Heparinless cardiopulmonary bypass with argatroban in dogs.
OBJECTIVE
Systemic heparinization is usually required for cardiopulmonary bypass (CPB). However, problems such as heparin-induced thrombocytopenia, protamine shock, and antithrombin III deficiency exist related to CPB with heparinization. The aim of this study was to evaluate argatroban (ARG) as a substitute for heparin during CPB.


METHODS
In the pilot study, blood samples were sequentially obtained from dogs with continuous infusion of ARG at a dose of 10 (n = 6), 20 (n = 6), or 30 (n = 6) microg/kg per min for 2 h without CPB. In the main study, dogs underwent CPB for 2 h with 10 (n = 6) or 30 (n = 6) microg/kg per min of ARG or with heparin with blood samples obtained sequentially. Thrombogenicity in each group was evaluated by observation of the blood-contacting surfaces of the CPB circuits with scanning electron microscopy (SEM). Evidence of thromboembolism in the dogs was also investigated in histological specimens of the kidney and spleen in addition to microscopic observation at autopsy.


RESULTS
In the pilot study, the activated coagulation time (ACT) reached a maximum level dose-dependently after continuous infusion of ARG for 30 min. ACT returned to the baseline value within 60 min after the termination of continuous infusion. In the main study, CPB with 30 microg/kg per min of ARG achieved thrombin-antithrombin III complex (TAT) level similar to that achieved by CPB with heparin. Platelet count with 30 microg/kg per min of ARG tended to be higher than that with heparin or 10 microg/kg per min of ARG. The SEM appearance of blood-contacting surfaces of the CPB circuits after infusion with 30 microg/kg per min of ARG appeared to be similar to that after infusion with heparin. Depositions on the blood-contacting surfaces of the CPB circuits were also frequently observed with 10 microg/kg per min of ARG.


CONCLUSIONS
Coagulability related to CPB was controlled by the appropriate ARG dosage without the use of heparin in dogs. ARG may be a substitute for heparin in CPB.
Rikitake
Kazuhisa
K
Department of Thoracic and Cardiovascular Surgery, Saga Medical School, 5-1-1 Nabeshima, Saga City, Saga 849-8501, Japan.
Okazaki
Yukio
Y
Naito
Kozo
K
Ohtsubo
Satoshi
S
Natsuaki
Masafumi
M
Itoh
Tsuyoshi
T
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000633:toxicity; D007430:Intraoperative Care / Q000379:methods*; D007668:Kidney / Q000098:blood supply; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D011183:Postoperative Complications / Q000517:prevention & control; D013449:Sulfonamides; D013927:Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban