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Changes in cardio-respiratory-vascular coupling dynamics across altitude gradients: a shift from linear synchrony to

Hongyun Liu^1,2, Shijing Wu^1,2, Ping Zhan^1,2

¹Medical Innovation Research Division, Chinese People's Liberation Army (PLA), General Hospital, Beijing, China.

Frontiers in Physiology

|May 11, 2026

Abstract

Introduction:

Prolonged high-altitude hypoxia induces acclimatization-related changes of multiple human physiological systems. The cardio-respiratory-vascular (CRV) coupling system, a core homeostasis-maintaining integrative mechanism, has incompletely elucidated altitude-acclimatization-related patterns. This study aimed to systematically explore CRV coupling and related physiological parameter changes across a broad altitude range in long-term acclimatized individuals.

Methods:

A multicenter cross-sectional study was conducted across five altitude gradients (HA0: <100 m, n=62; HA1: 1300 m, n=74; HA2: 3700 m, n=60; HA3: 4300 m, n=71; HA4: 5100 m, n=74). Synchronous electrocardiogram, hemodynamic, and respiratory signals were collected from healthy adults with ≥3 months of acclimatization. CRV coupling strength and complexity were computed, integrated with heart rate variability (HRV), hemodynamic, and respiratory parameters for analysis, with a HA4-specific physiological correlation network constructed.

Results:

CRV coupling strength showed altitude-dependent attenuation, while complexity increased with elevation. At HA4, HRV indices changed distinctly: Mean RR, logHF, and SampEn decreased (P<0.0001), and LF/HF increased (P<0.0001). SpO₂ declined and PPV rose with altitude; DBP (P = 0.0042) and MAP (P = 0.0204) increased only at HA4. Respiratory parameters exhibited asymmetric characteristics: AED and BR elevated (P<0.05), with BR_CV and EDC_CV increasing significantly only at HA4 (P<0.01). At HA4, coupling strength correlated positively with vagal activity/heart rate complexity and negatively with sympathetic dominance/respiratory variability, while complexity correlated positively with sympathetic dominance.

Discussion:

Long-term high-altitude acclimatization is characterized by a regulatory shift of the CRV system from strength-dominant linear synchrony to complexity-prioritized nonlinear flexibility. Extreme hypoxia may trigger enhanced nonlinear interactions to compensate for reduced linear synchrony, relying on respiratory rhythm stabilization and precise autonomic balance modulation. The findings may provide novel insights into the integrated physiology of high-altitude acclimatization.

Keywords:

altitude gradient autonomic regulation cardio-respiratory-vascular coupling hypoxic stress long-term high-altitude acclimatization

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