Neointimal responses 3 months after (32)P beta-emitting stent placement.
OBJECTIVE
Studies have shown a potential benefit of brachytherapy in preventing restenosis. However, the effects of intravascular radiation on arterial healing have not been well-established. The purpose of this study was to explore the histologic changes following placement of beta-emitting radioactive stents in arteries focusing on intimal responses and endothelialization.


METHODS
3.0-mm beta-emitting (32)P stents (6-microCi and 24-microCi) were placed in rabbit iliac arteries with nonradioactive stents serving as controls. Animals were euthanized at 3 months and histologic assessment, morphometry, and analysis of endothelialization were performed.


RESULTS
The lumen areas of 24-microCi stents (4.24 +/- 0.22 mm(2), p < 0.0007) and 6-microCi stents (4.23 +/- 0.49 mm(2), p < 0.01) were larger than control stents (3.64 +/- 0.44 mm(2)). The mean lumen percent stenosis was 11. 4 +/- 3.0% in the 24-microCi stents (p < 0.007 vs. 6-microCi stents and p < 0.0001 vs. control stents), 18.7 +/- 6.4% in the 6-microCi stents (p < 0.02 vs. control stents), and 25.0 +/- 4.9% in control stents. Neointimal area was least in the 24-microCi stent (54.2% smaller than controls and 42.7% smaller than 6-microCi); the neointimal area of the 6-microCi stents was 20.0% less than controls. The control stent neointima consisted of smooth muscle cells in a proteoglycan and collagen matrix. In contrast, the intima of radioactive stents showed persistent fibrin thrombus with nonconfluent areas of matrix. Actin-positive intimal cell density was reduced with radioactive stenting, but intimal cell proliferation was increased. Evans blue staining, an indicator of increased endothelial permeability, was present on 86 +/- 9% of the stented segment of 6-microCi stents vs. 10 +/- 11% in controls (p < 0.0001). Scanning electron microscopy demonstrated endothelialization of 97 +/- 8% of the intimal surface of control stents; in contrast, the midportion of the 6-microCi stents remained nonendothelialized, and only 33 +/- 15% (p < 0.0001) of the entire stent surface was endothelialized.


CONCLUSIONS
(32)P beta-emitting stents reduce neointimal growth, but healing is incomplete with poor endothelialization at 3 months. Longer-term studies with complete arterial healing are needed to determine whether there is sustained neointimal inhibition by stent-delivered brachytherapy.
Farb
A
A
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Tang
A L
AL
Shroff
S
S
Sweet
W
W
Virmani
R
R
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000502:physiology / Q000528:radiation effects; D007083:Iliac Artery / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D010761:Phosphorus Radioisotopes / Q000627:therapeutic use*; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D011853:Radiobiology; D011879:Radiotherapy Dosage; D015607:Stents; D017539:Tunica Intima / Q000502:physiology / Q000528:radiation effects*; D014945:Wound Healing / Q000502:physiology / Q000528:radiation effects*
D010761:Phosphorus Radioisotopes