Related Experiment Video
Updated: Sep 3, 2025
Impact of Intracardiac Neurons on Cardiac Electrophysiology and Arrhythmogenesis in an Ex Vivo Langendorff System
Published on: May 22, 2018
Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in
Xiuming Dong1, Gary Tse2,3,4, Guoliang Hao1,5
1Henan SCOPE Research Institute of Electrophysiology Co., Ltd., Kaifeng 475000, China.
Insights
Heptanol, a gap junction and sodium channel inhibitor, slows ventricular conduction and alters propagation patterns, contributing to arrhythmias in mouse hearts. This study reveals how heptanol affects heart rate and activation latencies, providing insights into arrhythmogenesis.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Pharmacology
Background:
- Previous studies linked heptanol, a gap junction and sodium channel inhibitor, to slowed ventricular conduction and arrhythmogenesis in mouse hearts.
- These studies did not fully elucidate the specific propagation patterns contributing to the arrhythmogenic substrate.
- This research investigates conduction abnormalities induced by heptanol using advanced mapping techniques.
Purpose of the Study:
- To investigate the effects of heptanol on ventricular conduction patterns and arrhythmogenesis in mouse hearts.
- To characterize changes in activation latencies and conduction velocity using multi-electrode array mapping.
- To determine the relationship between heptanol-induced conduction abnormalities and the development of ventricular arrhythmias.
Main Methods:
- Langendorff-perfused mouse hearts were used, exposed to 0.1 mM or 2 mM heptanol.
- Multi-electrode array mapping was performed on the left ventricular epicardium.
- Recordings were obtained during spontaneous beating and during right ventricular pacing (8 Hz or S1S2 protocols).
Main Results:
- Heptanol significantly reduced heart rate and increased mean activation latencies and their variability during pacing.
- Conduction velocity was reduced, evidenced by increased P50 and P95 values.
- Absolute inhomogeneity in conduction (P5-95) increased, while the inhomogeneity index (P5-95/P50) showed a significant reduction.
Conclusions:
- Heptanol induces significant alterations in ventricular conduction, including slowed conduction and increased activation latency variability.
- These conduction abnormalities, characterized by increased inhomogeneity, are associated with both spontaneous and induced ventricular arrhythmias.
- The findings highlight the role of gap junction and sodium channel inhibition by heptanol in creating an arrhythmogenic substrate in the heart.
Abstract:
Background: Previous studies have associated slowed ventricular conduction with the arrhythmogenesis mediated by the gap junction and sodium channel inhibitor heptanol in mouse hearts. However, they 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: Recordings were made from the left ventricular epicardium using multi-electrode arrays in spontaneously beating hearts during right ventricular 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, the 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 the 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 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 the increased inhomogeneity index of conduction were associated with both spontaneous and induced ventricular arrhythmias.
