Insu Baek1, Jinsun Hwang1, Jihye Park2, Heasun Kim2, Jong-Sang Park2, Dae Joong Kim3. 1. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 2. Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea. 3. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: daejoongsmc.kim@samsung.com.
Abstract
OBJECTIVE: The local delivery of paclitaxel onto a graft has been reported to prevent neointimal hyperplasia. Because more than half of vascular stenoses occur within 3 cm of the venous anastomosis, this study tested the effectiveness of a paclitaxel coating restricted to both ends of the expanded polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered. METHODS: Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58 μg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel-coated hemodialysis grafts 15 cm in length were surgically implanted between the common carotid artery and external jugular vein in female Landrace pigs. The animals were sacrificed 6 weeks after graft placement. Cross sections of the anastomosis sites were analyzed histomorphometrically to measure the ratio of neointimal hyperplasia to the graft area (H/G ratio) and the percentage of luminal stenosis. The experimental results were compared between grafts coated with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n = 6), and uncoated control grafts (n = 6). RESULTS: The mean ± standard error values of the H/G ratios for the arterial anastomosis were 0.82 ± 0.13 (control), 0.41 ± 0.09 (terminal coating), and 0.21 ± 0.04 (whole coating). The values for the venous anastomosis were 0.82 ± 0.12 (control), 0.39 ± 0.11 (terminal coating), and 0.12 ± 0.03 (whole coating). Compared with the uncoated grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the suppressive effect was less than that of grafts coated with paclitaxel over the entire length. The percentages of luminal stenosis showed similar tendency to the H/G ratios. CONCLUSIONS: Despite a reduced amount of the drug, paclitaxel coating applied to both ends of the ePTFE hemodialysis grafts effectively suppressed neointimal hyperplasia at the sites of anastomosis.
OBJECTIVE: The local delivery of paclitaxel onto a graft has been reported to prevent neointimal hyperplasia. Because more than half of vascular stenoses occur within 3 cm of the venous anastomosis, this study tested the effectiveness of a paclitaxel coating restricted to both ends of the expanded polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered. METHODS: Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58 μg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel-coated hemodialysis grafts 15 cm in length were surgically implanted between the common carotid artery and external jugular vein in female Landrace pigs. The animals were sacrificed 6 weeks after graft placement. Cross sections of the anastomosis sites were analyzed histomorphometrically to measure the ratio of neointimal hyperplasia to the graft area (H/G ratio) and the percentage of luminal stenosis. The experimental results were compared between grafts coated with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n = 6), and uncoated control grafts (n = 6). RESULTS: The mean ± standard error values of the H/G ratios for the arterial anastomosis were 0.82 ± 0.13 (control), 0.41 ± 0.09 (terminal coating), and 0.21 ± 0.04 (whole coating). The values for the venous anastomosis were 0.82 ± 0.12 (control), 0.39 ± 0.11 (terminal coating), and 0.12 ± 0.03 (whole coating). Compared with the uncoated grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the suppressive effect was less than that of grafts coated with paclitaxel over the entire length. The percentages of luminal stenosis showed similar tendency to the H/G ratios. CONCLUSIONS: Despite a reduced amount of the drug, paclitaxel coating applied to both ends of the ePTFE hemodialysis grafts effectively suppressed neointimal hyperplasia at the sites of anastomosis.