Key result
Flecainide and quinidine significantly increased the maximum slope of excitation wavelength restitution, whereas lidocaine and mexiletine reduced it, explaining their differing arrhythmic safety profiles.
Why the study?
Do different classes of Na+ channel blockers produce contrasting effects on the rate adaptation of the excitation wavelength in perfused guinea-pig hearts?
Do different classes of Na+ channel blockers produce contrasting effects on the rate adaptation of the excitation wavelength in perfused guinea-pig hearts?
Class Ia and Ic Na+ channel blockers steepen the excitation wavelength restitution due to use-dependent conduction slowing, whereas class Ib agents flatten it, providing a mechanistic explanation for their differing proarrhythmic and antiarrhythmic profiles.
Differential restitution effects in guinea-pig hearts leave open whether class-specific Na+ blockade alters human arrhythmia risk; hypothesis-generating for targeted trials.
Na+ channel blockers flecainide and quinidine can increase propensity to ventricular tachyarrhythmia, whereas lidocaine and mexiletine are recognized as safe antiarrhythmics. Clinically, ventricular fibrillation is often precipitated by transient tachycardia that reduces action potential duration, suggesting that a critical shortening of the excitation wavelength (EW) may contribute to the arrhythmic substrate. This study examined whether different INa blockers can produce contrasting effects on the rate adaptation of the EW, which would explain the difference in their safety profile. In perfused guinea-pig hearts, effective refractory periods (ERP), conduction times, and EW values were determined over a wide range of cardiac pacing intervals. All INa blockers tested were found to flatten the slope of ERP restitution, indicating antiarrhythmic tendency. However, with flecainide and quinidine, the beneficial changes in ERP were reversed owing to the use-dependent conduction slowing, thereby leading to significantly steepened restitution of the EW. In contrast, lidocaine and mexiletine had no effect on ventricular conduction, and therefore reduced the slope of the EW restitution, as expected from their effect on ERP. These findings suggest that the slope of the EW restitution is an important electrophysiological determinant which can discriminate INa blockers with proarrhythmic and antiarrhythmic profile.
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Oleg E. Osadchii (2017) studied this question. Flecainide, quinidine, lidocaine, and mexiletine vs. Baseline was evaluated on Maximum slope of excitation wavelength restitution. Flecainide and quinidine significantly increased the maximum slope of excitation wavelength restitution, whereas lidocaine and mexiletine reduced it, explaining their differing arrhythmic safety profiles.
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