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

IF 3.2 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

International journal of cardiology Pub Date : 2025-09-06 DOI:10.1016/j.ijcard.2025.133861

Julian Alexander von Hasselbach , Boris Dragutinovic , Nicole Müller , Johannes Breuer , Jens Tank , Jens Jordan , Wilhelm Bloch , Marijke Grau

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引用次数: 0

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.

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丰坦循环患者缺氧和运动时稳定的细胞因子网络。

背景：Fontan循环患者通常被建议避免缺氧暴露，因为假定心肺易损。在这一人群中也有轻度炎症的报道，可能受缺氧和/或运动的影响。基于缺氧和亚极限运动在调节炎症信号方面的潜在相互作用，我们假设这种组合可能会加剧亚临床炎症。方法：18例临床稳定的Fontan循环患者（年龄25岁 ± 6 岁，9名女性，NYHA I）在常压下进行了次最大循环步试验，随后进行了24 h的常压缺氧（FiO₂ ≈ 15 %,~2500 m），并在德国航空航天中心：envihab研究设施进行了第二次缺氧试验。静息和运动高峰时采集静脉血，分析细胞因子（IL-2、IL-6、TNF-α、TNF-β）、脂肪-肌因子（鸢尾素、asprosin）和免疫细胞指数（白细胞、淋巴细胞、中性粒细胞、NLR、PLR、SII）。结果：基线细胞因子水平和细胞计数在参考范围内。在两种情况下，运动均诱导WBC轻度增加，但不影响衍生指标（p ≤ 0.05）。细胞因子浓度保持稳定。常氧运动后鸢尾素升高（p ≤ 0.05），低氧运动后无升高；Asprosin无明显变化。结论：中度常压缺氧联合亚极限运动对稳定的方坦循环患者无系统性免疫激活作用。这些数据挑战了潜在免疫脆弱性的假设，并支持在测试队列中控制低氧暴露的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International journal of cardiology 医学-心血管系统

CiteScore

6.80

自引率

5.70%

发文量

758

审稿时长

44 days

期刊介绍： The International Journal of Cardiology is devoted to cardiology in the broadest sense. Both basic research and clinical papers can be submitted. The journal serves the interest of both practicing clinicians and researchers. In addition to original papers, we are launching a range of new manuscript types, including Consensus and Position Papers, Systematic Reviews, Meta-analyses, and Short communications. Case reports are no longer acceptable. Controversial techniques, issues on health policy and social medicine are discussed and serve as useful tools for encouraging debate.