RECOMBINANT HIRUDIN AS AN ANTICOAGULANT DURING CARDIAC OPERATIONS - EXPERIMENTS IN A PIG MODEL

Objective: The efficacy and safety of recombinant hirudin (r-hirudin) compared with heparin as an anticoagulant during open-heart surgery ha s been studied in a pig model. Methods: A total of 18 Gottingen minipi gs were randomly divided into three treatment groups and subjected to cardiopulmonary bypass for I h. Heparin-treated animals received a bol us of unfractionated heparin of 400 IU/kg body weight. Recombinant hir udin was given by a bolus injection of 1 mg/kg body weight, followed b y a 1 h lasting infusion of 1 mg/kg body weight per h. The heparin-ant icoagulated animals and one group of the hirudin-treated animals addit ionally received aprotinin at a dosage of 17 500 KIU/kg body weight (K IU, kallikrein inhibitory units). In the second group of r-hirudin-tre ated animals, the aprotinin was replaced by saline. Results: The extra corporeal circuit remained patent for a 1 h pump period in all of the animals studied. There was no evidence of vascular occlusion or clot f ormation in the r-hirudin-treated animals. The anticoagulant efficacy of the hirudin protocol used is further demonstrated by the results of electron-microscopical scans of the pump-line filters. Fibrin deposit s were visible only in the heparin-treated animals and not in r-hirudi n-treated pigs. Despite this strong anticoagulant effect, there was no evidence of an increased bleeding tendency in r-hirudin-treated pigs. Moreover, histological studies showed a statistically significant (P< 0.05) higher incidence of tissue bleeding in the heparin/aprotinin-tre ated animals compared with the r-hirudin/aprotinin-treated pigs, Study ing the platelet function, a statistically significant (P<0.01) better preserved ADP- and collagen-induced platelet aggregation was seen in the r-hirudin/aprotinin-treated animals when compared with heparin/apr otinin-treated animals. Conclusions: These data demonstrate that r-hir udin can be used successfully as an alternative anticoagulant to hepar in during cardiac operations including cardiopulmonary bypass. The bet ter preservation of platelet function suggests that r-hirudin may redu ce the postoperative risk of bleeding. (C) 1997 Elsevier Science B.V.