Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts

Version 1 : Received: 5 May 2022 / Approved: 11 May 2022 / Online: 11 May 2022 (13:08:36 CEST)

How to cite: Dong, X.; Tse, G.; Hao, G.; Du, Y. Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts. Preprints 2022, 2022050153 (doi: 10.20944/preprints202205.0153.v1). Dong, X.; Tse, G.; Hao, G.; Du, Y. Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts. Preprints 2022, 2022050153 (doi: 10.20944/preprints202205.0153.v1).

Abstract

Background: Previous studies have associated slowed ventricular conduction in the arrhythmogenesis mediated by the gap junction and sodium channel inhibitor heptanol in mouse hearts but did not study the propagation patterns that might contribute to the arrhythmic substrate. This study used a multi-electrode array mapping technique, to further investigate different conduction abnormalities in Langendorff-perfused mouse hearts exposed to 0.1 or 2 mM heptanol. Methods: Multi-electrode array recordings were made from the left ventricular epicardium in spontaneously beating hearts, during right ventricular regular 8 Hz pacing or S1S2 pacing. Results: In spontaneously beating hearts, heptanol at 0.1 and 2 mM significantly reduced the heart rate from 314±25 to 189±24 and 157±7 bpm, respectively (ANOVA, P<0.05 and P<0.001). During regular 8 Hz pacing, Mean LATs were increased by 0.1 and 2 mM heptanol from 7.1±2.2 ms to 19.9±5.0 ms (P<0.05) and 18.4±5.7 ms (P<0.05). The standard deviation of mean LATs was increased from 2.5±0.8 ms to 10.3±4.0 ms and 8.0±2.5 ms (P< 0.05), and the median of phase differences was significantly increased from 1.7±1.1 ms to 13.9±7.8 ms and 12.1±5.0 ms by 0.1 and 2 mM heptanol (P<0.05). P5 took a value of 0.2±0.1 ms and was not significantly altered by heptanol at 0.1 or 2 mM (1.1±0.9 ms and 0.9±0.5 ms, P>0.05). P50 was increased from 7.3±2.7 ms to 24.0±12.0 ms by 0.1 mM heptanol and then to 22.5±7.5 ms by 2 mM heptanol (P< 0.05). P95 was increased from 1.7±1.1 ms to 13.9±7.8 ms by 0.1 mM heptanol and to 12.1±5.0 ms by 2 mM heptanol (P<0.05). These changes led to increases in the absolute inhomogeneity in conduction (P5-95) from 7.1±2.6 ms to 31.4±11.3 ms, 2 mM: 21.6±7.2 ms, respectively (P<0.05). The inhomogeneity index (P5-95/P50) was significantly reduced from 3.7±1.2 to 3.1±0.8 by 0.1 mM and then to 3.3±0.9 by 2 mM heptanol (P<0.05). Conclusion: Increased activation latencies, reduced CVs and increased dispersion index of conduction were associated with both spontaneous and induced ventricular arrhythmias.

Keywords

conduction; heterogeneity; inhomogeneity; dispersion; mouse; heptanol

Subject

BIOLOGY, Physiology

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