Adventitial vas vasorum in balloon-injured coronary arteries: Visualization and quantitation by microscopic three-dimensional computed tomography technique

Objectives. The objective of this study was to examine the quantitative response of the adventitial vas vasorum to balloon-induced coronary injury. Background. Recent attention has focused on the role of vas vasorum in atherosclerotic and restenotic coronary artery disease. However, the three-dimensional anatomy of these complex vessels is largely unknown, especially after angioplasty injury. The purpose of this study was to visualize and quantitate three-dimensional spatial patterns of vas vasorum in normal and balloon injured porcine coronary arteries. We also studied the spatial growth of vas vasorum in regions of neointimal formation. novel imaging technique, microscopic computed tomography, was used for these studies. Methods. Four pigs were killed 28 d after coronary balloon injury, and four pigs with uninjured coronary arteries served as normal controls. The coronary arteries were injected with low-viscosity, radiopaque liquid polymer compound. Normal and injured coronary segments were scanned using microscopic computed tomography technique. Three-dimensional reconstructed maximum intensity projection and voxel gradient shading images were displayed at different angles and voxel threshold values, using image analysis software. For quantitation, seven to 10 cross-sectional images (40 normal and 32 balloon injured cross-sections) were captured from each specimen at voxel size of 21 μm. Results. Normal vas vasorum originated from the coronary artery lumen, principally at large branch points. Two different types of vas were found and classified as first-order or second-order according to location and direction. In balloon-injured coronary arteries, adventitial vas vasorum density was increased (3.16 ± 0.17/mm2 vs. 1.90 ± 0.06/mm2, p = 0.0001; respectively), suggesting neovascularization by 28 d after vessel injury. Also, in these injured arteries, the vas spatial distribution was disrupted compared with normal vessels, with proportionally more second-order vas vasorum. The diameters of first-order and second-order vas were smaller in normal compared with balloon-treated coronary arteries (p = 0.012 first-order; p < 0.001, second-order; respectively). The density of newly formed vas vasorum was proportional to vessel stenosis (r = 0.81, p = 0.0001). Although the total number of vas was increased after injury, the total vascular are comprised of vas was significantly reduced in injured vessels compared with normals (3.83 ± 0.20% to 5.42 ± 0.56%, p = 0.0185). Conclusions. Adventitial neovascularization occurs after balloon injury. The number of new vessels is proportional to vessel stenosis. These findings may hold substantial implications for the therapy of vascular disease and restenosis.