Walton Richard D, Martinez Marine E, Bishop Martin J, Hocini Mélèze, Haïssaguerre Michel, Plank Gernot, Bernus Olivier, Vigmond Edward J
Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France
Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France.
Cardiovasc Res. 2014 Sep 1;103(4):629-40. doi: 10.1093/cvr/cvu165. Epub 2014 Jul 3.
To elucidate the properties of the PMJ and myocardium underlying these effects. Transmural heterogeneity of action potential duration (APD) is known to play an important role in arrhythmogenesis. Regions of non-uniformities of APD gradients often overlap considerably with the location of Purkinje-muscle junctions (PMJs). We therefore hypothesized that such junctions are novel sources of local endocardial and transmural heterogeneity of repolarization, and that remodelling due to heart failure modulates this response.
Spatial gradients of endocardial APD in left ventricular wedge preparations from healthy sheep (n = 5) were correlated with locations of PMJs identified through Purkinje stimulation under optical mapping. APD prolongation was dependent on proximity of the PMJ to the imaged surface, whereby shallow PMJs significantly modulated local APD when stimulating either Purkinje (P = 0.0116) or endocardium (P = 0.0123). In addition, we model a PMJ in 5 × 5× 10 mm transmural tissue wedges using healthy and novel failing human ventricular and Purkinje ionic models. Short distances of the PMJ to cut surfaces (<0.875 mm) revealed that APD maxima were localized to the PMJ in healthy myocardium, whereas APD minima were observed in failing myocardium. Amplitudes and spatial gradients of APD were prominent at functional PMJs and quiescent PMJs. Furthermore, increasing the extent of Purkinje fibre branching or decreasing tissue conductivity augmented local APD prolongation in both failing and non-failing models.
The Purkinje network has the potential to influence myocardial AP morphology and rate-dependent behaviour, and furthermore to underlie enhanced transmural APD heterogeneities and spatial gradients of APD in non-failing and failing myocardium.
阐明这些效应背后的浦肯野肌连接（PMJ）和心肌的特性。动作电位时程（APD）的跨壁异质性在心律失常的发生中起着重要作用。APD梯度不均匀的区域通常与浦肯野 - 肌肉连接（PMJ）的位置有相当大的重叠。因此，我们假设这种连接是复极化局部心内膜和跨壁异质性的新来源，并且心力衰竭引起的重塑会调节这种反应。
在光学标测下，通过浦肯野刺激确定健康绵羊（n = 5）左心室楔形标本中心内膜APD的空间梯度与PMJ的位置相关。APD延长取决于PMJ与成像表面的接近程度，当刺激浦肯野纤维（P = 0.0116）或心内膜（P = 0.0123）时，浅PMJ会显著调节局部APD。此外，我们使用健康和新型衰竭的人心室及浦肯野离子模型，在5×5×10mm的跨壁组织楔形物中模拟PMJ。PMJ到切割表面的短距离（<0.875mm）表明，在健康心肌中APD最大值位于PMJ处，而在衰竭心肌中观察到APD最小值。在功能性PMJ和静止PMJ处，APD的幅度和空间梯度都很显著。此外，在衰竭和非衰竭模型中，增加浦肯野纤维分支程度或降低组织电导率都会增强局部APD延长。
浦肯野网络有可能影响心肌动作电位形态和频率依赖性行为，并且进一步成为非衰竭和衰竭心肌中跨壁APD异质性增强和APD空间梯度的基础。
