Bragard Jean, Sankarankutty Aparna C, Sachse Frank B
Department of Physics and Applied Mathematics, University of Navarra, Pamplona, Spain.
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, United States.
Front Physiol. 2019 Apr 3;10:337. doi: 10.3389/fphys.2019.00337. eCollection 2019.
Defibrillation is a well-established therapy for atrial and ventricular arrhythmia. Here, we shed light on defibrillation in the fibrotic heart. Using the extended bidomain model of electrical conduction in cardiac tissue, we assessed the influence of fibrosis on the strength of virtual electrodes caused by extracellular electrical current. We created one-dimensional models of rabbit ventricular tissue with a central patch of fibrosis. The fibrosis was incorporated by altering volume fractions for extracellular, myocyte and fibroblast domains. In our prior work, we calculated these volume fractions from microscopic images at the infarct border zone of rabbit hearts. An average and a large degree of fibrosis were modeled. We simulated defibrillation by application of an extracellular current for a short duration (5 ms). We explored the effects of myocyte-fibroblast coupling, intra-fibroblast conductivity and patch length on the strength of the virtual electrodes present at the borders of the normal and fibrotic tissue. We discriminated between effects on myocyte and fibroblast membranes at both borders of the patch. Similarly, we studied defibrillation in two-dimensional models of fibrotic tissue. Square and disk-like patches of fibrotic tissue were embedded in control tissue. We quantified the influence of the geometry and fibrosis composition on virtual electrode strength. We compared the results obtained with a square and disk shape of the fibrotic patch with results from the one-dimensional simulations. Both, one- and two-dimensional simulations indicate that extracellular current application causes virtual electrodes at boundaries of fibrotic patches. A higher degree of fibrosis and larger patch size were associated with an increased strength of the virtual electrodes. Also, patch geometry affected the strength of the virtual electrodes. Our simulations suggest that increased fibroblast-myocyte coupling and intra-fibroblast conductivity reduce virtual electrode strength. However, experimental data to constrain these modeling parameters are limited and thus pinpointing the magnitude of the reduction will require further understanding of electrical coupling of fibroblasts in native cardiac tissues. We propose that the findings from our computational studies are important for development of patient-specific protocols for internal defibrillators.
除颤是一种治疗心房和心室心律失常的成熟疗法。在此，我们揭示纤维化心脏中的除颤情况。利用心脏组织中电传导的扩展双域模型，我们评估了纤维化对细胞外电流引起的虚拟电极强度的影响。我们创建了具有中央纤维化斑块的兔心室组织一维模型。通过改变细胞外、心肌细胞和成纤维细胞区域的体积分数来纳入纤维化。在我们之前的工作中，我们从兔心脏梗死边缘区的微观图像计算出这些体积分数。模拟了平均程度和高度的纤维化。我们通过施加短持续时间（5毫秒）的细胞外电流来模拟除颤。我们探讨了心肌细胞 - 成纤维细胞耦合、成纤维细胞内电导率和斑块长度对正常组织和纤维化组织边界处虚拟电极强度的影响。我们区分了对斑块两侧心肌细胞膜和成纤维细胞膜的影响。同样，我们研究了纤维化组织二维模型中的除颤。纤维化组织的方形和盘状斑块嵌入对照组织中。我们量化了几何形状和纤维化组成对虚拟电极强度的影响。我们将纤维化斑块为方形和盘状时获得的结果与一维模拟结果进行了比较。一维和二维模拟均表明，施加细胞外电流会在纤维化斑块边界处产生虚拟电极。更高程度的纤维化和更大的斑块尺寸与虚拟电极强度增加相关。此外，斑块几何形状影响虚拟电极强度。我们的模拟表明，增加的成纤维细胞 - 心肌细胞耦合和成纤维细胞内电导率会降低虚拟电极强度。然而，限制这些建模参数的实验数据有限，因此要确定降低的幅度需要进一步了解天然心脏组织中成纤维细胞的电耦合。我们认为，我们的计算研究结果对于制定针对植入式除颤器的患者特异性方案很重要。
