Background
Heparin is the standard anticoagulant used during Cardiopulmonary Bypass (CPB). However, there are problems with heparin, including immunogenicity and variability of effect, that make a search for an alternative desirable. We have reported that dabigatran anticoagulation provides adequate conditions for CPB in a rabbit model. We used a sheep model of CPB in this current study to assess the efficacy of dabigatran and its reversibility with idarucizumab.
Methods
Twelve sheep were subjected to 120 minutes of CPB after anticoagulation with either intravenous dabigatran or heparin (N=6 per group). In both groups, activated clotting time (ACT), rapid-TEG reaction time (R), and blood gases were monitored during and after CPB. Plasma dabigatran concentrations were measured during and after CPB. After CPB, two sections of each arterial filter were examined for thrombus using electron microscopy. Idarucizumab or protamine was administered after CPB to reverse anticoagulation, and the sheep were monitored for a subsequent 24 hours. Plasma concentrations of inflammatory and coagulation markers were assessed at baseline, after 120 minutes of CPB, and 6 hours after reversal administration.
Results
After 120 minutes of CPB, there was no visible thrombus or fibrin observed on the arterial line filters in either the dabigatran or heparin groups. Plasma dabigatran concentrations during CPB were below the target concentration (5 µg/mL), ranging from 1.7±0.4 µg/mL to 3.4±1.5 µg/mL. In both groups, R and ACT values increased during CPB and then returned to nearly baseline levels after administration of the reversal agents. Interleukin-6 concentrations were elevated in the heparin group compared to the dabigatran group. Five sheep survived 24 hours after idarucizumab administration. Four out of 6 sheep survived 24 hours after the administration of protamine.
Conclusions
This study demonstrates that dabigatran effectively provides anticoagulation in a sheep CPB model, and idarucizumab successfully reverses its effects.