Clayton Richard H, Sridhar S
Insigneo Institute for in-silico Medicine and Department of Computer Science, University of Sheffield, Sheffield, United Kingdom.
Front Physiol. 2024 Jun 28;15:1403545. doi: 10.3389/fphys.2024.1403545. eCollection 2024.
Fibrotic scar in the heart is known to act as a substrate for arrhythmias. Regions of fibrotic scar are associated with slowed or blocked conduction of the action potential, but the detailed mechanisms of arrhythmia formation are not well characterised and this can limit the effective diagnosis and treatment of scar in patients. The aim of this computational study was to evaluate different representations of fibrotic scar in models of 2D 10 10 cm ventricular tissue, where the region of scar was defined by sampling a Gaussian random field with an adjustable length scale of between 1.25 and 10.0 mm. Cellular electrophysiology was represented by the Ten Tusscher 2006 model for human ventricular cells. Fibrotic scar was represented as a spatially varying diffusion, with different models of the boundary between normal and fibrotic tissue. Dispersion of activation time and action potential duration (APD) dispersion was assessed in each sample by pacing at an S1 cycle length of 400 ms followed by a premature S2 beat with a coupling interval of 323 ms. Vulnerability to reentry was assessed with an aggressive pacing protocol. In all models, simulated fibrosis acted to delay activation, to increase the dispersion of APD, and to generate re-entry. A higher incidence of re-entry was observed in models with simulated fibrotic scar at shorter length scale, but the type of model used to represent fibrotic scar had a much bigger influence on the incidence of reentry. This study shows that in computational models of fibrotic scar the effects that lead to either block or propagation of the action potential are strongly influenced by the way that fibrotic scar is represented in the model, and so the results of computational studies involving fibrotic scar should be interpreted carefully.
众所周知，心脏中的纤维化瘢痕是心律失常的基础。纤维化瘢痕区域与动作电位传导减慢或阻滞有关，但心律失常形成的详细机制尚未得到充分表征，这可能会限制对患者瘢痕的有效诊断和治疗。本计算研究的目的是评估二维10×10平方厘米心室组织模型中纤维化瘢痕的不同表示形式，其中瘢痕区域通过对长度尺度在1.25至10.0毫米之间可调的高斯随机场进行采样来定义。细胞电生理学由Ten Tusscher 2006年的人类心室细胞模型表示。纤维化瘢痕表示为空间变化的扩散，正常组织和纤维化组织之间的边界采用不同模型。通过以400毫秒的S1周期长度起搏，随后以323毫秒的耦合间期进行早搏S2搏动，评估每个样本中的激活时间离散度和动作电位持续时间（APD）离散度。采用激进的起搏方案评估折返易感性。在所有模型中，模拟纤维化均导致激活延迟、APD离散度增加并产生折返。在长度尺度较短的模拟纤维化瘢痕模型中观察到更高的折返发生率，但用于表示纤维化瘢痕的模型类型对折返发生率的影响要大得多。本研究表明，在纤维化瘢痕的计算模型中，导致动作电位阻滞或传播的效应受到模型中纤维化瘢痕表示方式的强烈影响，因此涉及纤维化瘢痕的计算研究结果应谨慎解释。
