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Human Internal Mammary Artery (IMA) Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis
Published on: May 9, 2012
High-dose external beam irradiation inhibits neointima formation in stented pig coronary arteries
S Verheye1, P K Coussement, M Y Salame
1Cardiovascular Translational Research Institute, Middelheim, Antwerp, Belgium.
Purpose:
To evaluate high-dose external beam irradiation (EBRT) in a pig coronary stent preparation because low and intermediate-dose EBRT failed to show inhibition of neointima formation in stented animal models.
Methods And Materials:
Thirty-five stents were implanted in the coronary arteries of 17 pigs. Seven pigs were exposed to a single dose of 21 Gy EBRT immediately after stenting. Ten stented, nonirradiated pigs served as controls. After 4 weeks, the study arteries and myocardium were examined by light and scanning electron microscopy.
Results:
Compared with controls, 21 Gy EBRT resulted in a larger lumen area (7.57 +/- 1.67 mm2 vs. 4.00 +/- 1.63 mm2, p <0.001), a smaller neointima area (0.47 +/- 0.43 mm2 vs. 3.36 +/- 2.26 mm2, p <0.001) and a smaller maximal intimal thickness (0.16 +/- 0.09 mm vs. 0.68 +/- 0.31 mm, p <0.001). Unresorbed intramural hemorrhages and adherent mural thrombi were present in the irradiated vessels, which also showed incomplete re-endothelialization. The irradiated hearts demonstrated diffuse interstitial and perivascular inflammation and fibrosis.
Conclusions:
EBRT at 21 Gy to the entire heart significantly inhibited neointima formation in stented pig coronary arteries but also resulted in incomplete re-endothelialization, myocardial inflammation, and fibrosis. Improvements in localization and delivery techniques are required to allow clinical implementation of this technique.
