Punske Bonnie B, Taccardi Bruno, Steadman Bruce, Ershler Philip R, England Alice, Valencik Maria L, McDonald John A, Litwin Sheldon E
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City Utah, 84112-5000, USA.
J Electrocardiol. 2005 Oct;38(4 Suppl):40-4. doi: 10.1016/j.jelectrocard.2005.06.097.
Epicardial potentials reveal the strong effects of fiber anisotropy, rotation, imbrication, and coupling on propagation in the intact heart. From the patterns of the surface potentials, we can obtain information about the local fiber orientation, anisotropy, the transmural fiber rotation, and which direction the wave front is traveling through the wall. In this study, lessons learned from epicardial potential mapping of large hearts were applied to studies conducted in genetically altered mouse hearts.
An inducible model of the overexpression of a gain-of-function alpha5 integrin (cytoplasmic domain truncation) was created in mouse. After 3 days of administration of doxycycline, the animals exhibited an altered electrical phenotype of markedly reduced amplitude of the QRS complex on the surface electrocardiogram. Epicardial potentials were recorded from Langendorff-perfused mouse hearts with alpha5 integrin gain-of-function mutations and from wild-type (WT) control hearts. A cylindrical electrode array consisting of 184 sites with 1-mm uniform interelectrode spacing was placed around the heart, and unipolar electrograms were recorded during atrial and ventricular stimulation at different basic cycle lengths.
The total ventricular activation time for the transgenic animals was greater than that of the WT hearts for atrial and ventricular pacing locations. The isopotential maps from the mutated hearts showed a loss of anisotropy, as revealed by the more rounded and less elliptically shaped wave fronts seen immediately after epicardial point stimulation when compared with WT hearts. The weaker potential maxima in the mutated hearts did not exhibit the normal expansion and rotation associated with an advancing wave front in a normal heart, suggesting abnormalities in myocyte coupling in these hearts. Isopotential maps provided additional information about fiber architecture from the electric field that was not obtained from optical recordings alone. These findings provided a phenotypic characterization and specific insights into the mechanisms of the electrical abnormalities associated with altered integrin signaling in cardiac myocytes.
心外膜电位揭示了纤维各向异性、旋转、叠瓦状排列和耦合对完整心脏中电传导的强大影响。从表面电位模式中，我们可以获得有关局部纤维方向、各向异性、跨壁纤维旋转以及波阵面穿过心肌壁传播方向的信息。在本研究中，将从大型心脏的心外膜电位标测中获得的经验应用于对基因改造小鼠心脏的研究。
在小鼠中建立了一种可诱导的功能获得性α5整合素（胞质结构域截短）过表达模型。在给予强力霉素3天后，动物表现出心电图表面QRS波群幅度明显降低的电表型改变。从具有α5整合素功能获得性突变的Langendorff灌注小鼠心脏和野生型（WT）对照心脏记录心外膜电位。一个由184个位点组成的圆柱形电极阵列，电极间距均匀为1毫米，放置在心脏周围，并在不同基础周期长度的心房和心室刺激期间记录单极电图。
转基因动物的总心室激活时间在心房和心室起搏部位均长于WT心脏。与WT心脏相比，突变心脏的心外膜点刺激后立即出现的等电位图显示各向异性丧失，表现为波阵面更圆且椭圆形更不明显。突变心脏中较弱的电位最大值未表现出正常心脏中与前进波阵面相关的正常扩展和旋转，提示这些心脏中肌细胞耦合存在异常。等电位图从电场提供了有关纤维结构的额外信息，这是单独从光学记录中无法获得的。这些发现为与心肌细胞中整合素信号改变相关的电异常机制提供了表型特征和具体见解。
