| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2962812 | Journal of Cardiology | 2015 | 8 Pages |
BackgroundNa+/Ca2+ exchanger blockade has been reported to be anti-arrhythmic in different models. The effects of KB-R7943, a Na+/Ca2+ exchanger blocker, on arrhythmogenesis in hearts with chronic myocardial infarction (MI) remain unclear.MethodsDual voltage and intracellular Ca2+ (Cai) optical mapping was performed in nine rabbit hearts with chronic MI and four control hearts. Electrophysiology studies including inducibility of ventricular tachyarrhythmias, ventricular fibrillation dominant frequency, action potential, Cai alternans, Cai decay, and conduction velocity were performed. The same protocol was repeated in the presence of KB-R7943 (0.5, 1, and 5 μM) after the baseline studies.ResultsKB-R7943 was effective in suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias in hearts with chronic MI. Surprisingly, KB-R7943 increased the inducibility of ventricular tachyarrhythmias in a dose-dependent manner (11%, 11%, 22%, and 56% at baseline and with 0.5, 1, and 5 μM KB-R7943, respectively, p = 0.02). Optical mapping analysis revealed that the underlying mechanisms of the induced ventricular tachyarrhythmias were probably spatially discordant alternans with wave breaks and rotors. Further analysis showed that KB-R7943 significantly enhanced both action potential (p = 0.033) and Cai (p = 0.001) alternans, prolonged Cai decay (tau value) in a dose-dependent manner (p = 0.004), and caused heterogeneous conduction delay especially at peri-infarct zones during rapid burst pacing. In contrast, KB-R7943 had insignificant effects in control hearts.ConclusionsIn this chronic MI rabbit model, KB-R7943 has contrasting effects on arrhythmogenesis, suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias, but enhancing the inducibility of tachyarrhythmias. The mechanism is probably the enhanced spatially discordant alternans because of prolonged Cai decay and heterogeneous conduction delay.
