Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Dóm tér 12, P.O. Box 427, 6720, Szeged, Hungary.
ELKH-SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary.
Sci Rep. 2021 Aug 17;11(1):16652. doi: 10.1038/s41598-021-95299-7.
Cardiac alternans have crucial importance in the onset of ventricular fibrillation. The early explanation for alternans development was the voltage-driven mechanism, where the action potential (AP) restitution steepness was considered as crucial determining factor. Recent results suggest that restitution slope is an inadequate predictor for alternans development, but several studies still claim the role of membrane potential as underlying mechanism of alternans. These controversial data indicate that the relationship of restitution and alternans development is not completely understood. APs were measured by conventional microelectrode technique from canine right ventricular papillary muscles. Ionic currents combined with fluorescent measurements were recorded by patch-clamp technique. APs combined with fluorescent measurements were monitored by sharp microelectrodes. Rapid pacing evoked restitution-independent AP duration (APD) alternans. When non-alternating AP voltage command was used, Ca-transient (CaT) alternans were not observed. When alternating rectangular voltage pulses were applied, CaT alternans were proportional to I amplitude alternans. Selective I inhibition did not influence the fast phase of APD restitution. In this study we found that I has minor contribution in shaping the fast phase of restitution curve suggesting that I-if it plays important role in the alternans mechanism-could be an additional factor that attenuates the reliability of APD restitution slope to predict alternans.
心脏交替在室颤的发生中具有至关重要的意义。早期对交替发生发展的解释是电压驱动机制，其中动作电位（AP）复极斜率被认为是关键的决定因素。最近的结果表明，复极斜率不能充分预测交替的发生，但仍有几项研究声称膜电位是交替发生的潜在机制。这些有争议的数据表明，复极与交替发生发展之间的关系尚未完全阐明。采用传统的微电极技术从犬右心室乳头肌测量 AP。采用膜片钳技术结合荧光测量记录离子电流。采用锐利微电极监测 AP 与荧光测量。快速起搏引发与复极无关的 AP 持续时间（APD）交替。当使用非交替 AP 电压指令时，未观察到 Ca 瞬变（CaT）交替。当施加交替矩形电压脉冲时，CaT 交替与 I 幅度交替成正比。选择性 I 抑制对 APD 复极的快速相没有影响。在这项研究中，我们发现 I 在塑造复极曲线的快速相方面贡献较小，这表明 I（如果它在交替机制中发挥重要作用）可能是一个附加因素，会降低 APD 复极斜率预测交替的可靠性。
