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, left) Representative peak Na current traces elicited at −10 mV from −120 mV resting potential, in a hypertrophic cardiomyopathy cardiomyocyte in the absence (black) and presence of disopyramide (Diso) (blue trace). (Right) Average peak Na+ current (INa-peak) density at −10 mV; effect of disopyramide. (B, left) Representative late Na+ current (INaL) traces elicited at -10 mV from −120 mV resting potential, in the absence and presence of disopyramide. (Right) Average integral of the area of the current between 50 and 750 ms after onset of the −10 mV clamp pulse, normalized by cell capacitance, calculated in the absence and presence of disopyramide in hypertrophic cardiomyopathy cardiomyocytes. (A,B) Means ± SEM from 22 cardiomyocytes, 5 patients (ID 14 to 18). *0.05 > p > 0.01; **0.01 > p > 0.001; linear-mixed models. (C) Delayed-rectifier K currents (IK) elicited at different voltages in hypertrophic cardiomyopathy cardiomyocytes (see inset for color codes), in the absence of disopyramide (left) and in its presence (right). (D) Average IK current density in the absence and presence of disopyramide at different voltages. Mean ± SEM from 10 cardiomyocytes, 4 patients (ID 14, 16, 19, and 20). ‡p < 0.05 for voltages ≥+20 mV, linear-mixed models used to compare each coupled pair of values. (E) Representative L-type Ca2+ current (ICa-L) traces elicited at 0 mV from −80 mV resting voltage. (F) Average ICa-L current density in the absence and presence of disopyramide at different voltages. Mean ± SEM from 12 cardiomyocytes, 3 patients (ID 15, 17, and 18). §p < 0.05 for voltages between −10 mV and +30 mV, linear-mixed models.