Masonic Medical Research Laboratory, Utica, NY, USA.
Heart Rhythm. 2010;7(2):251-7. doi: 10.1016/j.hrthm.2009.10.017. Epub 2009 Oct 17.
Short QT (SQT) syndrome (SQT) 1 is an inherited sudden death syndrome often associated with atrial fibrillation (AF). We examined the cellular basis for AF in a newly developed experimental atrial model of SQT1.
Action potentials (APs) were recorded from the pectinate muscle (PM) and crista terminalis (CT) regions of coronary-perfused canine right atrial preparations, together with a pseudoelectrocardiogram. The I(Kr) agonist PD-118057 (20 microM) was used to mimic the gain of function in I(Kr) known to underlie SQT1.
The I(Kr) agonist significantly abbreviated the AP duration (APD) of CT and PM and of the effective refractory period (ERP) measured in PM (n = 28). Spatial dispersion of repolarization (SDR), defined as inter-regional differences of APD, increased from 27 +/- 17 ms to 51 +/- 32 ms (P = .002; n = 28). AF could be induced by a single premature stimulus after but not before exposure to PD-118057 in 26/28 (93%) preparations. Quinidine (10 microM), which prolonged APD and ERP, but not lidocaine (20 microM) or E-4031 (5 microM), which prolonged only ERP or APD, respectively, was effective in preventing the PD-118057-mediated AF. In the presence of PD-118057, isoproterenol (100 nM) further abbreviated both APD and ERP and facilitated induction of sustained AF in five of six preparations.
The I(Kr) agonist recapitulates the electrophysiologic and arrhythmic manifestations of SQT1. Abbreviation of APD and ERP and amplification of SDR predispose to the development of AF by creating the substrate for reentry. Quinidine, but not E-4031 or lidocaine, was effective in preventing AF in this setting.
短 QT（SQT）综合征（SQT）1 是一种遗传性猝死综合征，常与心房颤动（AF）相关。我们在新开发的 SQT1 实验性心房模型中检查了 AF 的细胞基础。
从冠状灌注犬右心房标本的梳状肌（PM）和终嵴区域记录动作电位（AP），并伴有伪心电图。使用 I（Kr）激动剂 PD-118057（20 μM）模拟已知导致 SQT1 的 I（Kr）功能获得。
I（Kr）激动剂显著缩短 CT 和 PM 的 AP 持续时间（APD）和 PM 中测量的有效不应期（ERP）（n = 28）。复极离散度（SDR），定义为 APD 的区域间差异，从 27 ± 17 ms 增加到 51 ± 32 ms（P =.002；n = 28）。在 PD-118057 暴露后而非暴露前，可通过单个过早刺激诱导 28/28（93%）标本中的 AF。奎尼丁（10 μM）可延长 APD 和 ERP，但利多卡因（20 μM）或 E-4031（5 μM）不能延长 ERP 或 APD，分别延长 ERP 或 APD，可有效预防 PD-118057 介导的 AF。在 PD-118057 存在下，异丙肾上腺素（100 nM）进一步缩短 APD 和 ERP，并促进五分之六标本中持续性 AF 的诱导。
I（Kr）激动剂再现了 SQT1 的电生理和心律失常表现。APD 和 ERP 的缩短以及 SDR 的放大为折返的发展提供了诱发 AF 的基质。奎尼丁，而不是 E-4031 或利多卡因，在这种情况下有效预防 AF。
