Abstract
Background: There has been an increasing demand of organs for lung transplant to save those who suffer from end-stage lung disease. However, the number of organ donations have never matched that of candidate recipients, leading to a high mortality rate on the waiting period for transplant. One potential approach to decrease the wait-list mortality is to develop an artificial gas-exchange device that can support lung function until the time of transplantation. We’ve started to develop a gas-exchange system that consists of silicone-based membrane lungs with methacryloyloxyethyl phosphorylcholine (MPC) polymer coating and tubing system for a longer-term use. Objective: The purpose of this study was to evaluate the long-term durability, oxygenation, and pressure loss of newly developed artificial lungs using a large animal model. Materials and methods: The surface area of the membrane lung is approximately 2 m2. Central ECMO from the pulmonary artery to the left atrium was introduced to a healthy female goat via left thoracotomy under general anesthesia (N=3). Unfractionated heparin infusion was utilized for anticoagulation (target activating clotting time: 150-200 sec). After recovery from the surgery, blood gas and flow pressure before and after the artificial lung with flow rates of 1, 2, and 3 L/min were tested weekly. Daily physiological data, regular blood biochemistry and coagulation tests, and histopathological findings after autopsy were also evaluated. Thrombus adhesion to the silicone membrane was evaluated using an electron microscopy after the experiments. Results: Durations for testing the artificial lungs were 53, 58, and 100 days. The experiments were terminated due to an accidental tubing event, a sudden cardiac complication, and massive renal hemorrhage. Averages of oxygen transfer rates (ml/min) and oxygen pressure gradients (mmHg) at each flow rate were 63.3 and 466.5 at 1 L/min, 118.3 and 291.3 at 2 L/min, and 152.7 and 138.2 at 3 L/min. Averages of flow pressures through the artificial lungs at each flow rate were 21.7 mmHg at 1 L/min, 44.7 at 2 L/min, and 66.9 at 3 L/min. No significant increase of pressure loss or decrease of oxygenation was observed throughout the experimental periods. Thrombus at the inlet of the membrane was mainly observed, but those inside and near the outlet were minor, indicating the long-term antithrombotic property of the polymer coating. Electron microscopical examinations revealed minimal thrombus formation on the hollow fiber membrane inside the lung. At autopsy, although micro-infarction and thrombus were observed in the heart and kidney, native lungs were well maintained without appreciable congestion. Conclusion: The newly developed MPC polymer-coated silicone-based lungs could be used stably for more than 50 days. Improving the oxygenation in higher blood flow rates with reduced pressure loss is our ongoing subject to work on.
Published Version
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