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

Weil BR, Suzuki G, Canty JM Jr. Transmural variation in microvascular remodeling following percutaneous revascularization of a chronic coronary stenosis in swine. Am J Physiol Heart Circ Physiol 318: H696-H705, 2020. First published February 14, 2020; doi:10.1152/ajpheart.00502.2019.-Remodeling of the coronary microcirculation is known to occur distal to a chronic coronary stenosis, but the reversibility of these changes and their functional significance on maximum myocardial perfusion before and after revascularization is unknown. Accordingly, swine instrumented with a chronic silastic stenosis on the left anterior descending coronary artery to produce hibernating myocardium underwent percutaneous coronary intervention (PCI; n = 8) and were compared with animals with a persistent stenosis (n = 8), as well as sham controls (n = 6). Stenotic animals demonstrated an increased subendocardial arteriolar wall thickness to- lumen ratio (37.8 ± 3.3 vs. 28.3 ± 1.3% in sham, P = 0.04), reduced lumen area per arteriole (597 ± 88 vs. 927 ± 113 μm², P = 0.04), and a compensatory increase in arteriolar density (9.4 ± 1.0 vs. 5.3 ± 0.4 arterioles/mm², P < 0.01). As a result, vasodilated flow immediately after PCI was similar to normally perfused remote regions (5.1 ± 1.0 vs. 4.8 ± 0.9 ml·min^-1·g^-1, P = 0.87). When assessed 1-mo after PCI, increases in wall thickness-to-lumen diameter (42.2 ± 3.3%) and reductions in lumen area per arteriole (638 ± 59 μm²) remained unchanged, but arteriolar density returned to normal (5.2 ± 0.5 arterioles/mm²). As a result, maximum subendocardial flow during adenosine declined and was lower than remote regions (2.6 ± 0.3 vs. 5.9 ± 1.1 ml·min^-1·g^-1, P = 0.01). There was no microvascular remodeling in subepicardial arterioles, and maximum perfusion remained unchanged. These data demonstrate that subendocardial microvascular remodeling occurs distal to a chronic epicardial stenosis. The regression of arteriolar density without increases in luminal area may precipitate stress-induced subendocardial ischemia in the absence of a physiologically significant stenosis.