Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.
Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.
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DOI：
10.1161/circep.116.004434
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Everett TH 4th
中科院分区：
文献类型：
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作者：
Yin D;Hsieh YC;Tsai WC;Wu AZ;Jiang Z;Chan YH;Xu D;Yang N;Shen C;Chen Z;Lin SF;Chen PS;Everett TH 4th
心力衰竭期间的心室颤动（VF）以稳定的折返螺旋波（转子）为特征。Apamin敏感的小电导钙激活钾电流（IKAS）在衰竭心脏中不均匀上调。我们假设IKAS影响VF期间转子的位置和稳定性。对9只兔起搏性心力衰竭心脏进行光学标测。心外膜RV和LV在Langendorff准备中同时标测。在基线和注射apamin（100 nmol/L）后，测定APD 80并诱导VF。接受apamin后，最大APD（ΔAPD）增加超过50%的区域被认为具有高IKAS分布。基线时，高IKAS分布区VF期间相位奇点（PS）的分布密度高于其他区域（0.0035± 0.0011 vs 0.0014±0.0010 PS/像素，P=0.004）。此外，高主频（DF）也共同定位于高IKAS分布区（26.0 vs 17.9 Hz，P=0.003）。这些相关性在注射apamin后的VF期间被消除，因为PS（17.2 vs 11.0，P=0.009）和DF（22.1 vs 16.2 Hz，P=0.022）的数量均显著减少。此外，注射apamin后，折返螺旋波变得不稳定，VF持续时间缩短。IKAS电流影响衰竭心脏中VF的机制，因为PS、高DF和折返螺旋波都与高IKAS区域相关。Apamin消除了这种关系，降低了VF的脆弱性。
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 up-regulated 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 RV and LV were simultaneously mapped in a Langendorff preparation. At baseline and after apamin (100 nmol/L) infusion, the APD80 was determined and VF was induced. Areas with a greater than 50% increase in the maximum APD (ΔAPD) after apamin were considered to have a high IKAS distribution. At baseline, the distribution density of phase singularities (PS) during VF in high IKAS distribution areas was higher than in other areas (0.0035±.0011 vs 0.0014±0.0010 PS/pixel, P=0.004). In addition, high dominant frequencies (DF) also co-localized to high IKAS distribution areas (26.0 vs 17.9 Hz, P=0.003). These correlations were eliminated during VF after apamin infusion, as the number of PS (17.2 versus 11.0, P=0.009), and DFs (22.1 vs 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 PS, high DFs, and reentrant spiral waves all correlated to areas of high IKAS. Apamin eliminated this relationship and reduced VF vulnerability.