Lumped-parameter models of the pulmonary vasculature during the progression of pulmonary arterial hypertension.
Lumped-parameter models of the pulmonary vasculature during the progression of pulmonary arterial hypertension.
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DOI：
10.14814/phy2.13586
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发表时间：
2018-03
影响因子：
2.5
通讯作者：
Valdez-Jasso D
中科院分区：
文献类型：
--
作者：
Gerringer JW;Wagner JC;Vélez-Rendón D;Valdez-Jasso D
在Sprague-道利大鼠中进行了野百合碱诱导的肺动脉高压（PAH）的纵向研究，以研究血压升高产生的阻抗（包括阻力和顺应性）的变化。使用有创测量的血流作为输入，使用3-和4-元素Windkessel（3 WK，4 WK）型集总参数模型预测血压。通过最小二乘误差获得5个不同治疗组的电阻、顺应性和电感模型参数。治疗的动物达到高血压水平，其中血压从对照到PAH慢性阶段增加两倍（平均压力从24 ± 5到44 ± 6 mmHg，P < 0.0001），但血流总体上保持不受影响。与血压一样，PAH晚期波反射系数显著增加（0.26 ± 0.09至0.52 ± 0.09，P < 0.0002）。我们的建模工作表明，在疾病进展过程中，阻力和顺应性发生了变化，其中顺应性的变化发生在阻力变化之前。然而，阻力和顺应性不是直接负相关的。随着PAH的发展，阻力呈非线性增加（Rd呈指数增加，R以较慢的速度增加），而顺应性呈线性下降。虽然3 WK和4 WK模型捕获了PAH期间肺血管中的压力-流量关系，但Akaike信息标准和灵敏度分析的结果使我们得出结论，3 WK是该系统最稳健和准确的模型。对于研究人群，包括预测模型参数的95%置信区间。这项工作确立了对PAH中发生的复杂重塑过程的见解。
A longitudinal study of monocrotaline‐induced pulmonary arterial hypertension (PAH) was carried out in Sprague‐Dawley rats to investigate the changes in impedance (comprising resistance and compliance) produced by elevated blood pressure. Using invasively measured blood flow as an input, blood pressure was predicted using 3‐ and 4‐element Windkessel (3WK, 4WK) type lumped‐parameter models. Resistance, compliance, and inductance model parameters were obtained for the five different treatment groups via least‐squares errors. The treated animals reached levels of hypertension, where blood pressure increased two folds from control to chronic stage of PAH (mean pressure went from 24 ± 5 to 44 ± 6 mmHg, P < 0.0001) but blood flow remained overall unaffected. Like blood pressure, the wave‐reflection coefficient significantly increased at the advanced stage of PAH (0.26 ± 0.09 to 0.52 ± 0.09, P < 0.0002). Our modeling efforts revealed that resistances and compliance changed during the disease progression, where changes in compliance occur before the changes in resistance. However, resistance and compliance are not directly inversely related. As PAH develops, resistances increase nonlinearly (R d exponentially and R at a slower rate) while compliance linearly decreases. And while 3WK and 4WK models capture the pressure‐flow relation in the pulmonary vasculature during PAH, results from Akaike Information Criterion and sensitivity analysis allow us to conclude that the 3WK is the most robust and accurate model for this system. Ninety‐five percent confidence intervals of the predicted model parameters are included for the population studied. This work establishes insight into the complex remodeling process occurring in PAH.