Forceful pulsatile local infusion of enzyme accelerates thrombolysis: in vivo evaluation of a new delivery system

Abstract

Forceful local pulsatile infusion of fibrinolytic enzyme disrupts thrombi, increases clot surface area, and thereby hastens enzyme action compared with conventional constant infusion methods, which are time consuming and therefore expensive. Prolonged thrombolytic therapy is associated with increased patient morbidity. A prototype for a clinically applicable pulsatile jet infusion system for accelerating thrombolysis was designed. The system is adaptable to standard angiographic catheters and techniques. The core of the system is a reciprocating syringe pump that delivers small volumes of thrombolytic enzyme in short, rapid, frequent pulses at high exit-jet velocity through any side-hole catheter (the smallest used was a 3-F catheter). Comparison of this system with a constant infusion system was made in vivo in a 48-hour-old thrombus model in rabbit inferior vena cava (IVC). One hour of lysis by streptokinase was conducted with each of the methods. In the first experiment, the IVC thrombi were left intact before chemical lysis. Pulsatile infusion lysed 61% of the thrombus by weight in an hour, whereas constant infusion lysed only 15% (P less than .001). In the second experiment, IVC thrombi were subjected initially to standardized mechanical perturbation by a guide wire before chemical lysis. In the latter experiment, pulsatile infusion lysed 54% of the thrombus by weight, and constant infusion lysed only 26% (P less than .005). The difference in percentage of lysis by weight between pulsatile infusion groups in the two experiments (61% vs 54%) was not significant (P greater than .1). The same was true of the difference between the two constant infusion groups (26% vs 15%, P greater than .05). The effect of initial perturbation of the thrombus by a guide wire appears to be less important than the thrombus disruption and accelerated thrombolysis caused by the pulsatile delivery system. No angiographic or macroscopically visible damage was seen in any IVC. Accelerated thrombolysis may reduce the expense, duration, and morbidity associated with conventional constant infusion methods.