L-carnitine supplementation improves right ventricular contractility by increasing fatty acid oxidation and reducing lipid accumulation, according to a new study published in the journal Pulmonary Circulation.
Based on this finding, the authors concluded that correcting carnitine deficiency by L-carnitine supplementation could reverse right ventricular failure in pulmonary arterial hypertension (PAH).
Right ventricular failure, the main cause of death in patients with PAH, is, in part, the result of reduced fatty acid oxidation and lipid accumulation that is toxic to cells. The authors of the present study hypothesized that this could be driven, at least in part, by a relative carnitine deficiency.
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The team led by Evan L. Brittain MD, MSCI, from the Department of Medicine, Division of Cardiovascular Medicine at Vanderbilt University Medical Center, in Nashville, Tennessee, tested their hypothesis using plasma collected from patients with PAH and healthy volunteers as well as rat myoblasts and transgenic mice.
Read more about the pathophysiology of PAH.
The team found that the ratio of long chain fatty acid to carnitine is increased in patients with PAH, compared to healthy volunteers.
Then using a mouse model of PAH, the researchers showed that L-carnitine supplementation reversed right ventricular failure by increasing right ventricular cardiac output, improving right ventricular ejection fraction, and decreasing right ventricular lipid accumulation. It also decreased fatty acid accumulation in the right ventricle and increased acylcarnitines.
Finally, using cells grown in culture, the researchers showed that L-carnitine supplementation increased fatty acid oxidation and decreased lipid accumulation.
They concluded that L-carnitine supplementation should further be explored as a potential therapeutic strategy for PAH in the future.
There is currently no effective treatment available for right ventricular failure, so therapies that can improve right ventricular function are urgently needed.
Reference
Agrawal V, Hemnes AR, Shelburne NJ, et al. L-carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation. Pulm Circ. 2022;12,3, e12107. doi:10.1002/pul2.12107
