CATHETER-BASED LOCAL THROMBOLYSIS WITH UROKINASE - COMPARATIVE EFFICACY OF INTRALUMINAL CLOT LYSIS WITH CONVENTIONAL UROKINASE INFUSION TECHNIQUES IN AN IN-VIVO PORCINE THROMBUS MODEL

Local delivery of urokinase directly to the site of intraluminal clot using catheter-based technology has recently been introduced as a new technique to treat intracoronary thrombus and thrombus-containing sten oses, The purpose of this study was to compare the efficacy of urokina se therapy administered by local drug-delivery catheters with conventi onal urokinase-infusion techniques in dissolving intraluminal clot and intramurally depositing drug at the site of arterial injury in an in vivo porcine model. Five techniques of urokinase administration were s tudied in 65 pigs, including intravenous systemic bolus (1,000,000 uni ts), guiding catheter infusion (500,000 units), local intraluminal inf usion with a Roubin catheter (150,000 units), local infusion by the Di spatch catheter (150,000 units), and local delivery by the hydrogel-co ated balloon (700 units). All five techniques were initially compared with respect to the quantity of intraluminal lysis of I-123-fibrinogen -labeled thrombus in an in vivo thrombus model. Conventional balloon a ngioplasty was also assessed in this model as a nonpharmacologic, mech anical control. In addition, all five techniques were compared with re spect to the quantity and efficiency of intramural urokinase depositio n at coronary angioplasty sites. In the in vivo thrombolysis experimen ts, the quantity of artificial clot lysis measured 8.8% for systemic t herapy, 20.8% for guiding catheter infusion, 25.2% for Roubin catheter infusion, 62.8% for Dispatch catheter infusion, 98.8% for hydrogel ba lloon delivery, and 53.6% for conventional balloon angioplasty. Both t he Dispatch catheter and the hydrogel balloon resulted in more clot ly sis than the systemic, guiding catheter, or Roubin catheter approaches (P < 0.05). In comparison with conventional balloon angioplasty, only the hydrogel balloon resulted in higher levels of thrombus dissolutio n (P < 0.05). In the intramural deposition studies, the efficiency of urokinase delivery was 0.0004% for systemic therapy, 0.004% for guidin g catheter infusion, 0.004% for Roubin catheter infusion, 0.08% for Di spatch catheter infusion, and 1.8% for hydrogel balloon delivery, The Dispatch catheter resulted in higher intramural drug levels than did a ll other techniques (P < 0.05), whereas the efficiency of urokinase de position was higher with the hydrogel balloon than with all other appr oaches (P < 0.05), In the porcine model, it is subsequently concluded that local delivery of urokinase by catheter-based techniques can resu lt in more complete lysis of intraluminal thrombus by using similar or lower doses of drug than by using conventional urokinase infusion tec hniques, Mechanical deformation of thrombus, possibly to increase the surface area available for thrombolysis and to physically disrupt clot , may be an important component of the mechanism of site-specific thro mbolysis, particularly with the hydrogel balloon. Local delivery techn iques also deposit significant quantities of urokinase at balloon angi oplasty sites, creating an intramural reservoir of drug that may resul t in prolonged local thrombolysis. (C) 1997 Wiley-Liss, Inc.