Downstream Influence of Coronary Stenoses on Microcirculatory Remodeling

Abstract

Objective: Inducible myocardial ischemia is influenced by contributions of both the epicardial artery and the coronary microcirculation. Experimental studies have found adverse microcirculatory remodeling to occur downstream of severe coronary stenoses. Coronary physiology studies in patients contradict the experimental findings, as the minimal microvascular resistance is not modified by stenoses. The objective was to determine whether microcirculatory remodeling occurs downstream of coronary stenoses in the human coronary circulation. Approach and Results: Myocardium corresponding to 115 coronary arteries of 55 deceased patients was investigated. Histopathologic staining of the microcirculation was performed using antibodies against SMA-α (smooth muscle actin-α) and CD31, to stain arterioles and capillaries, respectively. The following parameters were analyzed: ratio between lumen and vesel area, ratio between lumen and vessel diameter (both ratios for arterioles of <40, 40–100, and 100–200 µm diameter), arteriolar density, and capillary density. From the 55 patients, 32 pairs of an unobstructed coronary artery and a coronary artery with a stenosis were formed. No statistically significant differences between any of the microcirculatory parameters were found. A confirmatory unpaired analysis compared 3 groups: (1) coronary arteries in patients without coronary artery disease (n=53), (2) unobstructed coronary arteries in patients with a stenosis in one of the other coronary arteries (n=23), and (3) coronary stenoses (n=39). No statistically significant differences were observed between the groups. Conclusions: The microcirculation distal to noncritical stenoses does not undergo structural remodeling in the human coronary circulation.

Transmural variation in microvascular remodeling following percutaneous revascularization of a chronic coronary stenosis in swine

“…Recent postmortem human studies have failed to identify microvascular remodeling distal to moderate coronary stenoses (10). These observations are consonant with the lack of struc-tural arteriolar remodeling seen in some studies with chronic hibernating myocardium from a fixed (but less severe) LAD stenosis.…”

“…Our values of anatomic stenosis severity are higher and maximal perfusion much lower than in studies without structural arteriolar remodeling (27), which may be responsible for the different findings. Moreover, the localization of structural remodeling in the subendocardium as well as its relation to functional stenosis severity rather than anatomic severity may explain why de Waard et al (10) found no arteriolar remodeling or changes in capillary or arteriolar density in postmortem analysis of patients with chronic coronary stenoses of moderate severity (average diameter stenosis 70%).…”

“…However, the contribution of microvascular dysfunction to impairments in myocardial perfusion in this setting are unclear. Clinical studies examining microcirculatory resistance after revascularization of a chronic stenosis are discordant as to whether the poststenotic region has a normal or increased minimal microvascular resistance (1,7,10). Besides poten-tially exacerbating the impairment in CFR caused by the presence of a stenosis, persistence of coronary microvascular remodeling after revascularization may adversely affect myocardial perfusion, potentially leading to recurrent angina and delayed recovery of ventricular function despite successful restoration of epicardial artery patency (8).…”

Coronary Microvascular Dysfunction

“…The findings showed no microcirculatory remodeling distal to noncritical stenoses, validating the rationale for invasive or noninvasive physiology-derived indices, such as fractional flow reserve, and that microvascular resistance at maximal hyperemia is similar regardless of the presence or absence of a stenosis. 19,20 The endothelium plays a pivotal role in modulating vascular tone by synthesizing and liberating endotheliumderived relaxing factors, including vasodilator prostaglandins, NO, and endothelium-dependent hyperpolarization (EDH) factors in a distinct vessel size-dependent manner; NO predominantly mediates vasodilatation of relatively large, conduit vessels (eg, epicardial coronary arteries), while EDH factors in small resistance vessels (eg, coronary microvessels; Figure 1). 21,22 Endothelium-dependent CMD can be attributed to reduced production or action of these relaxing mediators.…”

“…A comprehensive invasive assessment of CMD by functional coronary angiography is safe, feasible, and of diagnostic value to better differentiate between endothelium-dependent and independent CMD. 3,10,13,18 An autopsy study by de Waard et al 19 of patients without structural or infiltrative myocardial disease who had undergone coronary angiography within 2 years before death was performed to examine whether structural alterations occurred in the coronary microcirculation downstream of epicardial coronary stenoses. The findings showed no microcirculatory remodeling distal to noncritical stenoses, validating the rationale for invasive or noninvasive physiology-derived indices, such as fractional flow reserve, and that microvascular resistance at maximal hyperemia is similar regardless of the presence or absence of a stenosis.…”