Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo.
Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo.
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发表时间：
2004
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通讯作者：
S. Hao;D. Christini;K. Stein;Peter N. Jordan;S. Iwai;O. Bramwell;S. Markowitz;S. Mittal;B. Lerman
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作者：
S. Hao;D. Christini;K. Stein;Peter N. Jordan;S. Iwai;O. Bramwell;S. Markowitz;S. Mittal;B. Lerman
动作电位时程（APD）恢复曲线的斜率可能是发生室颤倾向的重要决定因素，斜率越陡，则与致心律失常性底物相关。我们假设β受体阻滞剂减少心脏性猝死的一种机制是使APD恢复曲线变平。因此，我们研究了艾司洛尔输注是否在体内调节APD恢复曲线。在10头约克郡猪中，在基础状态下右心室心尖起搏期间和艾司洛尔输注期间，通过使用贴靠右心室间隔放置的单相动作电位导管测量90%复极时的APD，确定动态APD恢复曲线。APD恢复曲线符合三参数（a，B，c）指数方程APD = a。[1 - e（（-B.DI））] + c，其中DI是舒张间期。艾司洛尔降低了最大APD斜率，0.68 +/- 0.14 vs. 0.94 +/- 0.24（基线），P = 0.002，并在较短DI（75和100 ms）时使APD恢复曲线变平（P < 0.05）。为了比较类似稳态下APD恢复曲线的斜率，还使用关系CL = APD + DI计算了恢复曲线与代表200、225、250、275和300 ms固定周期长度（CL）下起搏的线之间交叉点的斜率。艾司洛尔在CLs 200-275 ms时降低APD恢复斜率（P < 0.05）。艾司洛尔在体内延长心脏APD恢复曲线，特别是在较短的CL和DI时。这可能代表了β受体阻滞剂预防心源性猝死的一种新机制。
The slope of the action potential duration (APD) restitution curve may be a significant determinant of the propensity to develop ventricular fibrillation, with steeper slopes associated with a more arrhythmogenic substrate. We hypothesized that one mechanism by which beta-blockers reduce sudden cardiac death is by flattening the APD restitution curve. Therefore, we investigated whether infusion of esmolol modulates the APD restitution curve in vivo. In 10 Yorkshire pigs, dynamic APD restitution curves were determined from measurements of APD at 90% repolarization with a monophasic action potential catheter positioned against the right ventricular septum during right ventricular apical pacing in the basal state and during infusion of esmolol. APD restitution curves were fitted to the three-parameter (a, b, c) exponential equation, APD = a.[1 - e((-b.DI))] + c, where DI is the diastolic interval. Esmolol decreased the maximal APD slope, 0.68 +/- 0.14 vs. 0.94 +/- 0.24 (baseline), P = 0.002, and flattened the APD restitution curve at shorter DIs, 75 and 100 ms (P < 0.05). To compare the slopes of the APD restitution curves at similar steady states, slopes were also computed at points of intersection between the restitution curve and the lines representing pacing at a fixed cycle length (CL) of 200, 225, 250, 275, and 300 ms using the relationship CL = APD + DI. Esmolol decreased APD restitution slopes at CLs 200-275 ms (P < 0.05). Esmolol flattens the cardiac APD restitution curve in vivo, particularly at shorter CLs and DIs. This may represent a novel mechanism by which beta-blockers prevent sudden cardiac death.