LOCAL UROKINASE DELIVERY WITH THE CHANNEL BALLOON - DEVICE SAFETY, PHARMACOKINETICS OF INTRACORONARY DRUG-DELIVERY, AND EFFICACY OF THROMBOLYSIS

The Channel balloon is a new local drug-delivery catheter that has the dual capability of high-pressure lesion dilation and low-pressure dru g infusion, The purpose of this study was to assess the safety and eff icacy of this device in the local delivery of urokinase in the porcine model, Three in vivo protocols were performed in 57 anesthetized swin e to assess the safety of Channel balloon use in the coronary vasculat ure, the pharmacokinetics of local urokinase delivery, and the ability of the catheter to lyse intraluminal thrombus, First, safety studies were performed in 18 coronary vessels in 13 pigs to compare angiograph ic and histologic changes following use of the Channel balloon with co nventional balloon angioplasty, Second, intramural deposition of I-123 -labeled urokinase was measured in 24 coronary arteries in 20 pigs to assess the efficiency and technical determinants of urokinase delivery and the time course of intramural drug retention. Finally, an in vivo thrombus model was used in 24 pigs to compare the thrombolytic capaci ty of local urokinase delivery with the Channel balloon in comparison with conventional urokinase infusion techniques. All balloon inflation s and drug infusions with the Channel balloon were well tolerated in a il animals without adverse angiographic, hemodynamic, or electrical se quelae. Comparative histologic studies with the Channel balloon demons trated no additional vessel trauma beyond that seen with conventional balloon angioplasty, Between 0.09 and 0.35% of infused urokinase was i ntramurally deposited, with intracoronary persistence for at least 5 h , Drug infusion pressure did not significantly affect drug deposition, although larger amounts of urokinase were deposited with larger ballo on:artery ratios and higher urokinase concentrations. In comparison to conventional systemic and guiding catheter infusions, local delivery of urokinase with the Channel balloon resulted in higher levels of clo t dissolution, These studies have demonstrated safe intracoronary use of the Channel balloon in the porcine model. Local infusion of urokina se with this device results in significant: intramural drug deposition that persists for at least 5 h. in comparison with conventional throm bolytic techniques, local urokinase delivery with the Channel balloon may result in enhanced intravascular thrombolysis. (C) 1997 Wiley-Liss , Inc.