Multiscale model of the physiological control of myocardial perfusion to delineate putative metabolic feedback mechanisms.
Multiscale model of the physiological control of myocardial perfusion to delineate putative metabolic feedback mechanisms.
复制标题
心肌灌注的生理控制的多尺度模型，以描述推定的代谢反馈机制。
DOI：
10.1113/jp282237
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Beard DA
中科院分区：
文献类型：
--
作者：
Gharahi H;Figueroa CA;Tune JD;Beard DA
冠状动脉血流受到严格调节，以确保心肌氧输送通过肌源性、神经和代谢机制的同时作用满足局部代谢需求。虽然存在几种相互竞争的假设，但局部代谢机制的具体性质仍然定义不清。为了深入了解假定的代谢反馈机制的可行性和并行调节机制的协调作用，我们应用多尺度建模框架来分析猪体内心脏中冠状动脉压力、流量和心肌氧输送的实验数据。建模框架集成了先前建立的用于解释透壁血流动力学变化的心肌灌注的集总参数模型和用于模拟三个心肌层中的每一个中的血管张力的简单血管力学模型。阻力血管力学模型中的血管张力受来自肌源性、代谢和自主控制机制的输入刺激支配。七个竞争配方的代谢反馈机制中实施的建模框架，相关的模型模拟进行了比较，在一系列的实验条件下的冠状动脉压力和流量的实验数据，旨在询问管理控制机制。分析确定了七个测试模型中最可能的代谢机制，其中代谢信号因子的产生与MVO2成比例，并且递送与流量成比例。最后，所识别的模型进行验证的基础上比较的模拟数据的心肌灌注反应有意识的运动，没有用于模型识别。
Coronary blood flow is tightly regulated to ensure that myocardial oxygen delivery meets local metabolic demand via the concurrent action of myogenic, neural, and metabolic mechanisms. While several competing hypotheses exist, the specific nature of the local metabolic mechanism(s) remains poorly defined. To gain insights into the viability of putative metabolic feedback mechanisms and into the coordinated action of parallel regulatory mechanisms, we applied a multi-scale modeling framework to analyze experimental data on coronary pressure, flow, and myocardial oxygen delivery in the porcine heart in vivo. The modeling framework integrates a previously established lumped-parameter model of myocardial perfusion used to account for transmural hemodynamic variations and a simple vessel mechanics model used to simulate the vascular tone in each of three myocardial layers. Vascular tone in the resistance vessel mechanics model is governed by input stimuli from the myogenic, metabolic, and autonomic control mechanisms. Seven competing formulations of the metabolic feedback mechanism are implemented in the modeling framework, and associated model simulations are compared to experimental data on coronary pressures and flows under a range of experimental conditions designed to interrogate the governing control mechanisms. Analysis identifies a maximally likely metabolic mechanism among the seven tested models, in which production of a metabolic signaling factor is proportional to MVO2 and delivery proportional to flow. Finally, the identified model is validated based on comparisons of simulations to data on the myocardial perfusion response to conscious exercise that were not used for model identification.