Modeling the physiological role of the heart and kidney in heart failure with preserved ejection fraction during baroreflex activation therapy.
Modeling the physiological role of the heart and kidney in heart failure with preserved ejection fraction during baroreflex activation therapy.
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模拟压力反射激活治疗期间射血分数保留的心力衰竭中心脏和肾脏的生理作用。
DOI：
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发表时间：
2022
期刊：
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通讯作者：
W. Pruett
中科院分区：
文献类型：
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作者：
J. Clemmer;W. Pruett
心力衰竭（HF）是导致死亡的主要原因，并且患病率正在增加。不幸的是，在射血分数降低（HFrEF）的HF患者中有效的治疗并未令人信服地显示射血分数保留（HFpEF）的HF患者的心血管死亡率降低。认为心脏中的高交感神经活动（SNA）在HF进展中起作用。临床试验表明，压力反射激活治疗可降低高血压HFpEF患者的左心室（LV）质量和血压（BP）;然而，其机制尚不清楚。在本研究中，我们使用HumMod，一个大型生理模型来模拟HFpEF和预测压力反射激活过程中全身和心脏血流动力学，SNA和心脏应力的时间依赖性变化。基线HFpEF模型与收缩压升高、舒张功能障碍、LV肥大和僵硬相关，与临床HFpEF相似。模拟12个月的压力反射激活导致收缩压（-25 mmHg）和LV质量（-15%）降低，与临床证据相似。压力反射激活还导致心脏和肾脏SNA持续降低（-22%），LV β1肾上腺素能功能改善。然而，当肾SNA被钳夹在基线水平时，压力反射诱导的血压降低和心脏应力、质量和功能的改善大多减弱。这些模拟表明，肾SNA的抑制可能是HFpEF中压力反射激活的心脏保护作用的主要决定因素。
Heart failure (HF) is a leading cause of death and is increasing in prevalence. Unfortunately, therapies that have been efficacious in HF patients with reduced ejection fraction (HFrEF) have not convincingly shown a reduction in cardiovascular mortality in patients with HF with preserved ejection fraction (HFpEF). It is thought that high sympathetic nerve activity (SNA) in the heart plays a role in HF progression. Clinical trials demonstrate that baroreflex activation therapy reduces left ventricular (LV) mass and blood pressure (BP) in hypertensive HFpEF patients; however, the mechanisms are unclear. In the present study, we used HumMod, a large physiology model to simulate HFpEF and predict the time-dependent changes in systemic and cardiac hemodynamics, SNA, and cardiac stresses during baroreflex activation. The baseline HFpEF model was associated with elevations in systolic BP, diastolic dysfunction, and LV hypertrophy and stiffness similar to clinical HFpEF. Simulating 12 months of baroreflex activation resulted in reduced systolic BP (-25 mmHg) and LV mass (-15%) similar to clinical evidence. Baroreflex activation also resulted in sustained decreases in cardiac and renal SNA (-22%) and improvement in LV β1 adrenergic function. However, the baroreflex induced reductions in BP and improvements in cardiac stresses, mass, and function were mostly attenuated when renal SNA was clamped at baseline levels. These simulations suggest that the suppression of renal SNA could be a primary determinant of the cardioprotective effects from baroreflex activation in HFpEF.