In vitro model to evaluate the relative efficacy of catheter-directed thrombolytic strategies

Abstract

Rationale and objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.