72-Hour in vivo evaluation of nitric oxide generating artificial lung gas exchange fibers in sheep

Abstract

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,

Zwitterionic poly-carboxybetaine coating reduces artificial lung thrombosis in sheep and rabbits

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Extracorporeal membrane oxygenation combined with continuous renal replacement therapy for the treatment of severe burns: current status and challenges

“…Lai et al. showed that fibres that release nitrogen oxide may be used on gas exchangers to reduce platelet activation and thrombosis without causing bleeding, which provides new insight into anticoagulation improvement during ECMO [ 76 ].…”

Bioengineering Progress in Lung Assist Devices

“…Surface-generated nitric oxide (NO) is used to reduce the platelet activation and coagulation on fibers. Approach [140] using PDMS hollow fibers embedded with copper nanoparticles (Cu NP) infused into the NO donor S-nitroso-N-acetyl-penicillamine to reacts with Cu NP to generate NO has shown potential. Although a reduction in blood clotting is observed, it dampens the oxygen transfer by 13.3% compared to baseline.…”