COMPARISON OF DESULFATOHIRUDIN (REVASC) AND HEPARIN AS ADJUNCTS TO THROMBOLYTIC THERAPY WITH RETEPLASE IN A CANINE MODEL OF CORONARY-THROMBOSIS

1 We compared the direct thrombin inhibitor, desulfatohirudin (REVASC) and the indirect thrombin inhibitor, heparin, as adjuncts to thrombol ytic therapy with reteplase in a canine model of coronary artery throm bosis. 2 Reteplase (BM 06.022) is a recombinant unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in ana esthetized open chest dogs was induced by electrical injury. Left circ umflex coronary artery blood flow was monitored for 210 min with an el ectromagnetic flow probe. Twenty eight dogs were randomized to receive i.v. heparin (120 iu kg(-1) bolus plus 80 iu kg(-1) per h) or i.v. hi rudin (2.0 mg kg(-1) bolus plus 2.0 mg kg(-1) per h) 10 min before thr ombolysis preceded by i.v. acetylsalicyclic acid (20 mg kg(-1)) 5 min prior to anticoagulation. Every dog received an i.v. double bolus inje ction of 0.14 + 0.14 u kg(-1) (= 0.24 + 0.24 mg kg(-1)) reteplase, 30 min apart, 1 h after thrombus formation. 3 At comparable reperfusion r ates (12 out of 12 vs. 15 out of 16 dogs), hirudin enhanced time to re perfusion (14.3 +/- 1.4 vs. 23.2 +/- 3.4 min; P < 0.05) and completely prevented reocclusion after reperfusion in contrast to heparin (0 out of 11 vs. 7 out of 11 dogs; P < 0.05). Coronary blood flow quality wa s improved by hirudin as shown by a higher maximum blood flow after re perfusion (130 +/- 14.3 vs. 83 +/- 9.3% of baseline; P < 0.05), a high er blood flow level at 20, 30, 40, and 50 min after onset of thromboly sis (P < 0.05) and a longer cumulative patency time (195 +/- 1.7 vs. 1 66 +/- 12 min; P < 0.05). Activated partial thromboplastin time and bu ccal mucosa bleeding time were prolonged (P < 0.05) by either anticoag ulant, but did not differ significantly between groups. 4 The direct t hrombin inhibitor, desulfatohirudin, enhanced thrombolysis, prevented reocclusion and increased blood flow as compared with the indirect thr ombin inhibitor, heparin, when investigated at one dose level each and used in conjunction with reteplase.