The Influence of Lesion Length on Intimal Hyperplasia after Fogarty Balloon Injury in the Rabbit Carotid Artery: Role of Endothelium

After balloon angioplasty, retarded endothelial cell recoverage of the injured segment may lead to enhanced intimal hyperplasia. We tested the hypothesis that long lesions result in more intimal hyperplasia than short lesions due to a prolonged time to complete endothelial cell recoverage. A 2-french Fogarty balloon was used to create 2.5- and 5-cm-long lesions in the rabbit carotid artery. After termination, the injured arteries (n = 9 for all groups) were serially processed for histochemistry. Endothelial cell coverage was assessed with an antibody to CD31 and cell proliferation with a monoclonal antibody to Ki-67 nuclear antigen. The intimal hyperplasia cross-sectional area was measured morphometrically. All data are mean +/- SEM. At 21 days, endothelial cell recoverage was almost complete in the 2.5-cm lesions. In the 5-cm lesions, endothelial cell recoverage was 66 +/- 6% in the middle segments (p = 0.04, 2.5 vs. 5 cm) and 100% at the cranial and caudal ends of the lesion. At 42 days, endothelial cell coverage had increased to 81 +/- 7% in the middle segments of the 5-cm lesions. The intimal hyperplasia area was similar in the 2.5- and the 5-cm lesions both at 21 days (0.19 +/- 0.02 and 0.20 +/- 0.01 mm2, respectively) and 42 days (0.27 +/- 0.02 and 0.26 +/- 0.03 mm2, respectively). The increase in intimal hyperplasia from 21 to 42 days was significant for both lesion lengths (p = 0.004). At 21 days, intimal proliferation was similar for the 2.5- and 5-cm lesions. After 42 days postinjury, intimal proliferation had decreased (p < 0.001) equally for both lesion lengths. Earlier recoverage by endothelium in the 2.5-cm lesions did not inhibit intimal hyperplasia compared to the 5-cm lesions which were still incompletely reendothelialized. We conclude that in the rabbit, rapid endothelial cell recoverage of Fogarty balloon-injured arteries may not limit intimal hyperplasia in the center of the lesion. It is conceivable that the inability of regenerated endothelium to inhibit intimal hyperplasia is due to its initially dedifferentiated and possibly dysfunctional phenotype.