Nao Umei1,2,3,4, Angela Lai5, Jennifer Miller5, Suji Shin5, Kalliope Roberts5, Saif Ai Qatarneh5, Shingo Ichiba6,7,8, Atsuhiro Sakamoto6,7,8, Keith E Cook5. 1. Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. u-nao@nms.ac.jp. 2. Department of Anesthesiology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. u-nao@nms.ac.jp. 3. Department of Surgical Intensive Care Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. u-nao@nms.ac.jp. 4. Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA. u-nao@nms.ac.jp. 5. Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA. 6. Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. 7. Department of Anesthesiology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. 8. Department of Surgical Intensive Care Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
Abstract
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator. METHODS: The circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance. RESULTS: During ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group. CONCLUSIONS: This model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator. METHODS: The circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance. RESULTS: During ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group. CONCLUSIONS: This model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.
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