Coronary Microvascular Dysfunction in Ischaemic Heart Disease: Lessons From Large Animal Models

The coronary microvasculature is principally responsible for matching coronary blood flow to myocardial demand of oxygen and nutrients. Short-term control of coronary blood flow is achieved via alterations in coronary microvascular tone, whereas long-term control of coronary flow also involves remodelling of the coronary microvasculature, including adjustments in vascular structure, diameter and density. In the past 50 years, considerable research efforts have been directed at understanding the functional and structural coronary microvascular adaptations involved in matching myocardial oxygen supply to demand, and how these mechanisms are affected by various diseases. In this review article, we will discuss our current understanding of the mechanisms underlying the regulation of coronary microvascular tone under healthy physiological conditions and in ischaemic heart disease. We will specifically discuss the role of microvascular dysfunction in obstructive and non-obstructive coronary artery disease, as studied in large animal models and confirmed in human studies. Future research should be directed at further unravelling the disease-specific mechanisms of coronary microvascular dysfunction in order to identify therapeutic targets to improve microvascular function in patients with ischaemic heart disease.