End stage lung disease (ESLD) is associated with a high mortality in infants and children. We are currently funded by NIH grant 2R01 HD015434-29 to develop a pediatric artificial lung (PAL) which would provide a successful path toward recovery or transplantation in pediatric patients with ESLD. Over the past 4 years we have accomplished the following as a result of this grant: 1) designed a low resistance, high efficiency artificial gas exchange device (MLung) which can be configured in any size for infants and children; 2) characterized optimal pulmonary artery-to-left atrial cannulation for lung implantation in small (~20-30 kg) sheep; 3) evaluated the effects of the PAL on cardiopulmonary physiology in normal sheep; 4) developed a reproducible model of ESLD in small sheep and by the end of year 5 will have a similar model in infant sheep; 5) provided initial data demonstrating remediation of adverse physiology in our lung disease sheep model using the Novalung and heparin anticoagulation; and 6) created the software and processes to automate CO2 removal. Our laboratory has also demonstrated the ability of circuit nitric oxide (NO) and argatroban coating to prevent extracorporeal device associated thrombosis and to decrease the risk of transcutaneous infection. Based on all of this work, we now have the disease model, the artificial lung, the cannulation strategy, the gas exchange automation processes, and the means for local anticoagulation to ready the PAL for clinical trial by achieving the following specific aims:
Specific Aim 1 : To evaluate MLung gas exchange, resistance, thrombogenicity, and durability.
Specific Aim 2 : To provide a successful approach for local anticoagulation for the PAL using NO/argatroban coating and NO in the PAL sweep flow.
Specific Aim 3 : To prepare for clinical application by automating CO2 control; using oxygen enrichment devices to provide MLung sweep flow; and testing long-term reliability and effectiveness of the PAL system in our model of pediatric ESLD.
Specific Aim 4 : To bring together a team to plan the PAL clinical trial.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Tamburro, Robert F
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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