Abstract 1928: Coronary Microvascular Remodeling in Cyanotic Congenital Heart Disease.
Background: Basal coronary blood flow is increased in adults with cyanotic congenital heart disease (CCHD), but hyperemic flow and flow reserve remain normal. Since the extramural coronary arteries in CCHD are maximally dilated, we hypothesized that preservation of hyperemic flow and flow reserve resides in the coronary microvasculature.
Methods: To distinguish coronary microvascular adaptive responses to hypoxemia vs cardiac hypertrophy, the apical left ventricular free wall was studied in four patient groups:
Eisenmenger syndrome (hypoxemic, non-hypertrophied);
structurally abnormal hearts with hypertrophy (non-hypoxemic);
structurally normal hearts with hypertrophy (non-hypoxemic); and
structurally normal hearts (non-hypertrophied, non-hypoxemic).
Immunolabeling against anti-smooth muscle α-actin was used on histological sections to examine coronary arterioles (vessels with external diameters of 6 to 50 μm). Morphometric and stereologic analyses determined arteriolar diameter, length, volume and surface densities. Data were log transformed to remove significant right tail skews.
Results: Initial analysis of variance model demonstrated a significant inter-group difference for arteriolar length (p = 0.03) and vessel diameter (p = 0.03), but not for arteriolar volume and surface densities. Sub-analysis by Tukey-Kramer multiple comparison procedure disclosed that total arteriolar length density in Group A was markedly reduced (by 60%) compared to Group B. Lower arteriolar length density in Eisenmenger hearts signified fewer terminal arterioles (6–15 μm) than in structurally abnormal hearts with ventricular hypertrophy (p = 0.01). By contrast, mean arteriolar diameter in Group A was significantly greater (by 34%) than in Group B (p = 0.03). Moreover, a two-sample t-test comparison of Group A with the mean of the other three groups revealed a higher arteriolar diameter in Group A (p = 0.008).
Conclusions: Remodeling of the coronary microcirculatory bed rather than angiogenesis is the key mechanism for preservation of hyperemic flow and flow reserve in CCHD. The increase in vessel diameter compensated for lower arteriolar length density, and was the principal anatomical basis for maintenance of normal flow in CCHD.