Abstract 4143742: A Tale of Two Surgeries: Single Stage Versus Two Staged Approach to Creating an Ovine Model of Fontan Palliation

Introduction: Children born with single ventricle heart disease must undergo Fontan palliation. The lack of chronic preclinical animal models has limited the study of the significant end-organ complications that reduce the quality and duration of life. Here, we explore surgical strategies to improve animal survival in a chronic model of Fontan palliation. Methods: Sheep were divided based on the surgical approach: single stage Fontan (SS) versus staged Fontan. Controls were age/sex matched to the surgical cohort. The SS surgery consists of the Glenn, direct anastomosis of the SVC to the main pulmonary artery (MPA), and the Fontan, IVC connection to the MPA using a Gore-Tex conduit. Stage palliation consists of two stages. During stage 1 (S1), the IVC is connected to the MPA. A year later, stage 2 (S2) Glenn surgery is completed. Early post-op hemodynamics were monitored for 2 weeks through daily blood gases, an implanted telemetry device, and chest tube output. Results: SS had 5/6 sheep survive. S1 had 8/9 sheep survive (7/9 sheep continued to S2). S2 had 3/7 sheep survive. The trend in heart rate was not significantly different across the groups. However, we note a trend of an increase in heart rate in all groups on post-operation day (POD) 3 (144.90±20.72 BPM), which normalized POD10 (118.63±23.84 BPM) (p=0.006). Similarly, lactate peaked on POD0 (3.37±2.53mmol/L) and normalized POD2 (0.59±0.20 mmol/L) (p=0.0003) with no significant difference across groups. Creatine increased (SS) 1.7-fold (p=0.016) and (S2) 1.4-fold (p=0.032) from PO to POD1 and normalized by POD14. There was no significant elevation in creatine in S1. The chest tube output was not significantly (p=0.270) different across SS (4827.83±435.71 mL (11.6 days)), S1 (3305.33±1086.18 mL (10.5 days)), and S2 (4056±1890.26 mL (7 days)). Conclusions: We have demonstrated a similar clinical course for both surgical approaches of our ovine model with animals alive 1 to 3-year(s) post-operation. Future studies will follow the single stage approach given the improved animal survival and reduced surgical complexity. The ovine surgical model will allow the study of Fontan associated end-organ complications and be a testbed for potential curative solutions.