Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique.
OBJECTIVE
The objective of this study was to examine the quantitative response of the adventitial vasa vasorum to balloon-induced coronary injury.


BACKGROUND
Recent attention has focused on the role of vasa 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 vasa vasorum in normal and balloon injured porcine coronary arteries. We also studied the spatial growth of vasa vasorum in regions of neointimal formation. A 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 a low-viscosity, radiopaque liquid polymer compound. Normal and injured coronary segments were scanned using a 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 a voxel size of 21 microm.


RESULTS
Normal vasa vasorum originated from the coronary artery lumen, principally at large branch points. Two different types of vasa were found and classified as first-order or second-order according to location and direction. In balloon-injured coronary arteries, adventitial vasa 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 vasa spatial distribution was disrupted compared with normal vessels, with proportionally more second-order vasa vasorum. The diameters of first-order and second-order vasa 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 vasa vasorum was proportional to vessel stenosis (r = 0.81, p = 0.0001). Although the total number of vasa was increased after injury, the total vascular area comprised of vasa 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.
Kwon
H M
HM
Department of Internal Medicine and Cardiovascular Diseases, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Sangiorgi
G
G
Ritman
E L
EL
Lerman
A
A
McKenna
C
C
Virmani
R
R
Edwards
W D
WD
Holmes
D R
DR
Schwartz
R S
RS
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D003251:Constriction, Pathologic; D003331:Coronary Vessels / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D013552:Swine; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014651:Vasa Vasorum / Q000473:pathology*