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SD3212, a new antiarrhythmic drug, raises atrial fibrillation threshold in isolated rabbit hearts

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Summary

SD3212 is a new antiarrhythmic drug which has class I, III, and IV effects. The purpose of this study was to elucidate the electrophysiological effects of this compound on a rabbit atrial fibrillation model, and to test a hypothesis that atrial fibrillation threshold is a quantitative indicator of atrial vulnerability. Whole hearts were excised from rabbits, and the aortas cannulated to perfuse the coronary arteries. Atrial fibrillation was induced with a burst stimulation of 50 Hz for 1 s while 3µM acetylcholine (ACh) was perfused. When the right atrial appendage was paced at 200-ms intervals, SD3212 prolonged interatrial conduction time: control 30 ± 1.2ms, ACh 33 ± 1.4ms, ACh + SD 1µM 37 ± 2.4ms, ACh + SD 3µM 52 ± 8.1ms. The drug also prolonged the effective refractory period: control 80 ± 3.0ms, ACh 48 ± 3.8ms, ACh + SD 1µM 65 ± 4.7ms, ACh + SD 3 µM 98 ± 15ms. The rate of induction of atrial fibrillation by rapid pacing was 26% in Tyrode's solution, 85% in the presence of ACh, and 38% in the presence of ACh + SD 1 µM. The atrial fibrillation threshold decreased from 8.6 ± 0.8 mA (control) to 2.5 ± 0.7 mA in the presence of ACh. It increased again to 7.8 ± 1.0 mA in the presence of SD3212 (1 µM). SD3212 prolonged both the conduction time and refractory period. A reversed use-dependency was not prominent. These features caused antifibrillatory effects. Thus, the atrial fibrillation threshold seems to be a good quantitative indicator of atrial vulnerability.

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Authors and Affiliations

  1. Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamigyo-ku, 602-8566, Kyoto, Japan

    Ryohei Matsuo, Takeshi Shirayama, Keiji Inoue, Yayoi Matoba, Hiroto Imai, Hirokazu Shiraishi, Tetsuya Tatsumi & Masao Nakagawa

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  1. Ryohei Matsuo
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  2. Takeshi Shirayama
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  3. Keiji Inoue
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  4. Yayoi Matoba
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  5. Hiroto Imai
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  6. Hirokazu Shiraishi
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  7. Tetsuya Tatsumi
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  8. Masao Nakagawa
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Matsuo, R., Shirayama, T., Inoue, K. et al. SD3212, a new antiarrhythmic drug, raises atrial fibrillation threshold in isolated rabbit hearts. Heart Vessels 14, 127–136 (1999). https://doi.org/10.1007/BF02482296

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  • DOI: https://doi.org/10.1007/BF02482296

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