Over the last 25 years our laboratory research on extracorporeal gas exchange and perfusion (ECMO) has progressed from oxygenator design, through the physiologic response to ECMO, through the development of extracorporeal technology to safe, simple automated systems which can be used to support cardiac or pulmonary function for days. Clinical success with ECMO indicates that expansion to total mechanical extracorporeal life support (ECLS) is feasible, but expansion of the technology requires a solution to two problems: 1) anticoagulation and thrombocytopenia, and 2) multiple organ failure. Despite many innovative approaches to anticoagulation and new prosthetic surfaces, systemic heparin anticoagulation is still required for extracorporeal circulation. A new group of anticoagulants inhibit clotting at specific early stages of the cascade. We will evaluate inhibitors of Factor IXa and Xa, used systemically or on the surface. Nitric oxide, a potent inhibitor of platelet adherence and activation, can be incorporated into the plastic materials and ventilating gas in the ECMO system, eliminating surface thrombogenesis, platelet consumption, and systemic anticoagulation without affecting endogenous platelet function. This research will develop and characterize thrombosis prevention leading to prolonged extracorporeal circulation without anticoagulation or thrombocytopenia. This will allow extension of mechanical life support from weeks to months, and initiate new approaches to ECLS. The non-thrombogenic surface combined with high blood flow and a unique albumin-based hemodiafiltration system can extend mechanical life support to liver failure and sepsis. The significance of this research is to decrease the mortality from cardiorespiratory and multiple organ failure. By studying prolonged support in experimental animals we will improve our understanding of the mechanisms and treatment of multiple organ failure.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015434-19
Application #
6181370
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Wright, Linda
Project Start
1980-08-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
19
Fiscal Year
2000
Total Cost
$380,310
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Surgery
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Sun, Liqun; Kaesler, Andreas; Fernando, Piyumindri et al. (2018) CO2 clearance by membrane lungs. Perfusion 33:249-253
Church, Joseph T; Alghanem, Fares; Deatrick, Kristopher B et al. (2017) Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation. ASAIO J 63:766-773
Alghanem, Fares; Bryner, Benjamin S; Jahangir, Emilia M et al. (2017) Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload. ASAIO J 63:223-228
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Wo, Yaqi; Li, Zi; Brisbois, Elizabeth J et al. (2015) Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S-Nitroso-N-acetyl-D-penicillamine. ACS Appl Mater Interfaces 7:22218-27
Brisbois, Elizabeth J; Davis, Ryan P; Jones, Anna M et al. (2015) Reduction in Thrombosis and Bacterial Adhesion with 7 Day Implantation of S-Nitroso-N-acetylpenicillamine (SNAP)-Doped Elast-eon E2As Catheters in Sheep. J Mater Chem B 3:1639-1645
Alghanem, Fares; Davis, Ryan P; Bryner, Benjamin S et al. (2015) The Implantable Pediatric Artificial Lung: Interim Report on the Development of an End-Stage Lung Failure Model. ASAIO J 61:453-8

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