Assessments of microvascular function in organ systems

Abstract

Microvascular disease plays critical roles in the dysfunction of all organ systems, and there are many methods available to assess the microvasculature. These methods can either assess the target organ directly or assess an easily accessible organ such as the skin or retina so that inferences can be extrapolated to the other systems and/or related diseases. Despite the abundance of exploratory research on some of these modalities and their possible applications, there is a general lack of clinical use. This deficiency is likely due to two main reasons: the need for standardization of protocols to establish a role in clinical practice or the lack of therapies targeted toward microvascular dysfunction. Also, there remain some questions to be answered about the coronary microvasculature, as it is complex, heterogeneous, and difficult to visualize in vivo even with advanced imaging technology. This review will discuss novel approaches that are being used to assess microvasculature health in several key organ systems, and evaluate their clinical utility and scope for further development.

Keywords: cardiovascular; endothelial function; imaging; microvascular; organ specific.

Figure 1.

Indirect methods of assessing the microvasculature. Created with BioRender.com and published with permission.

Figure 2.

Anatomy and physiology of the coronary microvasculature. A: terminal arterioles lead into capillaries, which then drain into postcapillary venules and venules. Arterioles can constrict or dilate to direct the blood flow to capillary beds. Capillaries are the main site of gas, solute, and nutrient exchange. Postcapillary venules make up the portion of the microvasculature that is the most reactive to inflammation and permeable to both plasma proteins and leukocytes. Venules, or muscular venules, have smooth muscle fibers present, though not as much as that of the arterioles. B: summary of the size and function of each vessel type found in the microvasculature. *Vessel diameters are approximate values and vary between publications and literature sources. Created with BioRender.com and published with permission.

Figure 3.

Compartmental modeling of radiotracer kinetics to calculate myocardial blood flow (MBF) in positron emission tomography (PET). There are two compartments depicted here: the blood compartment and the tissue compartment. The radiotracer is extracted from the blood to the tissue, and the rate at which this happens is k1. The rate that the radiotracer is washed out back into the blood is k2, and with early imaging, it is assumed that tracer washout and tracer metabolism is negligible. Myocardial blood flow (MBF) is calculated by k1 multiplied by the tracer extraction (E).

Figure 4.

Lung endothelial dysfunction in coronavirus disease-19 (COVID-19). In physiological conditions, nitric oxide (NO) levels are adequate to mediate vasodilation, prevent platelet aggregation, and dampen inflammatory response. There are intact endothelial cell (EC) tight junctions and a protective layer of pericytes around the vasculature. In COVID-19, there is acute endothelial dysfunction: ECs produce large amounts of chemoattractants, cytokines, and adhesion molecules. This leads to leukocyte activation, adhesion, migration through the disrupted tight junctions, and increased vascular permeability. There is also an insufficient production of NO, with resulting increased reactive oxygen species (ROS) levels and vasoconstriction. Viral particles can infect endothelial cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. D-dimer (protein fragments of dissolved blood clots) levels have also been found to be elevated in severe COVID-19 and are associated with worse prognosis.