Treatment of single functional ventricle is indisputably a significant healthcare challenge. It is the leading cause of death from any birth defect in the first year of life. Those who are fortunate to survive face lifelong disability for which there is no direct therapy, constituting an emerging public health concern. Currently, repair is performed in a complex series of 3 staged operations which are notorious for instability and mortality. This is attributable to the use of a systemic arterial shunt to provide a substantive source of pulmonary blood flow in the neonate. The endpoint of repair is a univentricular Fontan circulation, in which the vena cavae are connected to the pulmonary artery. Because there is no right-sided ventricular power source, venous return is profoundly altered and filling of the single ventricle is suboptimal. We have theorized that a means to modestly augment existing Fontan cavopulmonary flow (6-8 mmHg) would address these problems by reproducing more stable two-ventricle physiology and permitting stabilization and/or compression of surgical stages. Gradual reduction in support would permit adaptation to the higher pressure needed (10-15 mmHg) for a systemic venous source to independently perfuse the lungs. The functional parameters for a blood pump to provide low- pressure support in the complex 4-way flow anatomy of a cavopulmonary connection are markedly dissimilar to any other circulatory assist application: No such pump currently exists. We hypothesize that an actuator disk pump, based on the von Karman viscous pump, is optimal to provide cavopulmonary assist. With only one impeller, a catheter-based expandable rotary disk provides the preferred low-pressure, high-volume flow in 4 opposing directions without risk of venous pathway obstruction. To develop this breakthrough innovation, our specific aims are to: 1) characterize the upstream, local, and downstream flow patterns induced by rotation of a central stabilizing body (actuator disk) within a 3-way """"""""T"""""""" and 4-way """"""""t"""""""" cavopulmonary connection, 2) define the optimal geometric and surface characteristics of a bi-conical expandable rotary impeller to augment cavopulmonary flow using advanced numerical modeling and flow visualization, 3) optimize the hemodynamic, biocompatibility, and thrombogenicity performance of a rotary disk pump through in vitro feedback from mock flow loop, flow visualization, and hemolysis studies, 4) demonstrate percutaneous viscous pump support in an animal model of univentricular Fontan circulation. We will accomplish these aims by intersecting expertise in: computational fluid dynamic modeling;surface streamlining;flow visualization;in vitro modeling;physiologic control;thrombogenicity;elastomer chemistry;nitinol metallurgy;microcoil fabrication;catheter disposables;rotary blood pump design;prototyping;and clinically rooted in vivo studies. At completion, an easily implemented percutaneous technology which dramatically improves Fontan circulatory status will be delivered as a predicate device to clinical use. In patients with univentricular Fontan circulations - young and old - this safe, simple, and reliable method to augment cavopulmonary flow will address their unresolved health needs.

Public Health Relevance

We will develop a blood pump designed to provide cavopulmonary assist in a univentricular Fontan circulation. This will dramatically improve the healthcare of children and adults born with single ventricle heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL098353-03
Application #
8259153
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Kaltman, Jonathan R
Project Start
2010-08-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$498,077
Indirect Cost
$46,127
Name
Indiana University-Purdue University at Indianapolis
Department
Surgery
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Delorme, Yann T; Rodefeld, Mark D; Frankel, Steven H (2017) Multiblock High Order Large Eddy Simulation of Powered Fontan Hemodynamics: Towards Computational Surgery. Comput Fluids 143:16-31
Delorme, Yann T; Kerlo, Anna-Elodie M; Anupindi, Kameswararao et al. (2014) Dynamic Mode Decomposition of Fontan Hemodynamics in an Idealized Total Cavopulmonary Connection. Fluid Dyn Res 46:041425
Iliff, Bp; Kerlo, Aem; Chen, J et al. (2014) In Vitro Ultrasound Measurements of Powered and Unpowered Total Cavopulmonary Connection. Austin J Biomed Eng 1:
Giridharan, Guruprasad A; Ising, Mickey; Sobieski, Michael A et al. (2014) Cavopulmonary assist for the failing Fontan circulation: impact of ventricular function on mechanical support strategy. ASAIO J 60:707-15
Pal, Abhro; Anupindi, Kameswararao; Delorme, Yann et al. (2014) Large eddy simulation of transitional flow in an idealized stenotic blood vessel: evaluation of subgrid scale models. J Biomech Eng 136:
Anupindi, Kameswararao; Lai, Weichen; Frankel, Steven (2014) Characterization of oscillatory instability in lid driven cavity flows using lattice Boltzmann method. Comput Fluids 92:7-21
Shetty, Dinesh A; Frankel, Steven H (2013) Assessment of stretched vortex subgrid-scale models for LES of incompressible inhomogeneous turbulent flow. Int J Numer Methods Fluids 73:
Giridharan, Guruprasad A; Koenig, Steven C; Kennington, Jeffrey et al. (2013) Performance evaluation of a pediatric viscous impeller pump for Fontan cavopulmonary assist. J Thorac Cardiovasc Surg 145:249-57
Delorme, Yann T; Anupindi, Kameswararao; Frankel, Steven H (2013) Large Eddy Simulation of FDA's Idealized Medical Device. Cardiovasc Eng Technol 4:
Anupindi, Kameswararao; Delorme, Yann; Shetty, Dinesh A et al. (2013) A novel multiblock immersed boundary method for large eddy simulation of complex arterial hemodynamics. J Comput Phys 254:

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