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
(A) Representative intracellular Ca2+ traces recorded during regular stimulation at 0.2, 0.5, and 1 Hz, in the absence (left, black) and presence of disopyramide 5 μmol/l (Diso) (blue traces on the right). (B) Percentage of variation of diastolic [Ca2+]i, and Ca-transient amplitude (Systolic Ampl) with the application of disopyramide 5 μmol/l with respect to baseline in hypertrophic cardiomyopathy cardiomyocytes, during regular stimulation at 0.2, 0.5, and 1 Hz at steady state. (C) Representative superimposed action potentials (top) and simultaneously recorded Ca transients (bottom) at baseline (black traces) and in the presence of disopyramide (blue traces), elicited at 0.2 Hz (left) and 0.5 Hz (right). (D) Time from peak to 50% decay of Ca transients at baseline (black) and in the presence of disopyramide 5 μmol/l (blue), elicited at 0.2, 0.5, and 1 Hz. (B–D) Means ± SEM from 26 cardiomyocytes from 7 patients with hypertrophic cardiomyopathy (ID 5 to 9 and 11 to 13). *0.05 > p > 0.01; **0.01 > p > 0.001; linear-mixed models. MP = membrane potential.