Investigation of a chronic single-stage sheep Fontan model

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.

Keywords: Fontan; large animal model.

Graphical abstract

Creation of a chronic large animal model of Fontan palliation.

Figure 1

Overview of single-stage Fontan model and experimental approach. The single-stage Fontan model is created by anastomosing the superior vena cava to the pulmonary artery trunk in an end-to-side fashion (bidirectional Glenn) and by connecting the inferior vena cava to the pulmonary artery trunk with a synthetic expanded polytetrafluoroethylene graft (modified extracardiac Fontan). Detailed hemodynamic analysis demonstrates physiology that captures the salient features of Fontan physiology, namely systemic venous hypertension and decreased cardiac output. SVC, Superior vena cava; Ao, aorta; PA, pulmonary artery; LPA, left pulmonary artery; LA, left atrium; RA, right atrium; RV, right ventricle; LV, left ventricle; IVC, inferior vena cava; MRI, magnetic resonance imaging.

Figure 2

Single-stage fontan surgical model and hemodynamics. A, Intraoperative photo showing the Glenn (superior vena cava [SVC] to pulmonary artery [PA] connection) and Fontan (inferior vena cava [IVC] to PA connection with an expanded polytetrafluoroethylene graft). The right ventricle remains connected to the main PA to allow egress of coronary sinus flow. B, Significant and sustained elevation in systemic venous pressures. C, Decreased PA pulsatility. Pulse pressure is equal to the difference in systolic and diastolic pressures. D, Low normal cardiac index. Cardiac index is equal to the cardiac output normalized to body surface area. The sample was 9 preoperative, 4 <180 days postoperative, and 1 >180 days postoperative. Statistical significance determined with paired t test. ∗∗∗∗P < .0001.

Figure 3

Percent passive pulmonary blood flow to the lungs and change in venovenous collateral blood flow. A, Three-dimensional rendering of 4-dimensinal flow data from magnetic resonance imaging. The left azygos (LAz) vein (highlighted in red) is draining to the coronary sinus (CS). B, Example of a systemic venous to pulmonary venous collateral (highlighted in blue) between the right thoracic vein and the right upper pulmonary vein. C, Example of a systemic venous to systemic venous collateral between the thoracic intercostal veins via a left accessory azygous (LAAz) vein to the LAz vein, which anatomically drains to the CS. D, Percent “passive” flow defined as ([Glenn + Fontan]/total flow to the pulmonary arteries) × 100. E, Flow through the LAz vein as a percentage of cardiac output. F, Quantification of the blood flow bypassing the pulmonary circulation, termed right-to-left shunting, over time. G, Degree of systemic arterial desaturation from right to left shunting over time. Sample was 4 <180 days postoperative and 1 >180 days postoperative. Glenn, Superior vena cava to pulmonary artery connection; RV, right ventricle; Fontan, inferior vena cava to pulmonary arteyr connection; IVC, inferior vena cava; RUPV, right upper pulmonary vein; LV, left ventricle; LA, left atrium; RA, right atrium.