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 has been studied in a pig model.


METHODS
A total of 18 Göttingen minipigs were randomly divided into three treatment groups and subjected to cardiopulmonary bypass for 1 h. Heparin-treated animals received a bolus of unfractionated heparin of 400 IU/kg body weight. Recombinant hirudin was given by a bolus injection of 1 mg/kg body weight, followed by a 1 h lasting infusion of 1 mg/kg body weight per h. The heparin-anticoagulated animals and one group of the hirudin-treated animals additionally received aprotinin at a dosage of 17500 KIU/kg body weight (KIU, kallikrein inhibitory units). In the second group of r-hirudin-treated animals, the aprotinin was replaced by saline.


RESULTS
The extracorporeal circuit remained patent for a 1 h pump period in all of the animals studied. There was no evidence of vascular occlusion or clot formation 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 deposits were visible only in the heparin-treated animals and not in r-hirudin-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-treated animals compared with the r-hirudin/aprotinin-treated pigs. Studying 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/aprotinin-treated animals.


CONCLUSIONS
These data demonstrate that r-hirudin can be used successfully as an alternative anticoagulant to heparin during cardiac operations including cardiopulmonary bypass. The better preservation of platelet function suggests that r-hirudin may reduce the postoperative risk of bleeding.
Riess
F C
FC
Division of Thoracic and Cardiovascular Surgery, Kerckhoff-Klinik, Max-Planck-Institut für physiologische, Bad Nauheim, Germany.
Pötzsch
B
B
Behr
I
I
Jäger
K
K
Rössing
R
R
Bleese
N
N
Schaper
W
W
Müller-Berghaus
G
G
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001760:Bleeding Time; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005112:Extracorporeal Circulation; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology*; D010107:Oxygenators, Membrane; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine
D000925:Anticoagulants; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D006493:Heparin