Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts
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...
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MDPI AG
2022-07-01
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| Online Access: | https://www.mdpi.com/2075-1729/12/7/996 |
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| author | Xiuming Dong Gary Tse Guoliang Hao Yimei Du |
| author_facet | Xiuming Dong Gary Tse Guoliang Hao Yimei Du |
| author_sort | Xiuming Dong |
| collection | DOAJ |
| description | 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, <i>p</i> < 0.05 and <i>p</i> < 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 (<i>p</i> < 0.05) and 18.4 ± 5.7 ms (<i>p</i> < 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 (<i>p</i> < 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 (<i>p</i> < 0.05). P<sub>5</sub> 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, <i>p</i> > 0.05). P<sub>50</sub> 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 (<i>p</i> < 0.05). P<sub>95</sub> 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 (<i>p</i> < 0.05). These changes led to increases in the absolute inhomogeneity in conduction (P<sub>5–95</sub>) from 7.1 ± 2.6 ms to 31.4 ± 11.3 ms, 2 mM: 21.6 ± 7.2 ms, respectively (<i>p</i> < 0.05). The inhomogeneity index (P<sub>5–95</sub>/P<sub>50</sub>) 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 (<i>p</i> < 0.05). Conclusion: Increased activation latencies, reduced CVs, and the increased inhomogeneity index of conduction were associated with both spontaneous and induced ventricular arrhythmias. |
| first_indexed | 2024-03-09T13:31:10Z |
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| publishDate | 2022-07-01 |
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| series | Life |
| spelling | doaj.art-69b4e5b0d0c34efcb37bd32e857ab4802023-11-30T21:17:55ZengMDPI AGLife2075-17292022-07-0112799610.3390/life12070996Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse HeartsXiuming Dong0Gary Tse1Guoliang Hao2Yimei Du3Henan SCOPE Research Institute of Electrophysiology Co., Ltd., Kaifeng 475000, ChinaCardiac Electrophysiology Unit, Cardiovascular Analytics Group, Hong Kong, ChinaHenan SCOPE Research Institute of Electrophysiology Co., Ltd., Kaifeng 475000, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaBackground: 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, <i>p</i> < 0.05 and <i>p</i> < 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 (<i>p</i> < 0.05) and 18.4 ± 5.7 ms (<i>p</i> < 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 (<i>p</i> < 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 (<i>p</i> < 0.05). P<sub>5</sub> 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, <i>p</i> > 0.05). P<sub>50</sub> 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 (<i>p</i> < 0.05). P<sub>95</sub> 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 (<i>p</i> < 0.05). These changes led to increases in the absolute inhomogeneity in conduction (P<sub>5–95</sub>) from 7.1 ± 2.6 ms to 31.4 ± 11.3 ms, 2 mM: 21.6 ± 7.2 ms, respectively (<i>p</i> < 0.05). The inhomogeneity index (P<sub>5–95</sub>/P<sub>50</sub>) 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 (<i>p</i> < 0.05). Conclusion: Increased activation latencies, reduced CVs, and the increased inhomogeneity index of conduction were associated with both spontaneous and induced ventricular arrhythmias.https://www.mdpi.com/2075-1729/12/7/996action potential durationvariabilityentropydetrended fluctuation analysishypokalemiaconduction |
| spellingShingle | Xiuming Dong Gary Tse Guoliang Hao Yimei Du Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts Life action potential duration variability entropy detrended fluctuation analysis hypokalemia conduction |
| title | Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts |
| title_full | Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts |
| title_fullStr | Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts |
| title_full_unstemmed | Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts |
| title_short | Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts |
| title_sort | heterogeneities in ventricular conduction following treatment with heptanol a multi electrode array study in langendorff perfused mouse hearts |
| topic | action potential duration variability entropy detrended fluctuation analysis hypokalemia conduction |
| url | https://www.mdpi.com/2075-1729/12/7/996 |
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