Key result
High-dose ranolazine suppresses post-MI ventricular arrhythmias in rabbits while a lower dose aggravates them.
Why the study?
Ranolazine prevents ventricular arrhythmias during acute MI, but its efficacy on ventricular arrhythmias induced several days post-MI remained to be investigated.
Does ranolazine prevent reentrant ventricular arrhythmias induced after subacute myocardial infarction in a rabbit model?
Does ranolazine prevent reentrant ventricular arrhythmias induced after subacute myocardial infarction in a rabbit model?
High-dose ranolazine exerts antiarrhythmic efficacy against subacute-MI ventricular arrhythmias in rabbits, partly through VERP prolongation, whereas low-dose ranolazine may aggravate them.
Dose-dependent ranolazine effects on post-MI arrhythmias in rabbits are hypothesis-generating; clinical translation and optimal dosing remain open.
Ranolazine has been found to prevent ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study aimed to investigate its efficacy on VAs induced several days post-MI. For this purpose, 13 anesthetized rabbits underwent coronary artery ligation. Ten of these animals that survived AMI were reanesthetized 3 to 7 days later for electrophysiologic testing. An endocardial monophasic action potential combination catheter was placed in the right ventricle for simultaneous pacing and recording. Monophasic action potential duration, ventricular effective refractory period (VERP), and VAs induced by programmed stimulation were assessed. Measurements were performed during control pacing, and following an intravenous infusion of either a low-dose ranolazine (2.4 mg/kg, R1) or a higher dose ranolazine (4.8 mg/kg cumulative dose, R2). During control stimulation, 2 animals developed primary ventricular fibrillation (VF), 6 sustained ventricular tachycardia (sVT), and 2 nonsustained VT (nsVT). R1 did not prevent the appearance of VAs in any of the experiments; in contrast, it aggravated nsVT into sVT and complicated sVT termination in 2 of 6 animals. Sustained ventricular tachycardia cycle length and VERP were only slightly decreased after R1 (112 ± 5 vs 110 ± 6 ms and 101 ± 11 vs 98 ± 10 ms, respectively). R2 suppressed inducibility of control nsVT, VF, and sVT in 2 animals. In 4 animals with still inducible sVT, R2 significantly prolonged VT cycle length by 150 ± 23 ms ( P < .01), and VERP by 120 ± 7 ms ( P < .001) versus control. In conclusion, R2 exerted antiarrhythmic efficacy against subacute-MI VAs, whereas R1 rather aggravated than prevented these arrhythmias. Ventricular effective refractory period prolongation could partially explain the antiarrhythmic action of R2 in this rabbit model.
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Moschovidis et al. (2019) studied Subacute myocardial infarction with ventricular arrhythmias (n=10). Ranolazine vs. Control pacing (baseline) was evaluated on Ventricular arrhythmias induced by programmed stimulation, VT cycle length, and ventricular effective refractory period. Higher dose ranolazine (4.8 mg/kg) suppressed or prolonged the cycle length of induced ventricular arrhythmias post-MI in rabbits, whereas a lower dose (2.4 mg/kg) aggravated them.
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