BMS309403 directly suppresses cardiac contractile function.

BMS309403, a substance used as an inhibitor of adipocyte fatty acid-binding protein, has been suggested as a new therapeutic agent for treating type 2 diabetes mellitus and atherosclerosis; however, little is known about its possible side effects. The present study investigates the effects of BMS309403 on the cardiovascular system. We used isolated perfused heart preparations and single cardiomyocytes from adult rats for contractile analysis. The Ca(2+) sensitivity of the myofilaments was investigated by using porcine cardiac skinned muscle fibers. BMS309403 induced a negative effect on the contractility of isolated perfused hearts leading to heart arrest without interfering in the electrocardiographic activity, suggesting electromechanical dissociation. Experiments with isolated cardiomyocytes showed that BMS309403 had a direct biphasic inhibitory effect on cardiomyocyte contraction, at higher concentrations by attenuating Ca(2+) levels. This negative inotropic effect does not result from a direct effect on the myofilaments. BMS309403 has an acute cardiac depressant effect in vitro. The potential therapeutic applicability of this compound requires additional consideration.