Current thoracic artificial lungs (TALs) have blood flow impedances greater than the natural lungs, which can result in abnormal pulmonary hemodynamics. This study investigated the impedance and gas transfer performance of a TAL with a compliant housing (cTAL). Fluid-structure interaction (FSI) analysis was performed using ADINA to examine the effect of the inlet and outlet expansion angle, θ, on device impedance and blood flow patterns. Based on the results, the θ=45° model was chosen for prototyping and in vitro testing. Glycerol was pumped through this cTAL at 2, 4, and 6 L/min at 80 and 100 beats/min, and the zeroth and first harmonic impedance moduli, Z0 and Z1, were calculated. Gas transfer testing was conducted at blood flow rates of 3, 5, and 7 L/min. FSI results indicated that the 45° model had an ideal combination of low impedance and even blood flow patterns, and was thus chosen for prototyping. In vitro, Z0=0.53 ± 0.06 mmHg/(L/min) and Z1=0.86 ± 0.08 mmHg/(L/min) at 4 L/min and 100 beats/min. Outlet PO2 and SO2 values were above 200 mmHg and 99.5%, respectively, at each flow rate. Thus, the cTAL had lower impedance than hard-shell TALs and excellent gas transfer.
The compliant Thoracic Artificial Lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL’s long term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anti-coagulant coatings was attached to sheep (n=5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was utilized. cTAL resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for non-device related issues. The cTAL’s resistance averaged 1.04±0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180±8 mL/min of oxygen with 3.18±0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis, but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0±0.1 g/dL thereafter. In a fourteen day experiment, the cTAL without anti-coagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged, except for device attachment related hemodilution. This suggests that patients treated with the cTAL shouldn’t require multiple blood transfusions. Once tested with anti-coagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.
The large, densely packed artificial surface area of artificial lungs results in rapid clotting and device failure. Surface generated nitric oxide (NO) can be used to reduce platelet activation and coagulation on gas exchange fibers, while not inducing patient bleeding due to its short half-life in blood. To generate NO, artificial lungs can be manufactured with PDMS hollow fibers embedded with copper nanoparticles (Cu NP) and supplied with an infusion of the NO donor S-nitroso-Nacetyl-penicillamine (SNAP). The SNAP reacts with Cu NP to generate NO. This study investigates clot formation and gas exchange performance of artificial lungs with either NOgenerating Cu-PDMS or standard polymethylpentene (PMP) fibers. One miniature artificial lung (MAL) made with 10 wt% Cu-PDMS hollow fibers and one PMP control MAL were attached to sheep in parallel in a veno-venous extracorporeal membrane oxygenation circuit (n = 8). Blood flow through each device was set at 300 mL/min, and each device received a SNAP infusion of 0.12 μmol/min. The ACT was between 110-180s in all cases. Blood flow resistance was calculated as a measure of clot formation on the fiber bundle. Gas exchange experiments comparing the two groups were conducted every 24 hours at blood flow rates of 300 and 600 mL/ min. Devices were removed once the resistance reached 3x baseline (failure) or following 72 hours. All devices were imaged using scanning electron microscopy (SEM) at the inlet, outlet, and middle of the fiber bundle. The Cu-PDMS NO generating MALs had a significantly smaller increase in resistance compared to the control devices. Resistance rose from 26 ± 8 and 23 ± 5 in the control and Cu-PDMS devices, respectively, to 35 ± 8 mmHg/(mL/min) and 72 ± 23 mmHg/(mL/min) at the end of each experiment. The resistance and SEM imaging of fiber surfaces demonstrate lower clot formation on Cu-PDMS fibers. Although not statistically significant,
The artificial lung has provided life‐saving support for pulmonary disease patients and recently afforded patients with severe cases of COVID‐19 better prognostic outcomes. While it addresses a critical medical need, reducing the risk of clotting inside the device remains challenging. Herein, a two‐step surface coating process of the lung circuit using Zwitterionic polysulfobetaine methacrylate is evaluated for its nonspecific protein antifouling activity. It is hypothesized that similarly applied coatings on materials integrated (IT) or nonintegrated (NIT) into the circuit will yield similar antifouling activity. The effects of human plasma preconditioned with nitric oxide‐loaded liposome on platelet (plt) fouling are also evaluated. Fibrinogen antifouling activities in coated fibers are similar in the IT and NIT groups. It however decreases in coated polycarbonate (PC) in the IT group. Also, plt antifouling activity in coated fibers is similar in the IT and NIT groups and is lower in coated PC and Tygon in the IT group compared to the NIT group. Coating process optimization in the IT lung circuit may help address difference in the coating appearance of outer and inner fiber bundle fibers, and the NO‐liposome significantly reduces (86%) plt fouling on fibers indicating its potential use for blood anticoagulation.
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