Thome L M, Gimple L W, Bachhuber B G, McNamara C A, Ragosta M, Gertz S D, Powers E R, Owens G K, Humphries J E, Sarembock I J
Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Circulation. 1998 Nov 24;98(21):2301-6. doi: 10.1161/01.cir.98.21.2301.
A 2-hour infusion of r-hirudin at the time of balloon angioplasty limits restenosis in atherosclerotic rabbits. Because thrombin activity in the vessel wall after angioplasty remains high for 48 to 72 hours, we hypothesized that a second infusion of hirudin at 24 hours would reduce restenosis more than early treatment alone.
Femoral atherosclerosis was induced in 35 rabbits by air desiccation injury and a high-cholesterol diet. At the time of angioplasty, rabbits were randomly assigned to 1 of 4 groups: controls: heparin bolus, saline infusion at 24 hours; early hirudin: hirudin bolus+2 hours' infusion, saline infusion at 24 hours; delayed hirudin: heparin bolus, hirudin infusion+/-bolus at 24 hours; and early+delayed hirudin: hirudin bolus+2 hours' infusion, hirudin infusion+/-bolus at 24 hours. Rabbits were euthanized after 28 days. The early+delayed hirudin treatment group had less loss of minimal lumen diameter by angiography at 28 days. By histomorphometry, cross-sectional area narrowing by plaque was least in the early+delayed treatment group compared with controls (P=0.0001), early hirudin (P=0.01), or delayed hirudin (P=0.001). The early+delayed hirudin group also had a significant reduction in absolute plaque area and an improvement in lumen area compared with the other groups. No differences were observed between treatment groups with respect to the cross-sectional area encompassed by the internal or external elastic laminae.
Combined early+delayed administration of hirudin significantly reduces angiographic restenosis and cross-sectional area narrowing by plaque compared with early or late treatment alone. These results suggest that restenosis after balloon angioplasty is markedly influenced by thrombin-mediated events not only occurring early but also extending beyond the first 24 hours in this model.
在球囊血管成形术时静脉输注重组水蛭素2小时可限制动脉粥样硬化兔的再狭窄。由于血管成形术后血管壁中的凝血酶活性在48至72小时内仍维持在较高水平，我们推测在24小时时再次输注水蛭素比单纯早期治疗能更有效地减少再狭窄。
通过空气干燥损伤和高胆固醇饮食诱导35只兔发生股动脉粥样硬化。在血管成形术时，将兔随机分为4组中的1组：对照组：静脉推注肝素，24小时输注生理盐水；早期水蛭素组：静脉推注水蛭素+输注2小时，24小时输注生理盐水；延迟水蛭素组：静脉推注肝素，24小时输注水蛭素+/-静脉推注；早期+延迟水蛭素组：静脉推注水蛭素+输注2小时，24小时输注水蛭素+/-静脉推注。28天后对兔实施安乐死。早期+延迟水蛭素治疗组在28天时血管造影显示的最小管腔直径损失较小。通过组织形态计量学分析，与对照组（P = 0.0001）、早期水蛭素组（P = 0.01）或延迟水蛭素组（P = 0.001）相比，早期+延迟治疗组中斑块导致的横截面积缩小最少。与其他组相比，早期+延迟水蛭素组的绝对斑块面积也显著减小，管腔面积有所改善。各治疗组在内弹力层或外弹力层所包含的横截面积方面未观察到差异。
与单独早期或晚期治疗相比，早期+延迟联合给予水蛭素可显著降低血管造影再狭窄及斑块导致的横截面积缩小。这些结果表明，在该模型中，球囊血管成形术后的再狭窄不仅受到早期发生而且在最初24小时后仍持续存在的凝血酶介导事件的显著影响。
