Watrous Raymond L, Chin Alvin J
1 Division of Cardiology, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
World J Pediatr Congenit Heart Surg. 2017 Mar;8(2):148-160. doi: 10.1177/2150135116679831.
For patients with the Fontan circulatory arrangement, angiotensin-converting enzyme inhibition, guanylate cyclase activation, phosphodiesterase 5 inhibition, and endothelin receptor antagonism have so far resulted in little or no improvement in [Formula: see text] or peak cardiac index (CI), suggesting that our understanding of the factors that most impact the exercise hemodynamics is incomplete.
To facilitate comparisons with clinical reports of the exercise performance of preadolescent Fontan patients, we rescaled our previously reported computational models of a two-year-old normal child and similarly aged Fontan patient, extended our Fontan model to capture the nonlinear relationship between flow and resistance quantified from previous computational fluid dynamic analyses of the total cavopulmonary connection (TCPC), and added respiration as well as skeletal muscle contraction.
(1) Without respiration, the computational model for both the normal and the Fontan cannot attain the values for CI at peak exercise reported in the clinical literature, (2) because flow through the TCPC is much greater during inspiration than during expiration, the effect on the CI of the dynamic (flow-related) TCPC resistance is much more dramatic during exercise than it is in breath-hold mode at rest, and (3) coupling breathing with skeletal muscle contraction leads to the highest augmentation of cardiac output, that is, the skeletal muscle pump is most effective when the intrathoracic pressure is at a minimum-at peak inspiration.
Novel insights emerge when a Fontan model incorporating dynamic TCPC resistance, full respiration, and skeletal muscle contraction can be compared to the model of the normal.
对于采用Fontan循环系统的患者，迄今为止，血管紧张素转换酶抑制、鸟苷酸环化酶激活、磷酸二酯酶5抑制以及内皮素受体拮抗等措施，在[公式：见正文]或峰值心脏指数（CI）方面几乎没有改善，这表明我们对最影响运动血流动力学的因素的理解并不完整。
为便于与青春期前Fontan患者运动表现的临床报告进行比较，我们重新调整了之前报道的两岁正常儿童和同龄Fontan患者的计算模型，扩展了我们的Fontan模型，以捕捉从先前对全腔肺连接（TCPC）的计算流体动力学分析中量化的流量与阻力之间的非线性关系，并增加了呼吸以及骨骼肌收缩。
（1）在没有呼吸的情况下，正常和Fontan的计算模型都无法达到临床文献中报道的运动峰值时的CI值；（2）由于在吸气过程中通过TCPC的流量比呼气过程中要大得多，所以运动期间动态（与流量相关）TCPC阻力对CI的影响比静息屏气模式下更为显著；（3）将呼吸与骨骼肌收缩相结合会导致心输出量增加最多，也就是说，当胸内压处于最低值——吸气峰值时，骨骼肌泵最为有效。
当将包含动态TCPC阻力、完全呼吸和骨骼肌收缩的Fontan模型与正常模型进行比较时，会出现新的见解。
