Baumbach A, Oberhoff M, Bohnet A, Miljak T, Herdeg C, Horch B, Blessing E, Kunert W, Haase K K, Karsch K R
Department of Medicine, University of Tübingen, Germany.
Cathet Cardiovasc Diagn. 1997 Jul;41(3):303-7. doi: 10.1002/(sici)1097-0304(199707)41:3<303::aid-ccd11>3.0.co;2-o.
Local drug delivery can be achieved with active injection systems or passive contact of a compound with the arterial wall. The Dispatch catheter allows for passive diffusion of drugs from drug compartments while preserving blood flow through the central conduit. The aim of this study was to investigate whether a reduction in neointima formation can be achieved by local delivery of a limited amount of a highly concentrated solution of the low-molecular-weight heparin Reviparin. In 16 New Zealand white rabbits, successful balloon dilatation was performed in both iliac arteries, followed by local delivery of 4 ml Reviparin (1,000 IU/ml). The arteries were harvested at 7, 28, or 56 d following the procedure. The intimal cell layers increased substantially between 7 and 28 d following balloon dilatation with or without local drug delivery. The medial cell layers showed only a little increase. Proliferation of smooth muscle cells reached an early peak after 7 d, with a significantly higher proliferation index following local delivery. The maximum amount of macrophages in the intima and media was detected after 28 d. The lumen area decreased with time and was 0.6 +/- 0.7 mm2 in the local delivery group at 56 d compared with 0.5 +/- 0.5 mm2 in the control group. In conclusion, local delivery of Reviparin with the Dispatch catheter is safe and feasible. However, the infusion of highly concentrated low-molecular-weight heparin over a short period of time did not result in a reduction of neointima formation and restenosis following balloon dilatation in the rabbit iliac artery.
局部药物递送可通过主动注射系统或使化合物与动脉壁被动接触来实现。Dispatch导管允许药物从药物隔室被动扩散,同时保持通过中央导管的血流。本研究的目的是调查通过局部递送有限量的高浓度低分子量肝素Reviparin溶液是否可以减少新生内膜形成。在16只新西兰白兔中,对双侧髂动脉进行成功的球囊扩张,然后局部递送4ml Reviparin(1000IU/ml)。在该操作后7、28或56天收获动脉。无论有无局部药物递送,在球囊扩张后7至28天内,内膜细胞层数均显著增加。中膜细胞层仅略有增加。平滑肌细胞增殖在7天后达到早期峰值,局部递送后增殖指数显著更高。在28天后检测到内膜和中膜中巨噬细胞的最大数量。管腔面积随时间减小,局部递送组在56天时为0.6±0.7mm2,而对照组为0.5±0.5mm2。总之,使用Dispatch导管局部递送Reviparin是安全可行的。然而,在短时间内输注高浓度低分子量肝素并未导致兔髂动脉球囊扩张后新生内膜形成和再狭窄的减少。