標題: Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts
作者: Yin, Dechun
Hsieh, Yu-Cheng
Tsai, Wei-Chung
Wu, Adonis Zhi-Yang
Jiang, Zhaolei
Chan, Yi-Hsin
Xu, Dongzhu
Yang, Na
Shen, Changyu
Chen, Zhenhui
Lin, Shien-Fong
Chen, Peng-Sheng
Everett, Thomas H.
分子醫學與生物工程研究所
Institute of Molecular Medicine and Bioengineering
關鍵字: apamin;electrophysiology;heart failure;potassium;ventricular fibrillation
公開日期: 1-二月-2017
摘要: Background-Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents (I-KAS) are heterogeneously upregulated in failing hearts. We hypothesized that I-KAS influences the location and stability of rotors during VF. Methods and Results-Optical mapping was performed on 9 rabbit hearts with pacing-induced heart failure. The epicardial right ventricular and left ventricular surfaces were simultaneously mapped in a Langendorff preparation. At baseline and after apamin (100 nmol/L) infusion, the action potential duration (APD(80)) was determined, and VF was induced. Areas with a >50% increase in the maximum action potential duration (Delta APD) after apamin infusion were considered to have a high I-KAS distribution. At baseline, the distribution density of phase singularities during VF in high I-KAS distribution areas was higher than in other areas (0.0035 +/- 0.0011 versus 0.0014 +/- 0.0010 phase singularities/pixel; P=0.004). In addition, high dominant frequencies also colocalized to high I-KAS distribution areas (26.0 versus 17.9 Hz; P=0.003). These correlations were eliminated during VF after apamin infusion, as the number of phase singularities (17.2 versus 11.0; P=0.009) and dominant frequencies (22.1 versus 16.2 Hz; P=0.022) were all significantly decreased. In addition, reentrant spiral waves became unstable after apamin infusion, and the duration of VF decreased. Conclusions-The I-KAS current influences the mechanism of VF in failing hearts as phase singularities, high dominant frequencies, and reentrant spiral waves all correlated to areas of high I-KAS. Apamin eliminated this relationship and reduced VF vulnerability.
URI: http://dx.doi.org/10.1161/CIRCEP.116.004434
http://hdl.handle.net/11536/146127
ISSN: 1941-3149
DOI: 10.1161/CIRCEP.116.004434
期刊: CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
Volume: 10
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