Masonic Medical Research Laboratory, Utica, New York 13501, USA.
J Cardiovasc Electrophysiol. 2010 Apr;21(4):441-7. doi: 10.1111/j.1540-8167.2009.01641.x. Epub 2009 Nov 10.
This study was designed to quantitate transseptal dispersion of repolarization (DR) and delineate its role in arrhythmogenesis using the calcium agonist BayK 8644 to mimic the gain of function of calcium channel current responsible for Timothy syndrome.
Amplification of transmural dispersion of repolarization (TDR) has been shown to contribute to development of Torsade de Pointes (TdP) arrhythmias under long-QT conditions.
An arterially perfused septal wedge preparation was developed via cannulation of the septal artery. Action potentials (APs) were recorded using floating microelectrodes together with a transseptal electrocardiogram (ECG). These data were compared to those recorded from arterially perfused canine left ventricular (LV) wedge preparations.
Under control conditions, the shortest AP duration measured at 90% repolarization (APD(90)) was observed in right ventricular (RV) endocardium (181.8 +/- 15 ms), APD(90) peaked close to midseptum (278.0 +/- 32 ms), and abbreviated again as LV endocardium was approached (207.3 +/- 9 ms). Transseptal DR averaged 106 +/- 24 ms and T(peak)-T(end) 84 +/- 7 ms (n = 6). TDR and T(peak)-T(end) recorded from LV wedge were 36 +/- 9 ms and 34 +/- 19 ms, respectively (n = 30). BayK 8644 increased transseptal DR to 123.2 +/- 35 ms (n = 5) and induced early and delayed afterdepolarizations (3/5), rate-dependent ST-T-wave alternans (5/5), and TdP arrhythmias (3/5).
Our data indicate that dispersion of repolarization across the interventricular septum is twice that of the LV free wall, predisposing to development of TdP under long-QT conditions. Our findings suggest that the coronary-perfused ventricular septal preparation may be a sensitive model in which to assess the potential arrhythmogenic effects of drugs and pathophysiological conditions.
本研究旨在通过钙激动剂 BayK 8644 模拟钙电流功能获得，定量测量跨室间隔复极离散（DR），并阐述其在心律失常发生中的作用，这种钙电流与 Timothy 综合征有关。
已有研究表明，复极跨壁离散度（TDR）的放大有助于长 QT 条件下尖端扭转型室性心动过速（TdP）心律失常的发展。
通过对间隔动脉进行插管，建立动脉灌注的间隔楔形切片制备。使用漂浮微电极与经间隔心电图（ECG）一起记录动作电位（AP）。将这些数据与动脉灌注的犬左心室（LV）楔形切片制备记录的数据进行比较。
在对照条件下，90%复极时最短的动作电位时程（APD90）在右心室（RV）心内膜处观察到（181.8 +/- 15 ms），APD90 在中隔附近达到峰值（278.0 +/- 32 ms），当接近 LV 心内膜时再次缩短（207.3 +/- 9 ms）。经间隔 DR 平均为 106 +/- 24 ms，T 峰-T 末为 84 +/- 7 ms（n = 6）。从 LV 楔形切片记录的 TDR 和 T 峰-T 末分别为 36 +/- 9 ms 和 34 +/- 19 ms（n = 30）。BayK 8644 将经间隔 DR 增加到 123.2 +/- 35 ms（n = 5），并诱导早期和延迟后除极（3/5）、速率依赖性 ST-T 波交替（5/5）和 TdP 心律失常（3/5）。
我们的数据表明，室间隔的复极离散度是 LV 游离壁的两倍，在长 QT 条件下易发生 TdP。我们的发现表明，冠状灌注的室间隔制备可能是一种敏感的模型，可以评估药物和病理生理条件的潜在致心律失常作用。
