DIFFERENCES IN COMPENSATORY VESSEL ENLARGEMENT, NOT INTIMAL FORMATION, ACCOUNT FOR RESTENOSIS AFTER ANGIOPLASTY IN THE HYPERCHOLESTEROLEMICRABBIT MODEL

Background In de novo human atherosclerosis, compensatory vessel enlar gement limits the effect of intimal plaque formation on lumen narrowin g. We hypothesized that arterial remodeling may also play an important role in determining the chronic lumen size after angioplasty and test ed this hypothesis using the hypercholesterolemic rabbit iliac artery angioplasty model. Methods and Results Morphometric analysis of histol ogical cross-sectional areas of vessels from animals killed immediatel y after angioplasty (acute group, n=11) were compared with the same ar eas from animals killed 4 weeks after the procedure (chronic group, n= 37), when restenosis occurs in this model. The area circumscribed by t he internal elastic lamina (IEL) increased by 20% from acute to 4 week follow-up after angioplasty (acute group, 2.36+/-0.45 mm(2); chronic group, 2.84+/-0.89 mm(2)). Over the same time period, intimal area inc reased by 0.82 mm(2). Despite this increase in intimal area, lumen are a decreased by only 0.34 mm(2) because of the compensatory enlargement of the IEL area. In the chronic group, polynomial regression analysis revealed a quadratic relation between intimal area and lumen area (R( 2)=.35, P<.001). A lumen area of 0.45 mm(2) (the nadir of the quadrati c relation) was used to divide the chronic group into two subgroups: r estenotic (n=21; lumen area, <0.45 mm(2)) and nonrestenotic (n=16; lum en area, >0.45 mm(2)). By definition, there was a significant differen ce in lumen area between the two subgroups (0.15+/-0.15 mm(2) for rest enotic; 0.73+/-0.18 mm(2) for nonrestenotic). Surprisingly, the intima l areas in the two subgroups were virtually identical (2.41+/-0.92 mm( 2) for restenotic, 2.49+/-0.69 mm(2) for nonrestenotic, P=NS). The dif ference in the lumen area between restenotic and nonrestenotic vessels was a result of the significantly greater IEL area in the nonrestenot ic subgroup (3.22+/-0.83 mm(2) for nonrestenotic, 2.56+/-0.84 mm(2) fo r restenotic, P<.05). In both restenotic and nonrestenotic vessels, th e IEL area increased with increases in intimal area. In the restenotic arteries, the slope of this correlation was <1, showing inadequate co mpensatory enlargement for the intimal plaque. In the nonrestenotic ve ssels, the slope was >1, limiting the effect of intimal plaque on lumi nal narrowing. Conclusions These data indicate that the iliac artery i n an atherosclerotic rabbit model compensates for intimal formation af ter angioplasty by vessel enlargement. Furthermore, the degree of vess el enlargement is more important than intimal area in determining the chronic lumen size.