Altered myocardial microvascular 3D architecture in experimental hypercholesterolemia

Background-Experimental hypercholesterolemia (HC) impairs intramyocardial m icrovascular function. However, whether this is associated with alterations in microvascular architecture remained unknown. Using a novel 3D micro-CT scanner, we tested the hypothesis that HC is associated with an alteration in the microvascular architecture. Methods and Results-Pigs were euthanized after 12 weeks of either normal (n =6) or 2% HC (n=6) diet. The hearts were excised and the coronary arteries injected with a radiopaque contrast material. Myocardial samples were scann ed with micro-CT, and 3D images were reconstructed with 21-mum cubic voxels . The myocardium was tomographically subdivided into subepicardium and sube ndocardium, and microvessels (<500 <mu>m in diameter) were counted in situ within each region. In the subendocardium of HC pigs, the intramyocardial d ensity of microvessels was significantly higher than in normal animals (122 1.4+/-199.7 versus 758.3+/-90.8 vessels/cm(3), P<0.05) because of an increa se in the number of microvessels <200 mum in diameter (1214.4+/-199.7 versu s 746.6+/-101.5 vessels/cm(3), P<0.05). The subepicardial vascular density was similar in both groups. Conclusions-HC has differential effects on the spatial density of the suben docardial microvasculature that may play a role in regulation and/or spatia l distribution of myocardial blood flow, This study also demonstrates the f easibility of studying myocardial microvascular architecture with micro-CT in pathophysiological states.