Cardiomiopatías químicas: Repercusión funcional de la cloroquina en corazón aislado.

Chloroquine, is a drug used in the treatment and prophylaxis of plasmodium related diseases, such as malaria. It is also used in the treatment of rheumatoid arthritis, chronic lupus erythematosus or neoplasms. It has a toxic collateral effect and deaths have been reported in patients who have used it. One of the targets of CQ toxicity is the heart. The pathophysiological features of heart failure caused by acute exposure to chloroquine are poorly characterized.This paper characterizes the effects of acute exposure to chloroquine at the cardiac level, trying to understand how this drug may impair heart function. Our findings indicate that cholorquine has a negative inotropic effect (mean effect dose, IC50 ~ 5 μM), being reversible at low concentrations. The kinetics of promotion and wash-out are extremely fast (seconds). Chloroquine has also an arrhythmogenic and a negative chronotropic effect, with a slightly higher IC50. Doses exceeding 100 μM, almost fully impair contractile activity, though electrical activity can still be observed. These doses also block L-type Ca2+ currents, partially explaining the negative inotropic effect of the drug inhibiting calcium induced calcium release.The results indicate that acute exposure to chloroquine in the μM range, impair heart function at the contractile and electrical levels, with a different sensitivity for both, suggesting multiple mechanisms of action of this drug, presumably related to its ability to cause chemical cardiomyopathy, from among which, L-type Ca2+ channels might be implicated.