Effect of time of 7E3 administration on rt-PA-induced reperfusion: study in a canine model of thrombus-based occlusion-reperfusion

Chimeric version of the murine monoclonal antibody, 7E3 has been proposed f or the early restoration of coronary artery patency during thrombolytic the rapy. We determined the optimal time for administration of 7E3 during recom binant tissue plasminogen activator (rt-PA)-induced thrombolysis using a ca nine model of coronary artery thrombosis. After 30 min of thrombotic occlus ion, microspheres were injected to assess regional myocardial blood flow, f ollowed by a 90-min rt-PA infusion. Dogs were randomized to three groups wh erein 7E3 (0.8 mg kg(-1), i.v.) war administered either 5 min before rt-PA (Group I), at the first evidence of thrombolysis (Group II). or after the c ompletion of rt-PA infusion (Group III). Hemodynamic parameters were monito red for 6 h after which infarct size was estimated. Time to occlusion/reper fusion was similar in all groups. In the rt-PA alone group. 78% arteries re occluded after 60 min of reperfusion. The incidence of reocclusion was lowe r in Groups II (25%, P = 0.04) and III (0%, P < 0.01). All arteries (100%) were patent at the end of the protocol in Group III vs 50% remaining patent in Group I (P = 0.01). Arterial patency was maintained longer in Group III (301 min, n = 10), compared with Groups I (124 min, n = 5) and II (124 min , n = 6). Arterial flow was greater in Group III (82%) compared with Groups I (27%) and II (35%) (P < 0.01). Regional myocardial blood flow and infarc t size were similar in all groups. The data indicate that the time of admin istration of 7E3 in conjunction viith rt-PA-induced thrombolysis influences patency status. The experimental results suggest that in the absence of as pirin and heparin, optimal thrombolysis is obtained when 7E3 is administere d after the completion of rt-PA infusion regimen. (C) 1999 Elsevier Science B.V. All rights reserved.