IN-VITRO MODEL TO EVALUATE THE RELATIVE EFFICACY OF CATHETER-DIRECTEDTHROMBOLYTIC STRATEGIES

Rationale and Objectives. Catheter-directed thrombolytic therapy has b ecome an accepted treatment for many vascular occlusions, However, the relative rates of lysis of the different methods of drug administrati on have not been quantified. We developed an in vitro model to simulat e and quantify local lyric therapy of a thrombotic vascular occlusion and tested it by evaluating three catheter-directed lytic strategies. Methods. Seven-centimeter-long segments of I-125-fibrinogen-labeled th rombus made from recently expired human blood from a blood bank were f ormed in plastic tubes and were placed in a flowing stream of saline. Using multisidehole catheters, the clots were ''treated'' with intrath rombic saline or urokinase administered by drip infusion or forced inj ection using identical total doses of drug and volumes of fluid. Using endhole catheters, saline or urokinase was drip infused into the lead ing edge of the thrombus using the same protocol, A collimated scintil lation detector was used to quantify the amount of activity remaining in the thrombus during each experiment, and the resultant time-activit y curves for the different trials were compared. Results. Forced-injec tion administration of urokinase using a multisidehole catheter produc ed the fastest lysis, resulting in a half-life of 42 min. The other in fusion methods were slower, with half-lives of 153 min for multisideho le urokinase drip infusion, 365 min for endhole urokinase drip infusio n, and more than 1,000 min for multisidehole catheter forced injection of saline and multisidehole and endhole saline drip infusion. The dif ferences among these groups were reproducible and statistically signif icant. Conclusion. Results suggest that a simple and inexpensive in vi tro model simulating lysis of a vascular occlusion can produce reprodu cible quantitative data, The data demonstrate that forced injection of lytic agents with a multisidehole catheter enhances the rate of throm bolysis and that the enhancement is not primarily attributable to the mechanical effect of this mode of administration.