Key result
Heptanol prolongs activation latency ~180% and increases conduction inhomogeneity, promoting ventricular arrhythmias in mouse hearts.
Why the study?
Previous studies linked heptanol-mediated conduction slowing to arrhythmogenesis in mouse hearts, but did not study the propagation patterns contributing to the arrhythmic substrate.
Does heptanol alter ventricular conduction patterns and contribute to an arrhythmic substrate in Langendorff-perfused mouse hearts?
Does heptanol alter ventricular conduction patterns and contribute to an arrhythmic substrate in Langendorff-perfused mouse hearts?
Absolute Event Rate: 19.9% vs 7.1%
p-value: p=<0.05
Heptanol-induced gap junction and sodium channel inhibition slows ventricular conduction and increases conduction inhomogeneity, providing a substrate for ventricular arrhythmias in mouse hearts.
Heptanol promotes arrhythmogenic conduction slowing in isolated mouse hearts; hypothesis-generating for gap junction uncoupling but leaves open clinical translation.
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.
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Dong et al. (2022) studied Ventricular arrhythmias. Heptanol vs. Baseline (no heptanol) was evaluated on Mean local activation times (LATs) during 8 Hz pacing (p=<0.05). Heptanol at 0.1 and 2 mM increased mean activation latencies (from 7.1 to 19.9 and 18.4 ms; p<0.05) and conduction inhomogeneity, contributing to ventricular arrhythmias in mouse hearts.
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