Atrial anti-arrhythmic effects of heptanol in Langendorff-perfused mouse hearts
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Acute effects of heptanol (0.1 to 2 mM) on atrial electrophysiology were explored in Langendorff-perfused mouse hearts. Left atrial bipolar electrogram or monophasic action potential recordings were obtained during right atrial stimulation. Regular pacing at 8 Hz elicited atrial activity in 11 out of 11 hearts without inducing atrial arrhythmias. Programmed electrical stimulation using a S1S2 protocol provoked atrial tachy-arrhythmias in 9 of 17 hearts. In the initially arrhythmic group, 2 mM heptanol exerted anti-arrhythmic effects (Fisher’s exact test, P < 0.05) and increased atrial effective refractory period (ERP) from 26.0 ± 1.9 to 57.1 ± 2.5 ms (ANOVA, P < 0.001) despite reducing CV 0.17 ± 0.01 to 0.11 ± 0.01 m/s (P < 0.01) and leaving action potential duration at 90% repolarization (APD₉₀) unaltered (25.6 ± 1.2 vs. 27.2 ± 1.2 ms; P > 0.05), which led to increases in excitation wavelength (CV x ERP) from 4.3 ± 0.4 to 6.2 ± 0.5 mm (P < 0.01), and ERP/APD₉₀ ratio from 1.0 ± 0.1 to 2.1 ± 0.2 (P < 0.001). In contrast, in the initially non-arrhythmic group, heptanol did not alter arrhythmogenicity, increased AERP from 47.3 ± 5.3 to 54.5 ± 3.1 ms (P < 0.05), reduced CV from 0.13 ± 0.01 to 0.10 ± 0.01 m/s (P < 0.05) and did not alter APD₉₀ (24.1 ± 1.2 vs. 25.0 ± 2.3 ms; P > 0.05), leaving both excitation wavelength (6.3 ± 0.9 vs. 5.6 ± 0.6; P > 0.05) and ERP/APD₉₀ ratio (2.0 ± 0.2 vs. 2.1 ± 0.1; P > 0.05) unaltered. Lower heptanol concentrations (0.1, 0.5 and 1 mM) did not alter arrhythmogenicity or the above parameters. The present findings contrast with known ventricular pro-arrhythmic effects of heptanol associated with decreased ventricular wavelength, despite increased ERP/APD ratio observed in both the atria and ventricles.
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This is the author accepted manuscript. It is currently embargoed pending publication.
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1932-6203