This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitchel, J. F. Articles by McKay, R. G. Search for Related Content PubMed PubMed Citation Articles by Mitchel, J. F. Articles by McKay, R. G.

(Circulation. 1995;91:785-793.)
© 1995 American Heart Association, Inc.

Articles

Enhanced Intracoronary Thrombolysis With Urokinase Using a Novel, Local Drug Delivery System

In Vitro, In Vivo, and Clinical Studies

Joseph F. Mitchel, DO; Daniel B. Fram, MD; Donald F. Palme, II, PhD; Rosemary Foster, BSc; Jeffrey A. Hirst, MD; Michael A. Azrin, MD; Laurine M. Bow, PhD; Adel M. Eldin, MD; David D. Waters, MD; Raymond G. McKay, MD

From the Departments of Internal Medicine and Cardiology, Hartford Hospital, University of Connecticut, Hartford.

Correspondence to Raymond G. McKay, MD, Director, Cardiac Laboratory, Hartford Hospital, 80 Seymour St, Hartford, CT 06115.

Background Current pharmacological regimens for treating intracoronary thrombus in the cardiac catheterization laboratory generally involve the administration of thrombolytic agents that result in a systemic fibrinolytic state and/or require prolonged arterial drug infusion. The purpose of the present study was to assess a new technique for treating intracoronary thrombus consisting of the local infusion of limited quantities of urokinase with a novel drug delivery device.

Methods and Results The Dispatch coronary infusion catheter is a new local drug delivery system that allows for the prolonged infusion of therapeutic agents at an angioplasty site while distal coronary flow is maintained. Three experimental protocols were performed to determine the in vitro, in vivo, and clinical efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20% porcine plasma was measured. Twenty-three thrombi were weighed before and after no treatment (n=5), "systemic" urokinase administration (n=4), local infusion of 150 000 U urokinase with a standard end-hole catheter (n=4), local infusion of saline with the Dispatch catheter (n=5), and local infusion of 150 000 U urokinase with the Dispatch catheter (n=5). Second, 25 porcine coronary arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty and then treated with ¹²³I-labeled urokinase that was administered either by the Dispatch catheter (150 000 U; n=16), intravenous systemic bolus (1 000 000 U; n=3), guiding catheter infusion (500 000 U; n=3), or local end-hole catheter infusion (150 000 U; n=3). All vessels were subsequently harvested to quantify intramural deposition and subsequent washout of urokinase at the angioplasty site. Finally, 19 patients with angiographic evidence of intracoronary thrombus were treated with local urokinase infusion with the Dispatch catheter either before or after balloon angioplasty or directional atherectomy. In vitro studies demonstrated that infusion of urokinase with the Dispatch catheter decreased thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase administration (25%), end-hole catheter urokinase infusion (32%), or infusion of saline by the Dispatch catheter (32%) (P.005). In vivo studies demonstrated immediate deposition of 0.12% of the urokinase delivered by the Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with an end-hole catheter (P<.001). Urokinase deposited by the Dispatch catheter persisted intramurally for at least 5 hours. Patient studies demonstrated reduction of thrombus-containing stenoses and complete disappearance of intracoronary thrombus in all cases in which 150 000 U urokinase was locally infused over 30 minutes. There was no evidence of abrupt closure, distal embolization, or no reflow in any patient.

Conclusions Local urokinase delivery with the Dispatch catheter can result in rapid and complete intracoronary thrombolysis using substantially less drug than standard thrombolytic techniques. Intramural deposition of drug with this technique creates a local reservoir of urokinase that may provide prolonged thrombolytic activity at the infusion site.

Key Words: thrombus • urokinase • drug administration

This article has been cited by other articles:

				T. Cyrus, H. Zhang, J. S. Allen, T. A. Williams, G. Hu, S. D. Caruthers, S. A. Wickline, and G. M. Lanza Intramural Delivery of Rapamycin With {alpha}v{beta}3-Targeted Paramagnetic Nanoparticles Inhibits Stenosis After Balloon Injury Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 820 - 826. [Abstract] [Full Text] [PDF]

				K. Kanamasa, Y. Inoue, N. Otani, N. Naito, H. Morii, A. Ikeda, M. Taniguchi, N. Ishida, T. Hayashi, and K. Ishikawa tPA via Infusion Catheters Followed by Continuous IV Infusion for 3 Days Prevents Intimal Hyperplasia After Balloon Injury Angiology, December 1, 2001; 52(12): 819 - 825. [Abstract] [PDF]

				I. Fishbein, M. Chorny, S. Banai, A. Levitzki, H. D. Danenberg, J. Gao, X. Chen, E. Moerman, I. Gati, V. Goldwasser, et al. Formulation and Delivery Mode Affect Disposition and Activity of Tyrphostin-Loaded Nanoparticles in the Rat Carotid Model Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1434 - 1439. [Abstract] [Full Text] [PDF]

				D. S Ettenson and E. R Edelman Local drug delivery: an emerging approach in the treatment of restenosis Vascular Medicine, May 1, 2000; 5(2): 97 - 102. [Abstract] [PDF]

				K. G. Lehmann, J. J. Popma, J. A. Werner, A. J. Lansky, and R. L. Wilensky Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans J. Am. Coll. Cardiol., March 1, 2000; 35(3): 583 - 591. [Abstract] [Full Text] [PDF]

				A. Gershlick Endovascular manipulation to restrict restenosis Vascular Medicine, August 1, 1998; 3(3): 177 - 188. [Abstract] [PDF]

				L. J Feldman and G. Steg Optimal techniques for arterial gene transfer Cardiovasc Res, September 1, 1997; 35(3): 391 - 404. [Abstract] [Full Text] [PDF]

				E. Camenzind, W. H. Bakker, A. Reijs, I. M. van Geijlswijk, E. Boersma, M. J. B. Kutryk, E. P. Krenning, J. R. T. C. Roelandt, P. W. Serruys, and P. W. Serruys Site-Specific Intracoronary Heparin Delivery in Humans After Balloon Angioplasty : A Radioisotopic Assessment of Regional Pharmacokinetics Circulation, July 1, 1997; 96(1): 154 - 165. [Abstract] [Full Text]

				O. Tahlil, M. Brami, L. J Feldman, D. Branellec, and Ph.G. Steg The DispatchTM catheter as a delivery tool for arterial gene transfer Cardiovasc Res, January 1, 1997; 33(1): 181 - 187. [Abstract] [Full Text] [PDF]