Abstract
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 increasing activation latency from 18.7 ± 1.1 to 28.9 ± 2.1 ms (P < 0.001) 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 ERP/latency ratio from 1.4 ± 0.1 to 2.1 ± 0.2 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) and activation latency from 23.7 ± 2.2 to 31.3 ± 2.5 ms and did not alter APD90 (24.1 ± 1.2 vs. 25.0 ± 2.3 ms; P > 0.05), leaving both AERP/latency ratio (2.1 ± 0.3 vs. 1.9 ± 0.2; 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 ERP/latency ratio, despite increased ERP/APD ratio observed in both the atria and ventricles.
Highlights
The accurately timed sequence of contractile activity in different cardiac regions depends on the orderly generation and the subsequent propagation of an action potential (AP)
The present experiments investigated the effects of the gap junction and sodium channel inhibitor heptanol (0.1, 0.5, 1 or 2 mM) on atrial arrhythmic and electrophysiological properties in Langendorff-perfused mouse hearts, complementing a previous report describing its ventricular pro-arrhythmic effects [10]
Signals from atrial events were identified by deflections present in the Bipolar electrograms (BEGs) but absent from the Monophasic action potentials (MAPs) recordings, whereas those from ventricular events were identified by deflections present in both the BEG and MAP recordings
Summary
The accurately timed sequence of contractile activity in different cardiac regions depends on the orderly generation and the subsequent propagation of an action potential (AP). Conduction velocity (CV) of the AP depends on sodium channel activation followed by gap junction conduction through successive myocardial regions [1,2,3]. Decreases in CV, which is proportional to activation latency, have been associated with increased risk of arrhythmias [4, 5]. Cardiac arrhythmias have been explored in murine models, which permit alterations in the PLOS ONE | DOI:10.1371/journal.pone.0148858. Heptanol Exerts Anti-Arrhythmic Effects in the Mouse Atria up. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
