We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting. Porcine (n = 9) and human (n = 4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. A total of 1 mM of carbenoxolone was administered at 5 ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed. We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)_max increased between baseline and carbenoxolone (47.9 ± 4.1–67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and carbenoxolone were fractionation + 185.3%, endpoint amplitude − 106.9%, S-endpoint gradient + 54.9%, S point − 39.4%, RS ratio + 38.6% and (-dV/dt)_max − 20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates.

我们描述了用于实时电生理学研究的人类和大型动物Langendorff实验仪器，并测量了由于人和猪心脏中的间隙连接解偶联而引起的电生理变化。所得的离体完整人类和猪模型可以弥合较小的简单实验室模型与临床研究之间的翻译鸿沟。特别是，由于电生理模型对远场信号，电极接触问题和运动伪影的影响，因此会受益于大心脏的更大的心肌质量，因此可以更紧密地模仿临床环境。猪（n  = 9）和人（n = 4）在定制设计的Langendorff装置上灌注供体心脏。在左心房和左心室的16个部位收集心外膜电描记图。总共以5 ml / min的剂量施用1 mM的羧苄隆以诱导细胞解偶联，然后在相同的位置重复记录。分析了电图特征的变化。我们证明了完整的猪和人心脏电生理与药理学调制的受控离体模型的可行性。羧苄酮可减少细胞偶联并改变接触电描记图功能。从刺激伪像到（-dV / dt）_{最大值的时间}在基线和羧甲基环戊烯酮之间增加（47.9±4.1–67.2±2.7 ms），表明传导减慢。基线和羧苄索隆之间百分比变化最大的特征是分馏+ 185.3％，终点振幅-106.9％，S终点梯度+ 54.9％，S点-39.4％，RS比+ 38.6％和（-dV / dt）_max − 20.9％。该方法学工具的生理相关性在于，它提供了一个模型，可以进一步研究药理学诱导的心律失常前体。