Arterial remodeling at the reference site after angioplasty in the atherosclerotic rabbit model

Recent studies suggest that arterial remodeling plays an important role in restenosis and that remodeling at the reference site may also occur. To assess the chronic effect of the reference site remodeling on angioplasty results, we evaluated reference site remodeling in an experimental atherosclerotic restenosis model. Histological sections of iliac stenoses and their associated proximal reference segments from 50 atherosclerotic rabbits killed 4 weeks after angioplasty were analyzed. Lumen area (LA), external elastic lamina area (EEL), and intimal plus medial areas (I+M) were measured at the lesion (L) and reference (R) sites. Angiography was performed preangioplasty, immediately postangioplasty, and 4 weeks postangioplasty. Restenosis was defined as an angiographic loss/gain ratio of greater than 50% at follow-up angiography. Twenty-three lesions were restenotic (R+) and 32 were not (R-). There was no difference in reference site diameters (RD) between these two groups at the time of angioplasty. However, RDs were significantly smaller in the R+ group than in the R- group (1.24+/-0.18 versus 1.52+/-0.28 mm, n=55, P<.01) at 4-week follow-up. Morphometric analysis also showed a smaller LA(R) in the R+ group (0.85+/-0.27 versus 1.06+/-0.37 mm2, n=55, P<.02), whereas there was no difference in I+M(R) between the two groups. EEL(R) significantly correlated with EEL(L), LA(R), and I+M(R) in both groups combined (r=.53, n=55, P<.0001; r=.62, n = 55, P < .0001; and r = .86, n = 55, P < .0001, respectively). Remodeling can favorably and unfavorably affect both the lesion and the reference sites and appears to occur in parallel and proportionately at both sites. These data suggest that angiographic measurement of late percent stenosis using reference site diameters may lead to an underestimation of the percent luminal narrowing in restenotic lesions because unfavorable remodeling occurs in both the lesion and reference sites in restenotic vessels.