Local delivery of antithrombin inhibits platelet deposition after balloon injury in a porcine coronary model

Background Thrombin activation and initiation of the coagulation process ca n lead to thrombotic complications after coronary angioplasty. A therapeuti c approach may be effectively to inhibit thrombin activity at the site of t he vessel wall injury. Objective The aim of the present study was to investigate the short-term ef fects of local delivery of antithrombin on coronary vessel wall injury in p igs. Methods A coronary balloon angioplasty was performed in the left anterior d escending artery. Twenty-four hours before the procedure, platelets were ma rked with Indium(111) and infused into the pig. Before catheterisation 100 U/kg of heparin was administered. Eight pigs received 250 U (5 ml) of antit hrombin and, as a control, eight received 10 mg of albumin (5 ml) delivered using a local drug delivery balloon catheter. Microscopic preparation of t he injured part of the vessel was performed, and the amount of radioactivit y was measured, giving the number of platelets per cm(2) Plasma antithrombi n level was measured before and after local delivery. The amount of antithr ombin in the vessel wall was measured using a semi-quantitative method invo lving anti-antithrombin antibodies. Results The number of platelets per cm(2) was significantly lower in the an tithrombin group (mean 2.3 x 10(6)) than in the control group (6.3 x 10(6), P = 0.02). No macroscopic thrombus was detected in the antithrombin group, whereas three out of eight pigs in the control group had visible thrombus formation (NS). There was an increase in the plasma concentration of antith rombin after local delivery. In the antithrombin group, antithrombin was de tected in the intima, the lumen part of the media and in the vasa vasorum. Conclusion Antithrombin can be administered and deposited locally in the co ronary vessel wall thereby reducing platelet deposition after balloon injur y. Coronary Artery Dis 9:823-829 (C) 1998 Lippincott Williams & Wilkins.