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
Effects of Disopyramide in Myocardial Mechanics in Intact and Skinned Trabecuale
(A) Representative superimposed force twitches elicited at 0.5 Hz in hypertrophic cardiomyopathy (HCM) trabeculae in the absence (black trace) and presence (blue trace) of disopyramide 5 μmol/l (Diso). (B) Relationship between the negative inotropic effect of disopyramide and its concentration in the extracellular fluid; calculated concentration at which 50% of the maximal effect is obtained (EC50) is shown. Means ± SEM from 5 trabeculae, 5 patients. (C) Time from stimulus to peak and time from peak to 50% relaxation (RT50%) of force twitches elicited at 1 Hz at baseline (black) and in the presence of disopyramide (blue). (D) Effects of disopyramide at different stimulation frequencies. Disopyramide slightly reduces the slope of force-frequency relationship at higher pacing rates. (C,D) Means ± SEM from 13 trabeculae, 10 patients (ID 1, 2, and 5 to 12). (E) Disopyramide in skinned trabeculae from patients with HCM. As shown in these superimposed traces from an HCM trabecula, disopyramide does not reduce isometric force at intermediate Ca activation level (pCa 6) or at maximal myofilament activation (pCa 4.5). (F) Maximal tension and pCa at one-half of maximal tension (Ca sensitivity) in HCM trabeculae, in the absence and presence of disopyramide. Means ± SEM from 6 trabeculae, 3 patients (ID 12, 15, and 16). (C,D,F) *0.05 > p > 0.01; **0.01 > p > 0.001; ***p < 0.001; linear-mixed models. bpm = beats/min.