Maintenance Dose of Warfarin in Sheep and Effect of Diet: A Preliminary Report

ABSTRACT

Sheep models are widely used to evaluate the feasibility of various cardiac assist devices. Anticoagulation therapy postoperatively, however, is seldomly reported on. Continuous heparin infusion is often used, but is cumbersome due to long-term line management with the risk of infection and dislodgement. We contemplated using warfarin instead and started a pilot dose-finding study. Three sheep were given oral warfarin between 0.1 and 0.3 mg/kg/day. Prothrombin time was monitored and INR was calculated daily. If the INR did not reach a target of 2.5–3.5, warfarin dose was doubled. We found that sheep required a dose of warfarin between 1.6 and 2.4 mg/kg/day to raise the INR to the target zone. In a subsequent study to evaluate the effect of diet on INR in sheep, three sheep were fed alfalfa hay or alfalfa pellets in a crossover design. All the animals were given warfarin at the dose of 1.6 mg/kg. The diet was switched when the INR reached the target zone of 2.5–3.5. Hay-fed animals reached the target INR on days 6 and 7. On the other hand, pellet-fed animals did not reach the target value by day 7 with the initial dose and required 2.4 mg/kg of warfarin to achieve the goal. Hay raised the INR faster and higher than pellets with the same warfarin dose. Hay may be advantageous when using oral warfarin therapy in sheep.

Keywords: :

• Sheep
• anticoagulation
• oral warfarin therapy
• alfalfa hay
• alfalfa pellet

ACKNOWLEDGMENTS

This study is funded by the American Heart Association National Scientist Development Grant 0635219N (to Olaf Reinhartz).