Khilnani N, Lee M, Winchester P, Zanzonico P, McCaffrey T, Trost D, Jagust M, Binkert B, Sos T
Department of Radiology, New York Hospital-Cornell Medical Center, NY 10021, USA.
Acad Radiol. 1996 Feb;3(2):121-8. doi: 10.1016/s1076-6332(05)80378-2.
Catheter-directed thrombolytic therapy has become an accepted treatment for many vascular occlusions. However, the relative rates of lysis of the different methods of drug administration have not been quantified. We developed an in vitro model to simulate and quantify local lytic therapy of a thrombotic vascular occlusion and tested it by evaluating three catheter-directed lytic strategies.
Seven-centimeter-long segments of 125I-fibrinogen-labeled thrombus made from recently expired human blood from a blood bank were formed in plastic tubes and were placed in a flowing stream of saline. Using multisidehole catheters, the clots were "treated" with intrathrombic saline or urokinase administered by drip infusion or forced injection using identical total doses of drug and volumes of fluid. Using endhole catheters, saline or urokinase was drip infused into the leading edge of the thrombus using the same protocol. A collimated scintillation detector was used to quantify the amount of activity remaining in the thrombus during each experiment, and the resultant time-activity curves for the different trials were compared.
Forced-injection administration of urokinase using a multisidehole catheter produced the fastest lysis, resulting in a half-life of 42 min. The other infusion methods were slower, with half-lives of 153 min for multisidehole urokinase drip infusion, 365 min for endhole urokinase drip infusion, and more than 1,000 min for multisidehole catheter forced injection of saline and multisidehole and endhole saline drip infusion. The differences among these groups were reproducible and statistically significant.
Results suggest that a simple and inexpensive in vitro model simulating lysis of a vascular occlusion can produce reproducible quantitative data. The data demonstrate that forced injection of lytic agents with a multisidehole catheter enhances the rate of thrombolysis and that the enhancement is not primarily attributable to the mechanical effect of this mode of administration.
导管定向溶栓治疗已成为许多血管闭塞性疾病的公认治疗方法。然而，不同给药方法的溶栓相对速率尚未得到量化。我们开发了一种体外模型来模拟和量化血栓性血管闭塞的局部溶栓治疗，并通过评估三种导管定向溶栓策略对其进行了测试。
用来自血库的近期过期人血制成125I-纤维蛋白原标记的血栓，在塑料管中形成7厘米长的节段，并置于流动的盐水中。使用多侧孔导管，用相同总剂量的药物和液体体积，通过滴注或强制注射向血栓内注入生理盐水或尿激酶进行“治疗”。使用端孔导管，按照相同方案将生理盐水或尿激酶滴注到血栓前缘。在每个实验过程中，使用准直闪烁探测器量化血栓中剩余的活性量，并比较不同试验所得的时间-活性曲线。
使用多侧孔导管强制注射尿激酶产生的溶栓速度最快，半衰期为42分钟。其他输注方法较慢，多侧孔尿激酶滴注的半衰期为153分钟，端孔尿激酶滴注的半衰期为365分钟，多侧孔导管强制注射生理盐水以及多侧孔和端孔生理盐水滴注的半衰期超过1000分钟。这些组之间的差异具有可重复性且具有统计学意义。
结果表明，一种简单且廉价的模拟血管闭塞溶栓的体外模型可以产生可重复的定量数据。数据表明，使用多侧孔导管强制注射溶栓剂可提高溶栓速度，且这种提高并非主要归因于这种给药方式的机械效应。
