Early cell loss after angioplasty results in a disproportionate decrease in percutaneous gene transfer to the vessel wall

Acute cell loss has been documented following angioplasty of normal rat and rabbit arteries. Here we analyzed the effects of balloon injury intensity on early cellular loss in single- and double-injury models and how it influ ences the efficiency of percutaneous gene delivery to the vessel wall. Rabb its underwent bilateral iliac angioplasties (n = 52) with 2.5-mm (balloon-t o-artery [B/A] ratio, 1.08 to 1.13) and 3.0-mm (B/A ratio, 1.29 to 1.34) ba lloons. In the single-injury model, the 3.0-mm balloon induced a 61% reduct ion in medial cellularity at 3 days postinjury (p < 0.001) while the 2.5-mm balloon did not produce significant cell loss. In the double-injury model, the effects were more pronounced, with 35% (p < 0.01) and 91% (p < 0.001) reductions in medial cellularity at 3 days with the 2.5- and 3.0-mm balloon s, respectively, but neointimal cellularity was decreased only with the 3.0 -mm balloon (37% reduction, p = 0.025). Adenovirus-mediated P-galactosidase gene delivery with a channel balloon (n = 24) revealed that larger balloon -to-artery ratios decreased both absolute levels and relative frequencies o f transgene expression in the vessel wall. In the single-injury model, gene transfer efficiency was 4.2 +/- 1.1 and 1.3 +/- 0.25% (p < 0.05) for the s mall and large balloons, respectively. In the double-injury model, gene tra nsfer efficiency was 6.6 +/- 1.6 and 2.3 +/- 0.8% (p < 0.05) in the neointi ma and 4.1 +/- 1.2 and 2.6 +/- 1.2% (p = NS) in the media for the small and large balloon, respectively. We conclude that early cell loss is dependent on the intensity of the injury in both single- and double-injury models of balloon angioplasty, with greater frequencies of cell loss occurring in th e media than in the neointima. In both models, larger balloon-to-artery rat ios result in disproportionate reductions in percutaneous adenovirus-mediat ed gene delivery.