Chung Thomas L, Pumplin David W, Holton Luther H, Taylor Jesse A, Rodriguez Eduardo D, Silverman Ronald P
Baltimore, Md. From the Division of Plastic and Reconstructive Surgery, University of Maryland Medical Center, and Department of Anatomy and Neurobiology, University of Maryland School of Medicine.
Plast Reconstr Surg. 2007 Oct;120(5):1281-1288. doi: 10.1097/01.prs.0000279327.75083.ae.
Recent clinical trials involving patients with acute coronary syndromes have demonstrated significant reduction in the progression of coronary artery thrombosis using a regimen of aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. Acute coronary syndromes and free tissue transfer are similar pathophysiologically in that they both involve endothelial injury, thrombosis, and ischemia. In this study, the authors investigate tirofiban, combined with aspirin and heparin, for the prevention of microsurgical anastomotic thrombosis in a thrombogenic rat model.
Using a randomized, controlled, double-blind experimental design, 80 thrombogenic anastomoses were performed on rat femoral arteries (n = 40) and veins (n = 40). Preoperatively, each rat received one of four treatment regimens: aspirin and heparin (regimen 1), aspirin and heparin plus tirofiban (regimen 2), tirofiban alone (regimen 3), or isotonic saline (control) (regimen 4). Vessels were assessed for patency at 5, 15, 30, and 120 minutes after reperfusion and then harvested for microscopic analysis.
At 120 minutes after reperfusion, regimen 1 had an arterial and venous patency rate of 80 percent and 70 percent, respectively, whereas the vessel patency rate for regimen 2 was 100 percent. The difference between regimens 1 and 2 was not statistically significant. Regimens 3 and 4 had vessel patency rates of 40 percent or less. The aspirin/heparin and aspirin/heparin/tirofiban groups both demonstrated significantly improved vessel patency and significantly less thrombotic occlusion compared with controls.
Combination therapy with aspirin, heparin, and tirofiban significantly increases arterial and venous patency and decreases anastomotic thrombus formation in thrombogenic anastomoses in rats. The role of glycoprotein IIb/IIIa inhibitors in microsurgery warrants further investigation.
近期涉及急性冠状动脉综合征患者的临床试验表明，使用阿司匹林、肝素和糖蛋白IIb/IIIa抑制剂替罗非班的治疗方案可显著降低冠状动脉血栓形成的进展。急性冠状动脉综合征和游离组织移植在病理生理上相似，因为它们都涉及内皮损伤、血栓形成和缺血。在本研究中，作者研究了替罗非班联合阿司匹林和肝素在血栓形成大鼠模型中预防显微外科吻合口血栓形成的作用。
采用随机、对照、双盲实验设计，在大鼠股动脉（n = 40）和静脉（n = 40）上进行80次血栓形成吻合术。术前，每只大鼠接受四种治疗方案之一：阿司匹林和肝素（方案1）、阿司匹林和肝素加替罗非班（方案2）、单独使用替罗非班（方案3）或等渗盐水（对照）（方案4）。在再灌注后5、15、30和120分钟评估血管通畅情况，然后收获血管进行显微镜分析。
再灌注后120分钟，方案1的动脉和静脉通畅率分别为80%和70%，而方案2的血管通畅率为100%。方案1和方案2之间的差异无统计学意义。方案3和方案4的血管通畅率为40%或更低。与对照组相比，阿司匹林/肝素组和阿司匹林/肝素/替罗非班组均显示血管通畅显著改善，血栓闭塞显著减少。
阿司匹林、肝素和替罗非班联合治疗可显著提高大鼠血栓形成吻合术中动脉和静脉的通畅率，并减少吻合口血栓形成。糖蛋白IIb/IIIa抑制剂在显微外科中的作用值得进一步研究。
