EVALUATION OF A LOW-MOLECULAR-WEIGHT HEPARIN AS AN ANTICOAGULANT IN A MODEL OF CARDIOPULMONARY BYPASS-SURGERY

Heparin, the classically used anticoagulant in cardiopulmonary bypass surgery, has several disadvantages such that alternate anticoagulants are being sought. Previous reports have described questionable safety with the clinical use of low molecular weight (LMW) heparin in cardiac surgery. The dog cardiopulmonary bypass model described herein may provide a useful means to study the pharmacology of new drugs prior to clinical use. Dogs were given a single loading dose of 250 USP units/kg (1.66 mg/kg) of unfractionated heparin (control) or 250 anti-factor Xa units/kg (2.3 mg/kg) LMW heparin and placed on bypass for 60 minutes. Prior to, during, and following bypass blood samples were taken to measure coagulation and hematological parameters. The dogs remained anesthetized for 150 minutes post-bypass. Post-operative blood loss and fibrin deposition in the arterial line filters were measured. Our findings showed there was no significant blood loss (heparin 452 +/- 67 gms; LMW heparin 289 +/- 82 gms) and no significant fibrin deposition (heparin 22 +/-3 gms; LMW heparin 28 +/- 7 gms) with the LMW heparin. These findings suggest that this LMW heparin should be safe and effective at the studied bolus dose as an anticoagulant for use in cardiopulmonary bypass surgery, and that protamine should be used to reverse the anticoagulant response after surgery.