Background Conventional ECMO is cumbersome and is associated with high morbidity and mortality. We are developing the Paracorporeal Ambulatory Assist Lung (PAAL), designed to ambulate lung failure patients during bridge to transplant or recovery. In this study, we investigated the in-vitro and acute in-vivo performance of the PAAL. Methods The PAAL features a 1.75 inch diameter cylindrical HFM bundle of stacked sheets, with a surface area of 0.65 m2 integrated with a centrifugal pump. The PAAL was tested on the bench for hydrodynamic performance, gas exchange and hemolysis. The PAAL was then tested in 40–60 kg adult sheep (n=4) for 6h. The animals were cannulated with an Avalon Elite 27 Fr. DLC inserted through the right external jugular into the SVC, RA and IVC. Results The PAAL pumped over 250 mmHg at 3.5 L/min at a rotation speed of 2100 RPM. Oxygenation performance met the target of 180 ml/min at 3.5 L/min of blood flow in vitro, resulting in a gas exchange efficiency of 278 ml/min/m2. The normalized index of hemolysis (NIH) for the PAAL and cannula was 0.054 g/100L (n=2) at 3.5 L/min, as compared to 0.020 g/100L (n=2) for control (DLC cannula and a Centrimag pump). Plasma-free hemoglobin (pfHb) was below 20 mg/dL for all animals. Blood left the device 100% oxygenated in vivo and oxygenation reached 181 ml/min at 3.8 L/min. Conclusions The PAAL met in vitro and acute in vivo performance targets. 5 day chronic sheep studies are planned in the near term.
Mechanical ventilation and ECMO are the only viable treatment options for lung failure patients at the end stage, including ARDS and COPD. These treatments however are associated with high morbidity and mortality due to long wait times for lung transplant. Contemporary clinical literature has shown ambulation improves post-transplant outcomes in lung failure patients. Given this, we are developing the PAAL, a truly wearable artificial lung that allows for ambulation. In this study, we targeted 180 ml/min oxygenation and determined the form factor for a hollow fiber membrane (HFM) bundle for the PAAL. Based on a previously published mass transfer correlation we modeled oxygenation efficiency as a function of fiber bundle diameter. Three benchmark fiber bundles were fabricated to validate the model through in-vitro blood gas exchange at blood flow rates from 1 to 4 L/min according to ASTM standards. We used the model to determine a final design, which was characterized in-vitro through a gas exchange as well as a hemolysis study at 3.5 L/min The percent difference between model predictions and experiment for the benchmark bundles ranged from 3% to 17.5% at the flowrates tested. Using the model, we predicted a 1.75 inch diameter bundle with 0.65 m2 surface area would produce 180 ml/min at 3.5 L/min blood flow rate. The oxygenation efficiency was 278 ml/min/m2 and the Normalized Index of Hemolysis (NIH) was less than 0.05g/100L. Future work involves integrating this bundle into the PAAL for which an experimental prototype is under development in our laboratory.
Recent studies show improved outcomes in ambulated lung failure patients. Ambulation still remains a challenge in these patients. This necessitates development of more compact and less cumbersome respiratory support specifically designed to be wearable. The Paracorporeal Ambulatory Assist Lung (PAAL) is being designed for providing ambulatory support in lung failure patients during bridge to transplant or recovery. We previously published in vitro and acute in vivo results of the PAAL. This study further evaluates the PAAL for 5 days. Five-day in vivo studies with the PAAL were conducted in 50-60 kg sheep after heparinization (activated clotting time range: 190-250 s) and cannulation with a 27 Fr. Avalon Elite dual-lumen cannula. The animals were able to move freely in a stanchion while device flow, resistance, and hemodynamics were recorded hourly. Oxygenation and hemolysis were measured daily. Platelet activation, blood chemistry, and comprehensive blood counts are reported for preoperatively, on POD 0, and POD 5. Three animals survived for 5 days. No study termination resulted from device failure. One animal was terminated on POD 0 and one animal was terminated at POD 3. The device was operated between 1.93 and 2.15 L/min. Blood left the device 100% oxygenated. Plasma-free hemoglobin ranged 10.8-14.5 mg/dl. CD62-P expression was under 10%. Minimal thrombus was seen in devices at explant. Chronic use of the PAAL in awake sheep is promising based on our study. There were no device-related complications over the study course. This study represents the next step in our pathway to eventual clinical translation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.