JTCVS Open (Oct 2024)
Investigation of a chronic single-stage sheep Fontan modelCentral MessagePerspective
- John M. Kelly, MD,
- Zinan Hu, BS,
- Felipe Takaesu, BS,
- Tatsuya Watanabe, MD, PhD,
- Judd Storrs, PhD,
- Benjamin Blais, MD,
- Satoshi Yuhara, MD,
- Adrienne Morrison, BA,
- Kirsten Nelson, BA,
- Anudari Ulziibayar, MD,
- Eric Heuer, BA,
- Cole Anderson, BS,
- Michael Jimenez, BA,
- Joseph Leland, BA,
- Raphael Malbrue, DVM,
- Carmen Arsuaga-Zorrilla, DVM, MS,
- Laurie Goodchild, DVM,
- Aymen Naguib, MD,
- Christopher McKee, MD,
- Jordan Varner, BA,
- Cameron DeShetler, BS,
- Joshua Spiess, BA,
- Andrew Harrison, BA,
- Brian Boe, MD,
- Aimee K. Armstrong, MD,
- Arash Salavitabar, MD,
- Kan Hor, MD,
- Rajesh Krishnamurthy, MD,
- Andrew R. Yates, MD,
- Toshiharu Shinoka, MD, PhD,
- Sergio A. Carrillo, MD,
- Michael E. Davis, PhD,
- Alison L. Marsden, PhD,
- Christopher K. Breuer, MD
Affiliations
- John M. Kelly, MD
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio; The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio; Address for reprints: John M. Kelly, MD, Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, 700 Children’s Dr, Columbus, OH 43214.
- Zinan Hu, BS
- Department of Mechanical Engineering, Stanford University, Stanford, Calif; Department of Pediatrics, Stanford University, Stanford, Calif; Department of Bioengineering, Stanford University, Stanford, Calif
- Felipe Takaesu, BS
- Biochemistry, Cell, and Developmental Biology Graduate Training Program, Laney Graduate School, Emory University, Atlanta, Ga; Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, Ga
- Tatsuya Watanabe, MD, PhD
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Judd Storrs, PhD
- Department of Radiology, Nationwide Children’s Hospital, Columbus, Ohio
- Benjamin Blais, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Satoshi Yuhara, MD
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Adrienne Morrison, BA
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Kirsten Nelson, BA
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Anudari Ulziibayar, MD
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Eric Heuer, BA
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Cole Anderson, BS
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Michael Jimenez, BA
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Joseph Leland, BA
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Raphael Malbrue, DVM
- Center for Comparative Medicine, University of Virginia, Charlottesville, Va
- Carmen Arsuaga-Zorrilla, DVM, MS
- Animal Resources Core, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Laurie Goodchild, DVM
- Animal Resources Core, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Aymen Naguib, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Christopher McKee, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Jordan Varner, BA
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Cameron DeShetler, BS
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Joshua Spiess, BA
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- Andrew Harrison, BA
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio
- Brian Boe, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Aimee K. Armstrong, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Arash Salavitabar, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Kan Hor, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Rajesh Krishnamurthy, MD
- Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio; Department of Radiology, Nationwide Children’s Hospital, Columbus, Ohio
- Andrew R. Yates, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Toshiharu Shinoka, MD, PhD
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio; The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Sergio A. Carrillo, MD
- The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Michael E. Davis, PhD
- Biochemistry, Cell, and Developmental Biology Graduate Training Program, Laney Graduate School, Emory University, Atlanta, Ga; Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, Ga; Children’s Heart Research and Outcomes Center, Children’s Healthcare of Atlanta and Emory University, Atlanta, Ga
- Alison L. Marsden, PhD
- Department of Mechanical Engineering, Stanford University, Stanford, Calif; Department of Pediatrics, Stanford University, Stanford, Calif; Department of Bioengineering, Stanford University, Stanford, Calif
- Christopher K. Breuer, MD
- Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio; The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio
- Journal volume & issue
-
Vol. 21
pp. 268 – 278
Abstract
Objectives: Our goal was to conduct a hemodynamic analysis of a novel animal model of Fontan physiology. Poor late-term outcomes in Fontan patients are believed to arise from Fontan-induced hemodynamics, but the mechanisms remain poorly understood. Recent advances in surgical experimentation have resulted in the development of a chronic sheep model of Fontan physiology; however, detailed analysis of this model is lacking. Methods: We created a single-stage Fontan model in juvenile sheep with normal biventricular circulation. The superior vena cava was anastomosed to the main pulmonary artery, and the inferior vena cava was connected to the main pulmonary artery using an expanded polytetrafluoroethylene conduit. Longitudinal hemodynamics, including catheterization and magnetic resonance imaging were evaluated. Results: Four out of 12 animals survived, with the longest surviving animal living 3 years after single-stage Fontan. We showed a significant era effect regarding survival (1 out of 8 and subsequently 3 out of 4 animals surviving beyond 2 months) attributed in large part to the procedural learning curve. Key characteristics of Fontan hemodynamics, namely systemic venous hypertension and low normal cardiac output, were observed. However, recapitulation of passive human Fontan hemodynamics is affected by volume loading of the right ventricle given an anatomic difference in sheep azygous venous anatomy draining to the coronary sinus. Conclusions: A significant learning curve exists to ensure long-term survival and future surgical modifications, including banding of the main pulmonary artery and ligation of the azygous to coronary sinus connection are promising strategies to improve the fidelity of model hemodynamics.
