Neointimal responses 3 months after P-32 beta-emitting stent placement

Purpose: Studies have shown a potential benefit of brachytherapy in prevent ing restenosis. However, the effects of intravascular radiation on arterial healing have not been well-established. The purpose of this study was to e xplore the histologic changes following placement of beta-emitting radioact ive stents in arteries focusing on intimal responses and endothelialization . Methods and Materials: 3.0-mm beta-emitting P-32 stents (6-mu Ci and 24-mu Ci) 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-mu Ci stents (4.24 +/- 0.22 mm(2),p < 0.0007 ) and 6-mu Ci stents (4.23 +/- 0.49 mm(2),p < 0.01) were larger than contro l stents (3.64 +/- 0.44 mm(2)). The mean lumen percent stenosis was 11.4 +/ - 3.0% in the 24-mu Ci stents (p < 0.007 vs. 6-mu Ci stents and p < 0.0001 vs, control stents), 18.7 +/- 6.4% in the 6-mu Ci stents (p < 0.02 vs. cont rol stents), and 25.0 +/- 4.9% in control stents. Neointimal area was least in the 24-mu Ci stent (54.2% smaller than controls and 42.7% smaller than 6-mu Ci); the neointimal area of the 6-mu Ci stents was 20.0% less than con trols. The control stent neointima consisted of smooth muscle cells in a pr oteoglycan and collagen matrix. In contrast, the intima of radioactive sten ts showed persistent fibrin thrombus with nonconfluent areas of matrix. Act in-positive intimal cell density was reduced with radioactive stenting, but intimal cell proliferation was increased. Evans blue staining, an indicato r of increased endothelial permeability, was present on 86 +/- 9% of the st ented segment of 6-mu Ci stents vs. 10 +/- 11% in controls (p < 0.0001). Sc anning electron microscopy demonstrated endothelialization of 97 +/- 8% of the intimal surface of control stents; in contrast, the midportion of the 6 -mu Ci stents remained nonendothelialized, and only 33 +/- 15% (p < 0.0001) of the entire stent surface was endothelialized. Conclusions: 32P beta-emitting stents reduce neointimal growth, but healing is incomplete with poor endothelialization at 3 months. Longer-term studie s with complete arterial healing are needed to determine whether there is s ustained neointimal inhibition by stent-delivered brachytherapy. (C) 2000 E lsevier Science Inc.