Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: a Translational Study
Raffaele Coppini, Cecilia Ferrantini, Josè Manuel Pioner, Lorenzo Santini, Zhinuo J. Wang, Chiara Palandri, Marina Scardigli, Giulia Vitale, Leonardo Sacconi, Pierluigi Stefàno, Laura Flink, Katherine Riedy, Francesco Saverio Pavone, Elisabetta Cerbai, Corrado Poggesi, Alessandro Mugelli, Alfonso Bueno-Orovio, Iacopo Olivotto and Mark V. Sherrid
(Top) In HCM cardiomyocytes, ICa-L and INaL are increased, while IK is markedly decreased, leading to prolonged APs; Na overload impairs NCX, contributing to cytosolic Ca-overload. (Bottom) Disopyramide inhibits INa-peak (INaP), INaL, ICa-L and IK, while also stabilizing ryanodine receptors. These effects lead to shortening of APs. Moreover, normalization of NCX function and ICa-L inhibition and RyR stabilization contribute to reduce diastolic Ca and systolic Ca-release, determining negative inotropic effects.
APs = action potentials; HCM = hypertrophic cardiomyopathy; ICa-L = L-type Ca current; IK = delayed-rectifier K current; INaL = Late Na current; NCX = Na+/Ca2+ exchanger; RyR = ryanodine receptor.