Fouts Kristen, Fernandes Brian, Mal Niladri, Liu Jinqiu, Laurita Kenneth R
Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University, Cleveland, Ohio 44109, USA.
Heart Rhythm. 2006 Apr;3(4):452-61. doi: 10.1016/j.hrthm.2005.12.016.
The purpose of this study is to test our hypothesis that injection of skeletal myoblasts (SkMbs) into viable tissue may alter impulse conduction but that injections into nonviable tissue (scar) will have negligible impact.
Myocardial infarction (MI) is a major public health problem. SkMb transplantation after MI has been shown to have some beneficial effect on hemodynamic function. Previous studies have indicated that SkMbs do not electrically couple with viable host myocardium in vivo.
We used optical mapping to measure impulse propagation and arrhythmia inducibility in the canine left ventricular wedge preparation with and without MI. MI was created by temporary ligation of a branch of the left anterior descending coronary artery (LAD) (7.0 +/- 3.8 ng/mL troponin 24 hours after MI). Labeled SkMbs (10(8) in 4 mL of serum-free basal solution) were injected from the epicardium (20-40 0.1 mL injections) into normal myocardium (n = 8) or the central zone of the MI (n = 6).
During endocardial pacing in the absence of MI, transmural conduction velocity was similar with (35.75 +/- 3.4 cm/s) and without (37.42 +/- 3.6 cm/s) SkMb transplantation. However, pacing from the epicardium resulted in conduction slowing in regions that were DiI-positive and associated with the expression of skeletal myosin (fast) but not connexin-43. In all preparations with MI (n = 13), abnormal impulse propagation was seen regardless of SkMb transplantation. Arrhythmias (at least one extra beat after standard programmed stimulation) occurred most frequently in preparations with MI independent of SkMb transplantation. In preparations without MI (n = 8), SkMb transplantation did not significantly increase arrhythmia inducibility.
We conclude that SkMbs transplanted into normal myocardium can cause abnormal impulse propagation. These data suggest that the location of SkMb transplantation may influence arrhythmia vulnerability associated with MI.
本研究旨在验证我们的假设，即向存活组织注射骨骼肌成肌细胞（SkMbs）可能会改变冲动传导，但向非存活组织（瘢痕）注射的影响可忽略不计。
心肌梗死（MI）是一个主要的公共卫生问题。MI后进行SkMb移植已显示出对血流动力学功能有一些有益作用。先前的研究表明，SkMbs在体内不会与存活的宿主心肌形成电偶联。
我们使用光学标测法测量在有或没有MI的犬左心室楔形标本中的冲动传播和心律失常诱导性。通过临时结扎左前降支冠状动脉（LAD）的一个分支来制造MI（MI后24小时肌钙蛋白为7.0±3.8 ng/mL）。将标记的SkMbs（4 mL无血清基础溶液中含10⁸个）从心外膜注射（20 - 40次0.1 mL注射）到正常心肌（n = 8）或MI的中心区域（n = 6）。
在没有MI的情况下进行心内膜起搏时，有（35.75±3.4 cm/s）和没有（37.42±3.6 cm/s）SkMb移植时跨壁传导速度相似。然而，从心外膜起搏会导致DiI阳性且与骨骼肌肌球蛋白（快）表达相关但与连接蛋白43无关的区域传导减慢。在所有有MI的标本（n = 13）中，无论是否进行SkMb移植，均可见异常冲动传播。心律失常（标准程序刺激后至少有一次额外搏动）在有MI的标本中最常发生，与SkMb移植无关。在没有MI的标本（n = 8）中，SkMb移植并未显著增加心律失常诱导性。
我们得出结论，移植到正常心肌中的SkMbs可导致异常冲动传播。这些数据表明，SkMb移植的位置可能会影响与MI相关的心律失常易感性。
