Gillis A M, Mathison H J, Kulisz E, Lester W M
Department of Medicine, The University of Calgary, Alberta, Canada.
J Cardiovasc Electrophysiol. 1998 Sep;9(9):988-97. doi: 10.1111/j.1540-8167.1998.tb00140.x.
Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts.
Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49+/-4 days postsurgery in the working heart mode using a blood-buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50+/-7 mmHg) afterload and high afterload (97+/-12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42+/-8 msec) compared with control hearts (26+/-8 msec, P < 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P < 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31+/-9 msec) compared with control hearts (30+/-9 msec, P = NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60+/-39 msec) compared with control hearts (30+/-13 msec, P < 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was -18+/-21 msec in control hearts and 7+/-21 ms in hypertrophied hearts (P < 0.05).
Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload-induced shortening of the APD. This effect may be due in part to altered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.
在心肌肥厚时可观察到心室复极离散度增加，且与心源性猝死相关。目前，关于心脏血流动力学和抗心律失常药物对疾病状态下复极离散度影响的信息较少。我们比较了增加后负荷和Ⅲ类抗心律失常药物多非利特对肥厚兔心与正常兔心心室复极离散度的影响。
通过腹主动脉缩窄诱导兔心肌肥厚。术后49±4天，在工作心脏模式下使用血液缓冲灌注液对离体心脏进行研究。在基线状态以及多非利特灌注期间，于低（50±7 mmHg）后负荷和高后负荷（97±12 mmHg）条件下，从心脏心外膜的八个部位测量动作电位时程（APD）。APD离散度定义为最大和最小APD之间的差值，在基线和低后负荷时，肥厚心脏的APD离散度（42±8毫秒）大于对照心脏（26±8毫秒，P<0.05）。增加后负荷使肥厚心脏的APD离散度降低（P<0.05），但对照心脏无此变化，且肥厚心脏的APD离散度（31±9毫秒）与对照心脏（30±9毫秒，P=无显著差异）相似。在多非利特灌注期间，低后负荷时肥厚心脏的APD离散度（60±39毫秒）仍大于对照心脏（30±13毫秒，P<0.05），但高后负荷时无此差异。增加后负荷使对照心脏大部分区域的APD缩短，而肥厚心脏在基线时APD无明显缩短，且在多非利特灌注期间有延长趋势。在多非利特灌注期间，后负荷增加后左心室后壁记录到的APD最大变化在对照心脏为-18±21毫秒，在肥厚心脏为7±21毫秒（P<0.05）。
后负荷增加后，肥厚心脏的心外膜APD离散度降低，且这种反应部分是由于后负荷诱导的APD缩短缺失所致。这种效应可能部分归因于在心肌肥厚情况下延迟整流电流对心脏负荷条件的反应改变。
