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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 |
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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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[1]Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients [J]. The Journal of heart and lung transplantation, 2013, 32(2): 141-156.
[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [J]. Circulation, 2013, 128: e240-e327.
[3]Molina EJ, Boyce SW. Current status of left ventricular assist device technology [J]. Seminars in Thoracic and Cardiovascular Surgery, 2013, 25(1): 56-63.
[4]Carpenter BA, Gonzalez CJ, Jessen SL, et al. A brief review of ventricular assist devices and a recommended protocol for pathology evaluations [J]. Cardiovascular Pathology, 2013, 22(5):408-415.
[5]McGee E, Katherine MS, Brown MC, et al. In vivo evaluation of the HeartWare MVAD Pump [J]. The Journal of Heart and Lung Transplantation, 2014, 33(4):366-371.[6]Zhang T, Wei X, Bianchi G, et al. A novel wearable pumplung device: in vitro and acute
in vivo study [J]. The Journal of Heart and Lung Transplantation, 2012, 31(1): 101-105.
[7]Schmitto JD, Burkhoff D, Avsar M, et al. Two axialflow Synergy MicroPumps as a biventricular assist device in an ovine animal model [J]. The Journal of Heart and Lung Transplantation, 2012,31(11): 1223-1229.
[8]Boni L, Sasaki T, Ferrier W T, et al. Challenges in longerterm mechanical support of fontan circulation in sheep [J]. ASAIO Journal, 2012, 58(1): 60-64.
[9]Connell JM, Khalapyan T, Almondhiry HA, et al. Anticoagulation of juvenile sheep and goats with heparin, warfarin, and clopidogrel [J]. ASAIO Journal, 2007, 53(2): 229-237.
[10]Saeed D, Fukamachi K. In vivo preclinical anticoagulation regimens after implantation of ventricular assist devices [J]. Artificial Organs, 2009, 33(7): 491-503.
[11]Sasaki T, Tsuda S, Trujillo M, et al. Maintenance dose of warfarin in sheep and effect of diet: a preliminary report [J]. Journal of Investigative Surgery, 2012, 25(1): 29-32.[12]刘修健, 吴广辉, 徐创业, 等. ChinaHeart 左心辅助装置的动物在体存活实验[J]. 中国生物医学工程学报, 2012, 31(5): 736-741.
[13]徐创业, 蔺嫦燕, 吴广辉, 等. ChinaHeart 心室辅助装置溶血性能研究[J]. 中国医疗设备 ISTIC, 2012, 27(11): 46-49.
[14]Slepian MJ, Chiu P, Sheriff J, et al. Device thrombogenicity emulation: A novel methodology to predict “Hot Spot” sites of thrombus formation in continuous flow VADs [J]. The Journal of Heart and Lung Transplantation, 2013, 32(4): S180.
[15]Eckman PM, John R. Bleeding and thrombosis in patients with continuousflow ventricular assist devices [J]. Circulation, 2012, 125(24): 3038-3047.
[16]Sun K, Son HS, Jung JS, et al. Korean artificial heart (AnyHeart): an experimental study and the first human application [J]. Artificial Organs, 2003, 27: 8-13.[17]Sato M, Harasaki H. Evaluation of platelet and coagulation function in different animal species using the xylum clot signature analyzer [J]. ASAIO Journal, 2002, 48:360-364.
[18]Boyce SW, Crevensten G, Fine RB. An anatomically compatible, wearless, reliable, and nonthrombogenic centrifugal blood pump [J]. The Annals of Thoracic Surgery, 2001, 71(3): S190.
[19]Kerkhoffs W, Schumacher O, Meyns B, et al. Design, development, and first in vivo results of an implantable ventricular assist device, MicroVad [J]. Artificial Organs, 2004, 28: 904-910.
[20]Tuzun E, Roberts K, Cohn WE, et al. In vivo evaluation of the HeartWare centrifugal ventricular assist device [J]. Texas Heart Institute Journal, 2007, 34(4): 406-411.
[21]Christiansen S, Perez A, Reul H, et al. In vivo experimental testing of a microaxial blood pump for right ventricular support [J]. Artificial Organs, 2006, 30(2): 94-100. |
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