Preclinical Study of Anticoagulation Regimens in Animals after Implantation of CHVAD
1 Beijing AnZhen Hospital, Capital Medical University, Beijing 100029, China
2 Beijing Institute of Heart Lung & Blood Vessel Diseases, Beijing 100029, China
3 China Heart Biomedical Inc, Suzhou 215123, China
Abstract Sheep models are often used to verify the blood compatibility, biological safety and reliability of VADs as well as the impact on physiological conditions of animals. Effective and safe anticoagulation regimens are strongly needed to reduce risks of thrombosis and bleeding. This study is to evaluate the effect of anticoagulation for animals after implantation of CHVAD with heparin and warfarin, aiming to offer anticoagulation data for longterm survival experiments and clinical applications. CHVAD models were established in six healthy sheep by constructing blood bypass of left ventricular →VAD →descending aorta. Heparin of 250 U/kg was injected through jugular vein during operation. Continuous heparin infusion was used in the prior four days after implantation to keep ACT and aPTT values as 15 to 20 times as the baseline. From the third day, proper dosage of warfarin was used orally to make INR in the target range of 12～20. Bleeding complications were closely monitored through the experiment. At the termination point, we examined whether there was thrombosis in the blood pump, grafts and anastomotic stoma. Macroscopical examinations were performed in major organs to check congestion and infarction. Tissues of the organs were collected to make HE staining to evaluate histopathological changes. Bleeding complications were not found in all animals throughout the experiments. Intraoperative ACT values were (326 ± 33) s. ACT values were（157±28）s in the prior four days, reaching the target range. The aPTT increased slowly and reached the lower limit of the target range at the fourth day. No thrombosis and fibrosis tissue were found in blood flow channel except for Sheep4. Pathological images showed no thrombosis, necrosis and microembolus in endstage organs under the anticoagulation regimen. Under the anticoagulation regimen of continuous intravenous heparin maintaining ACT 15～20 times the baseline and later oral warfarin maintaining INR values within the range of 12～20, thrombosis and bleeding complications could be well controlled in sheep models for CHVAD, providing reference for later animal experiments.
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