Differential remodeling after balloon overstretch injury and either beta- or gamma-intracoronary radiation of porcine coronary arteries.
BACKGROUND
Restenosis is a consequence of both neointimal hyperplasia and vessel remodeling. Prior studies have shown that intracoronary radiation (IR) prevents neointima accumulation, but its contribution to vessel remodeling is unknown. The purpose of this study was to evaluate the effect of IR on differential vascular remodeling after balloon angioplasty in porcine coronary arteries.


METHODS
A total of 20 juvenile swine (30 coronary arteries) were subjected to overstretch balloon injury (BI) followed by IR with either beta- or gamma-radiation ((90)Y or (192)Ir). After 2 weeks following treatment, serial tissue sections were perfusion fixed and stained by hematoxylin and eosin (H&E), Verhoeff von Giesson (VVG), or Masson Trichrome. Adventitial area (AA), lumen area (LA), vessel area (VA), intimal area (IA), and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis. The vessel circumference was divided into two regions containing (1) the undisrupted region (UReg) with the undisrupted arc of media and internal elastic lamina (IEL) and (2) the disrupted region (DReg) with the disrupted arc between the medial tears. Quantitative regional analysis was performed by (1) measuring the IEL to define the UReg, (2) calculating the area of the UReg with the perimeter value derived from measurement of the IEL, and (3) calculating the DReg as follows: LA+IA-UReg. Immunohistochemical smooth muscle cell alpha-actin and Masson Trichrome were quantified by digital image analysis.


RESULTS
The IA/FL was significantly smaller following treatment with (90)Y or (192)Ir vs. control (P<.01). A smaller AA was obtained following IR with both beta- and gamma-sources vs. control (P<.01). The UReg calculation was smaller in the irradiated arteries as compared to control (beta: 2.3+/-0.4 mm(2), gamma: 2.1+/-0.5 mm(2), P<.01 vs. control; control: 3.6+/-0.7 mm(2)). In contrast, the DReg was increased following IR, as demonstrated by the FL and the calculated area of the injured segment (control: 2.7+/-0.5 mm(2); beta: 5.5+/-1.1 mm(2), gamma: 5.5+/-1.1 mm(2), P<.01 vs. control). Adventitial alpha-actin positive cell density (CD) was decreased after IR; however, the collagen density was similar. In contrast, the neointimal collagen density in the injured segment was significantly decreased following IR.


CONCLUSIONS
We consider that the global arterial remodeling after IR is a heterogeneous process that includes the absence of retraction in an UReg and a positive remodeling in the DReg as shown in the porcine coronary model. These changes in adventitia and neointima appear to contribute to differential vascular remodeling caused by IR in injured vessels.
Cottin
Y
Y
Cardiovascular Research Institute, Washington Hospital Center, 110 Irving Street, NW Suite 4B-1, Washington, DC 20010, USA.
Kollum
M
M
Chan
R C
RC
Kim
H
H
Bhargava
B
B
Vodovotz
Y
Y
Waksman
R
R
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001918:Brachytherapy; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology / Q000528:radiation effects; D005352:Fibromuscular Dysplasia / Q000473:pathology*; D007496:Iridium Radioisotopes; D012008:Recurrence; D017539:Tunica Intima / Q000473:pathology / Q000528:radiation effects*; D015021:Yttrium Radioisotopes
D007496:Iridium Radioisotopes; D015021:Yttrium Radioisotopes