Influence of Simulated Altitude Exposure (2500 m) on Patients with Fontan Palliation Based on Circulating Hypoxia-Associated Factors

Abstract

Patients with a univentricular heart live with chronic hypoxia (75-85%) in their first years of life, which could affect adaptation to altitude or other hypoxic insults later in life. To test this hypothesis, we exposed 18 patients with Fontan circulation (age: 24.5 [16.3-38.8] years; f/m 9/9) to simulated altitude using normobaric hypoxia (15.2% oxygen, equivalent to 2500 masl) for 24 h. In blood samples obtained in normoxia (T1, 21% oxygen) and after 24 h hypoxia after a submaximal stress test, we measured hypoxia-regulated molecules involved in angiogenesis and tissue homeostasis. A significant increase was displayed for IL-10 (p = 0.001), CCL2 (p = 0.006), ANG-1 (p = 0.001), ANG-2 (p = 0.029), FGF-1 (p = 0.001) and FGF-2 (p = 0.024). E-Selectin (p < 0.001) and NRG-1 were significantly different at p = 0.026 at T2 compared to baseline. However, OPN and OSF-1 did not exhibit significant changes (p = 0.348; p = 0.065). Fontan patients show hypoxia-related protein patterns similar to healthy individuals despite intermittent hypoxemia, but their response to standardised hypoxia was described here for the first time, requiring further study.