, Claire O Malécot, François Gannier
1CNRS UMR 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences, Parc de Grandmont, 37200 Tours, France.
Abstract:
Antimony (Sb) is the mainstay for the treatment of Leishmaniasis. It has serious, often lethal, cardiovascular side effects. The objective of this study was to examine the effects of Sb treatment upon the electrocardiogram (ECG), myocyte contractility (assessed by monitoring sarcomere length during field stimulation), whole-cell action potential (AP) and calcium current (I(Ca)) of the guinea-pig and to evaluate L-carnitine as a cardioprotective agent. Guinea-pigs received daily injections of either saline, Sb(V), Sb(III), L-carnitine or L-carnitine with Sb(III). Eight lead ECGs were recorded under halothane anaesthesia every 4 days. At the end of each treatment regime, animals were killed and ventricular myocytes were enzymatically isolated. Treatment with Sb(V) for 26 days prolonged the QT interval of the ECG. Treatment with Sb(III) was lethal within 2 days for approximately 50% of the animals. The survivors showed ECG alterations similar to those described in man: T wave flattening and/or inversion, depression of the ST segment, and elongation of RR and QT intervals. Their ventricular myocytes showed impaired contraction responses to changes in stimulus frequency, elongated AP and reduced I(Ca). Combined treatment with L-carnitine and Sb(III) delayed mortality. Prior treatment with L-carnitine followed by combined treatment with L-carnitine and Sb(III) reduced mortality to <10% over 12 days and these animals showed normal ECG. Their myocytes showed normal contractility and AP. It is concluded that L-carnitine has a preventive cardioprotective role against antimony-induced cardiomyopathy. The mechanism of action of L-carnitine may be to counter oxidative stress caused by Sb(III).
Insights
Antimony treatments for leishmaniasis cause severe heart problems. L-carnitine effectively prevents antimony-induced cardiomyopathy by protecting heart cells and function.
Area of Science:
- Cardiology
- Pharmacology
- Parasitology
Background:
- Antimony compounds are essential for treating leishmaniasis but cause significant cardiovascular toxicity.
- Cardiotoxicity includes ECG abnormalities, impaired myocyte function, and altered action potentials.
Purpose of the Study:
- To investigate the cardiovascular effects of antimony (Sb) treatment in guinea pigs.
- To evaluate the cardioprotective potential of L-carnitine against Sb-induced cardiotoxicity.
Main Methods:
- Guinea pigs were treated with saline, Sb(V), Sb(III), L-carnitine, or L-carnitine with Sb(III).
- Electrocardiograms (ECGs) and ventricular myocyte function (contractility, action potential, calcium current) were assessed.
- Mortality rates and ECG/myocyte parameters were compared between treatment groups.
Main Results:
- Sb(V) prolonged QT interval; Sb(III) caused high mortality and ECG changes (T wave flattening, ST depression, prolonged RR/QT).
- Sb(III) impaired myocyte contractility, action potential, and calcium current.
- L-carnitine co-administration or pre-treatment significantly reduced Sb(III)-induced mortality and protected against ECG and myocyte dysfunction.
Conclusions:
- L-carnitine demonstrates a preventive cardioprotective effect against antimony-induced cardiomyopathy.
- L-carnitine may counteract Sb(III)-induced cardiotoxicity, potentially by mitigating oxidative stress.
