Sachetto Rafael, Alonso Sergio, Dos Santos Rodrigo Weber
Department of Computer Science, Universidade Federal de São João del-Rei, São João del-Rei, Brazil.
Graduate Program in Computational Modeling, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.
Front Physiol. 2018 Jun 22;9:764. doi: 10.3389/fphys.2018.00764. eCollection 2018.
During cardiac diseases many types of anatomical and functional remodeling of cardiac tissue can occur. In this work, we focus on two conditions: hypoxia and fibrosis, which are part of complex pathological modifications that take place in many cardiac diseases (hypertrophic cardiomyopathy, hypertensive heart disease, and recurrent myocardial infarction) and respiratory diseases (obstructive pulmonary disease, obstructive sleep apnea, and cystic fibrosis). Using computational models of cardiac electrophysiology, we evaluate if the interplay between hypoxia and fibrosis is sufficient to trigger cardiac arrhythmia. We study the mechanisms behind the generation of ectopic beats, an arrhythmic trigger also known as premature ventricular contractions (PVCs), in regions with high hypoxia and fibrosis. First, we modify an electrophysiological model of myocytes of the human left ventricle to include the effects of hypoxia. Second, diffuse fibrosis is modeled by randomly replacing cardiac myocytes by non-excitable and non-conducting cells. The Monte Carlo method is used to evaluate the probability of a region to generate ectopic beats with respect to different levels of hypoxia and fibrosis. In addition, we evaluate the minimum size of three-dimensional slabs needed to sustain reentries for different stimulation protocols. The observed mechanism behind the initiation of ectopic beats is unidirectional block, giving rise to sustained micro-reentries inside the region with diffuse fibrosis and hypoxia. In summary, our results suggest that hypoxia and fibrosis are sufficient for the creation of a focal region in the heart that generates PVCs.
在心脏疾病期间，心脏组织会发生多种类型的解剖学和功能性重塑。在这项研究中，我们关注两种情况：缺氧和纤维化，它们是许多心脏疾病（肥厚型心肌病、高血压性心脏病和复发性心肌梗死）以及呼吸系统疾病（阻塞性肺疾病、阻塞性睡眠呼吸暂停和囊性纤维化）中发生的复杂病理改变的一部分。使用心脏电生理学计算模型，我们评估缺氧和纤维化之间的相互作用是否足以引发心律失常。我们研究在高缺氧和纤维化区域中异位搏动（一种也称为室性早搏（PVCs）的心律失常触发因素）产生的机制。首先，我们修改人类左心室心肌细胞的电生理模型以纳入缺氧的影响。其次，通过用不可兴奋和不导电的细胞随机替代心肌细胞来模拟弥漫性纤维化。蒙特卡罗方法用于评估相对于不同程度的缺氧和纤维化，一个区域产生异位搏动的概率。此外，我们评估了不同刺激方案下维持折返所需的三维平板的最小尺寸。观察到的异位搏动起始背后的机制是单向阻滞，在弥漫性纤维化和缺氧区域内产生持续的微折返。总之，我们的结果表明，缺氧和纤维化足以在心脏中形成一个产生室性早搏的局灶区域。
