Haberbusch Max, De Luca Daniela, Moscato Francesco
Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria.
Front Physiol. 2020 Nov 6;11:579449. doi: 10.3389/fphys.2020.579449. eCollection 2020.
During heart transplantation (HTx), cardiac denervation is inevitable, thus typically resulting in chronic resting tachycardia and chronotropic incompetence with possible consequences in patient quality of life and clinical outcomes. To this date, knowledge of hemodynamic changes early after HTx is still incomplete. This study aims at providing a model-based description of the complex hemodynamic changes at rest and during exercise in HTx recipients (HTxRs). A numerical model of early HTxRs is developed that integrates intrinsic and autonomic heart rate (HR) control into a lumped-parameter cardiovascular system model. Intrinsic HR control is realized by a single-cell sinoatrial (SA) node model. Autonomic HR control is governed by aortic baroreflex and pulmonary stretch reflex and modulates SA node activity through neurotransmitter release. The model is tuned based on published clinical data of 15 studies. Simulations of rest and exercise are performed to study hemodynamic changes associated with HTxRs. Simulations of HTxRs at rest predict a substantially increased HR [93.8 vs. 69.5 beats/min (bpm)] due to vagal denervation while maintaining normal cardiac output (CO) (5.2 vs. 5.6 L/min) through a reduction in stroke volume (SV) (55.4 vs. 82 mL). Simulations of exercise predict markedly reduced peak CO (13 vs. 19.8 L/min) primarily resulting from diminished peak HRs (133.9 vs. 169 bpm) and reduced ventricular contractility. Yet, the model results show that HTxRs can maintain normal CO for low- to medium-intensity exercise by increased SV augmentation through the Frank-Starling mechanism. Relevant hemodynamic changes occur after HTx. Simulations suggest that (1) increased resting HRs solely result from the absence of vagal tone; (2) chronotropic incompetence is the main limiting factor of exercise capacity whereby peripheral factors play a secondary role; and (3) despite the diminished exercise capacity, HTxRs can compensate chronotropic incompetence by a preload-mediated increase in SV augmentation and thus maintain normal CO in low- to medium-intensity exercise.
在心脏移植（HTx）过程中，心脏去神经支配不可避免，通常会导致慢性静息性心动过速和变时性功能不全，这可能会对患者的生活质量和临床结局产生影响。迄今为止，关于HTx术后早期血流动力学变化的认识仍不完整。本研究旨在提供一个基于模型的描述，以阐述HTx受者（HTxRs）在静息和运动状态下复杂的血流动力学变化。构建了一个早期HTxRs的数值模型，该模型将内在和自主心率（HR）控制整合到一个集总参数心血管系统模型中。内在HR控制通过单细胞窦房（SA）结模型实现。自主HR控制由主动脉压力反射和肺牵张反射调节，并通过神经递质释放调节SA结活动。该模型基于15项研究已发表的临床数据进行了调整。进行静息和运动状态的模拟，以研究与HTxRs相关的血流动力学变化。静息状态下HTxRs的模拟预测，由于迷走神经去支配，心率显著增加[93.8 vs. 69.5次/分钟（bpm）]，同时通过减少每搏输出量（SV）（55.4 vs. 82 mL）维持正常的心输出量（CO）（5.2 vs. 5.6 L/分钟）。运动状态的模拟预测，峰值CO显著降低（13 vs. 19.8 L/分钟），主要是由于峰值心率降低（133.9 vs. 169 bpm）和心室收缩力减弱。然而，模型结果表明，HTxRs可通过Frank-Starling机制增加SV增强，从而在低至中等强度运动中维持正常的CO。HTx术后会发生相关的血流动力学变化。模拟结果表明：（1）静息心率增加仅源于迷走神经张力缺失；（2）变时性功能不全是运动能力的主要限制因素，而外周因素起次要作用；（3）尽管运动能力下降，但HTxRs可通过前负荷介导的SV增强增加来补偿变时性功能不全，从而在低至中等强度运动中维持正常的CO。
