High-dose external beam irradiation inhibits neointima formation in stented pig coronary arteries.
OBJECTIVE
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
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.
Verheye
S
S
Cardiovascular Translational Research Institute, Middelheim, Antwerp, Belgium.
Coussement
P K
PK
Salame
M Y
MY
Fallahi
P
P
Cui
J
J
Chronos
N A
NA
King
S B
SB
Crocker
I R
IR
Robinson
K A
KA
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D005260:Female; D006321:Heart / Q000528:radiation effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D011879:Radiotherapy Dosage; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure