Investigation of a chronic single-stage sheep Fontan model

• DOI: 10.1016/j.xjon.2024.06.018
• Publication Date: 2024-07-04T17:03:19Z
• Authors: John M. Kelly; Zinan Hu; Felipe Takaesu; Tatsuya Watanabe; Judd Storrs; Benjamin Blais; Satoshi Yuhara; Adrienne Morrison; Kirsten Nelson; Anudari Ulziibayar; Eric Heuer; Cole Anderson; Michael Jimenez; Joseph Leland; Raphael Malbrue; Carmen Arsuaga-Zo...; Laurie Goodchild; Aymen Naguib; Christopher McKee; Jordan Varner; Cameron DeShetler; Joshua Spiess; Andrew Harrison; Brian Boe; Aimee K. Armstrong; Arash Salavitabar; Kan Hor; Rajesh Krishnamurthy; Andrew R. Yates; Toshiharu Shinoka; Sergio A. Carrillo; Michael E. Davis; Alison L. Marsden; Christopher K. Br...

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.