Department of Physiology and Anatomy, University of North Texas Health Science Center, USA.
Department of Physiology and Anatomy, University of North Texas Health Science Center, USA.
J Mol Cell Cardiol. 2024 May;190:82-91. doi: 10.1016/j.yjmcc.2024.04.008. Epub 2024 Apr 11.
The coronary circulation has the inherent ability to maintain myocardial perfusion constant over a wide range of perfusion pressures. The phenomenon of pressure-flow autoregulation is crucial in response to flow-limiting atherosclerotic lesions which diminish coronary driving pressure and increase risk of myocardial ischemia and infarction. Despite well over half a century of devoted research, understanding of the mechanisms responsible for autoregulation remains one of the most fundamental and contested questions in the field today. The purpose of this review is to highlight current knowledge regarding the complex interrelationship between the pathways and mechanisms proposed to dictate the degree of coronary pressure-flow autoregulation. Our group recently likened the intertwined nature of the essential determinants of coronary flow control to the symbolically unsolvable "Gordian knot". To further efforts to unravel the autoregulatory "knot", we consider recent challenges to the local metabolic and myogenic hypotheses and the complicated dynamic structural and functional heterogeneity unique to the heart and coronary circulation. Additional consideration is given to interrogation of putative mediators, role of K and Ca channels, and recent insights from computational modeling studies. Improved understanding of how specific vasoactive mediators, pathways, and underlying disease states influence coronary pressure-flow relations stands to significantly reduce morbidity and mortality for what remains the leading cause of death worldwide.
冠状动脉循环具有在广泛的灌注压范围内维持心肌灌注恒定的固有能力。压力-流量自动调节现象对于限制血流的动脉粥样硬化病变至关重要，这些病变会降低冠状动脉驱动压并增加心肌缺血和梗死的风险。尽管经过了半个多世纪的专门研究，但对自动调节机制的理解仍然是当今该领域最基本和最具争议的问题之一。本文旨在强调当前关于决定冠状动脉压力-流量自动调节程度的途径和机制之间复杂相互关系的知识。我们小组最近将决定冠状动脉血流控制的基本决定因素的交织性质比作象征性地无法解决的“戈尔迪乌姆结”。为了进一步努力解开自动调节的“结”，我们考虑了对局部代谢和肌源性假说的最新挑战，以及心脏和冠状动脉循环所特有的复杂动态结构和功能异质性。还考虑了对假定介质、K 和 Ca 通道的作用以及来自计算模型研究的最新见解的探讨。对特定血管活性介质、途径和潜在疾病状态如何影响冠状动脉压力-流量关系的更好理解，有望显著降低全球范围内仍是主要死因的发病率和死亡率。
