Adventitial response to intravascular brachytherapy in a rabbit model of restenosis.
BACKGROUND
The incidence of late major adverse cardiac events (MACE) after coronary brachytherapy is higher than in controls. Because expansive remodeling has been shown to correlate with poor clinical outcome after vascular interventions, we studied adventitial changes after intravascular irradiation in a rabbit model.


METHODS
Twenty normolipidemic rabbits underwent balloon injury in both external iliac arteries. One artery was assigned for subsequent irradiation with a 90Y source (15 Gy or 30 Gy at 0.5 mm in the vessel wall). After four weeks morphometric measurements were made and cell density and collagen amount determined. Staining for Ki67 identified proliferating cells; apoptotic cells were identified by TUNEL staining. Proliferative and apoptotic indices were calculated as the number of respective positive cells/total cell count x100.


RESULTS
The neointimal area decreased to 0.27 +/- 0.3 mm2 after irradiation compared with 0.55 +/- 0.2 mm2 in controls (p=0.007), whereas adventitial area increased from 0.62 +/- 0.3 mm2 to 0.87 +/- 0.3 mm2 (p=0.02). Irradiation reduced both the proliferative (0.95 +/- 2.6 vs. 3.73 +/- 4.7, p=0.026) and apoptotic (0.006 +/- 0.02 vs. 0.107 +/- 0.2, p=0.03) indices in the neointima, but not in the other arterial-wall layers. Collagen amount and arterial remodeling did not differ between the groups. There was no difference between 15 and 30 Gy in any of the parameters, although adventitial thickening was more pronounced in the high-dose group.


CONCLUSIONS
In normolipidemic rabbits, intravascular beta-irradiation after balloon angioplasty is associated with an increase in neoadventitia and a reduction of neointima. It is conceivable that this phenomenon may contribute to the increased incidence of late MACE after vascular brachytherapy.
Wexberg
Paul
P
Department of Cardiology, Division of Internal Medicine II, University of Vienna, Vienna, Austria. paul.wexberg@meduniwien.ac.at
Mück
Konrad
K
Windberger
Ursula
U
Lang
Susanna
S
Osranek
Martin
M
Weidinger
Franz
F
Maurer
Gerald
G
Gottsauner-Wolf
Michael
M
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods*; D002452:Cell Count; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000473:pathology / Q000528:radiation effects; D006083:Graft Occlusion, Vascular / Q000473:pathology* / Q000532:radiotherapy*; D007083:Iliac Artery / Q000473:pathology* / Q000528:radiation effects*; D008297:Male; D011817:Rabbits