Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.

Dechun Yin, Yu-Cheng Hsieh, Wei-Chung Tsai, Adonis Zhi-Yang Wu, Zhaolei Jiang, Yi-Hsin Chan, Dongzhu Xu, Na Yang, Changyu Shen, Zhenhui Chen, Shien-Fong Lin, Peng-Sheng Chen, Thomas H Everett

Circulation. Arrhythmia and electrophysiology 2017 Feb

filter terms:

Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents (IKAS) are heterogeneously upregulated in failing hearts. We hypothesized that IKAS influences the location and stability of rotors during VF. 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 (APD80) was determined, and VF was induced. Areas with a >50% increase in the maximum action potential duration (ΔAPD) after apamin infusion were considered to have a high IKAS distribution. At baseline, the distribution density of phase singularities during VF in high IKAS 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 IKAS 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. The IKAS 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 IKAS. Apamin eliminated this relationship and reduced VF vulnerability. © 2017 American Heart Association, Inc.

Citation

Dechun Yin, Yu-Cheng Hsieh, Wei-Chung Tsai, Adonis Zhi-Yang Wu, Zhaolei Jiang, Yi-Hsin Chan, Dongzhu Xu, Na Yang, Changyu Shen, Zhenhui Chen, Shien-Fong Lin, Peng-Sheng Chen, Thomas H Everett. Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts. Circulation. Arrhythmia and electrophysiology. 2017 Feb;10(2):e004434