中文摘要：

目的观察钙调蛋白激酶Ⅱ抑制剂KN-93对心肌肥厚兔室性心律失常的影响。方法雌性新西兰大白兔随机分为4组：假手术组（Sham组）、心肌肥厚组（LVH组）、心肌肥厚＋KN-93组（KN-93组）、心肌肥厚＋KN-92组（KN-92组），每组10只。LVH、KN-93及KN-92组通过缩窄腹主动脉制备兔心肌肥厚模型，Sham组仅游离腹主动脉未进行缩窄。8周后制备兔左室楔形心肌块的灌注模型，同步记录心内、外膜动作电位及跨壁心电图，观察低钾（2mmol／L）、低镁（0．25mmol／L）台氏液灌流及慢频率刺激条件下各组早期后除极（EAD）和尖端扭转型室性心动过速（Tap）的发生率，并记录在不同起搏周期下QT间期、动作电位时程（APD）及跨室壁复极离散度（TDa）的变化。结果在低钾、低镁台氏液灌流及2000～4000hi8慢频率刺激下，Sham、LVH、KN-92组（0．5μmol／L）及KN-93组（0．5μmol/L）EAD的发生率分别为0／10、10／10、9／10和5／10，Tdp的发生率分别为0／10、5／10、4／10和1／10；当KN-92组及KN-93组中药物浓度增至1μmol／L时，EAD的发生率分别为9／10和3／10，Tdp的发生率分别为4／10和1／10。而且KN-93组、KN-92组对QT间期、APD及TDR无明显影响（P〉0．05）。结论钙调蛋白激酶Ⅱ特异性抑制剂KN-93能够有效抑制心肌肥厚兔室性心律失常的发生，其主要作用机制是通过减少EAD的发生来实现。

英文摘要：

Objective To investigate the effect of KN-93, a calmedulin kinase Ⅱ inhibitor, on ventricular arrhythmias in rabbits with cardiac hypertrophy. Methods Female New Zealand white rabbits were randomly divided into four groups （n = 10 each） ： Sham; LVH; LVH ＋ KN-92 and LVH ＋ KN-93 group. LVH was induced by partially constricting the abdominal aorta. In Sham group, the abdominal aorta was exposed without constriction. Eight weeks later, the arterially perfused left ventricular wedge preparations were made and transmembrane action potentials （TAP） from epicardium and endocardium and transmural ECG were simultaneously recorded. Incidence of early afterdepolarization （EAD） and torsade de pointes （Tdp）, QT interval, action potential duration （APD） and transmural epolarization dispersion （TDR） at different cycle lengths were observed under slow stimulation （2000 -4000 ms）, hypokalemic （2 mmol/L） and hypomagnesaemic （0. 25 mmol/L） Tyrede＇s solution perfusion. Results Left ventricular hypertrophy was detected in LVH group by echocardiography and not affected by KN-92 and KN-93. Perfused with hypokalemic, hypomagnesaemic Tyrede＇s solution and under slow stimulation （2000 - 4000 ms）, the incidences of EAD and Tdp in Sham group, LVH group, LVH ＋ KN-92 group（0. 5 μmol/L ）and LVH ＋ KN-93 group （0. 5 μmol/L ） were 0/10, 10/10, 9/10, 5/10 and 0/10, 5/10, 4/10, 1/10, respectively. With 1 μmol/L KN-92 and KN-93, the incidences of EAD and Tdp in LVH ＋ KN-92 and LVH ＋ KN-93 group were 9/10, 3/10 and 4/10, 1/10 respectively. The QT interval, APD and TDR were not affected by KN-93. Condusion The calmedulin kinase Ⅱ inhibitor KN-93 can effectively suppress ventricular arrhythmias in rabbits with cardiac hypertrophy by decreasing EAD.