Stable Cytokine Network during Hypoxia and Exercise in Patients with Fontan Circulation

Abstract

Background Patients with Fontan circulation are often advised to avoid hypoxic exposure due to presumed cardiopulmonary vulnerability. Low-grade inflammation has also been reported in this population and may be influenced by hypoxia and/or exercise. Based on the potential interaction between hypoxia and submaximal exercise in modulating inflammatory signaling, we hypothesized that this combination could exacerbate subclinical inflammation. Methods Eighteen clinically stable patients with Fontan circulation (age 25 ± 6 years, 9 female, NYHA I) underwent a submaximal cycling step test under normoxia, followed by 24 hours of normobaric hypoxia (FiO₂ ≈ 15 %, ∼2500 m), and a second test under hypoxia at the :envihab research facility of the German Aerospace Centre. Venous blood was sampled at rest and peak exercise to analyse cytokines (IL-2, IL-6, TNF-α, TNF-β), adipo-myokines (irisin, asprosin), and immune cell indices (WBC, lymphocytes, neutrophils, NLR, PLR, SII). Results Baseline cytokine levels and cell counts were within reference ranges. Exercise induced a mild increase in WBC under both conditions without affecting derived indices (p ≤ 0.05). Cytokine concentrations remained stable. Irisin increased after normoxic (p ≤ 0.05) but not hypoxic exercise; asprosin showed no significant changes. Conclusion Moderate normobaric hypoxia combined with submaximal exercise did not elicit systemic immune activation in stable patients with Fontan circulation. These data challenge assumptions of latent immune vulnerability and support the safety of controlled hypoxic exposure in the tested cohort.