Intermittent hypoxia (IH) is a condition characterized by repeated episodes of reduced oxygen availability interspersed with periods of normal oxygen levels, commonly associated with high-altitude exposure, obstructive sleep apnea, and certain training regimens (1). The recurrent nature of IH poses a significant challenge to the cardiovascular system, particularly in terms of autonomic regulation which plays a crucial role in maintaining cardiovascular homeostasis (2).

Cardiovascular autonomic regulation, primarily assessed through heart rate variability (HRV) and blood pressure variability (BPV), reflects the balance between sympathetic and parasympathetic influences on the heart and vasculature (3). HRV and BPV are well-established non-invasive methods for evaluating autonomic nervous system activity, with alterations in these indices serving as markers of increased cardiovascular risk (4,5).

Exposure to IH has been shown to induce sympathoexcitation and impair parasympathetic activity, potentially leading to cardiovascular dysfunction over time (6). Animal studies have demonstrated that IH can cause sustained elevation of blood pressure and structural alterations within the autonomic nervous system (7). However, the effects of IH on cardiovascular autonomic regulation in healthy adults remain incompletely understood, particularly in terms of acute versus chronic responses.

Recent research has highlighted that IH can result in reduced HRV and increased BPV, suggesting heightened sympathetic activity and decreased vagal modulation (8,9). Such alterations have been linked to various cardiovascular pathologies, including hypertension, myocardial infarction, and arrhythmias (10). Understanding the acute impact of IH on cardiovascular autonomic regulation is essential for developing preventive and therapeutic strategies aimed at mitigating potential adverse effects.

The present study aims to investigate the effects of acute IH exposure on cardiovascular autonomic regulation in healthy adults by analyzing HRV and BPV parameters. It is hypothesized that IH will result in reduced HRV and increased BPV, indicating an imbalance in autonomic regulation favoring sympathetic dominance.

Study Design and Participants:

This study was designed as a randomized crossover trial conducted on 30 healthy adults (15 males and 15 females), aged between 20 and 30 years (mean age: 25 ± 3 years). All participants were non-smokers, without any history of cardiovascular, respiratory, or metabolic disorders. Written informed consent was obtained from all participants.

Experimental Protocol:

The participants were exposed to two experimental conditions on separate days with at least a 48-hour washout period between sessions to avoid carry-over effects:

1. Normoxia (Control Condition): Participants breathed room air (FiO2: 21%) continuously for 60 minutes.
2. Intermittent Hypoxia (IH Condition): Participants were exposed to repeated cycles of hypoxia (FiO2: 12%) for 5 minutes, followed by 5 minutes of normoxia, repeated over a total period of 60 minutes.

The experimental sessions were conducted in a temperature-controlled room, and participants were instructed to abstain from caffeine, alcohol, and heavy exercise for at least 24 hours prior to each session.

Cardiovascular Autonomic Measurements:

Cardiovascular autonomic regulation was assessed using heart rate variability (HRV) and blood pressure variability (BPV).

• Heart Rate Variability (HRV): Electrocardiogram (ECG) signals were recorded using a portable ECG monitoring device for the entire duration of the sessions. HRV analysis was performed using time-domain indices such as SDNN (Standard Deviation of NN intervals) and RMSSD (Root Mean Square of Successive Differences), along with frequency-domain indices such as LF (Low Frequency), HF (High Frequency), and LF/HF ratio.
• Blood Pressure Variability (BPV): Continuous blood pressure monitoring was carried out using a non-invasive arterial tonometry device. BPV parameters, including systolic BPV and diastolic BPV, were derived from the recorded signals.

Data Analysis:

Data were segmented into baseline (last 10 minutes of normoxia condition) and experimental phase (last 10 minutes of intermittent hypoxia condition). HRV and BPV parameters were computed using specialized software designed for signal analysis.

Statistical analysis was performed using paired t-tests to compare the cardiovascular parameters between the normoxia and intermittent hypoxia conditions. A p-value of <0.05 was considered statistically significant.

A total of 30 participants (15 males, 15 females) completed the study without any adverse events. The results are presented below in Tables 1 and 2, which summarize the HRV and BPV parameters under both Normoxia and Intermittent Hypoxia (IH) conditions.

Heart Rate Variability (HRV):

Exposure to IH resulted in significant alterations in HRV parameters compared to the normoxia condition. The SDNN and RMSSD values were significantly reduced during IH, indicating reduced overall HRV and parasympathetic activity. Additionally, the LF/HF ratio was significantly increased, suggesting a shift towards sympathetic dominance (Table 1).

Table 1: Heart Rate Variability (HRV) Parameters under Normoxia and Intermittent Hypoxia Conditions

As shown in Table 1, the SDNN and RMSSD values decreased significantly, while the LF/HF ratio increased significantly during IH exposure compared to the normoxia condition.

Blood Pressure Variability (BPV):

Intermittent hypoxia also had a notable impact on blood pressure variability. There was a significant increase in systolic and diastolic BPV, indicating elevated vascular reactivity during the IH condition (Table 2).

Table 2: Blood Pressure Variability (BPV) Parameters under Normoxia and Intermittent Hypoxia Conditions

According to Table 2, all BPV parameters were significantly higher during the IH condition compared to the normoxia condition.

The findings suggest that acute intermittent hypoxia adversely affects cardiovascular autonomic regulation by reducing HRV and increasing BPV, indicating enhanced sympathetic activity and vascular reactivity.

The present study aimed to investigate the impact of acute intermittent hypoxia (IH) on cardiovascular autonomic regulation in healthy adults by assessing heart rate variability (HRV) and blood pressure variability (BPV). The findings demonstrate that IH significantly reduces HRV and increases BPV, indicating enhanced sympathetic activity and diminished parasympathetic modulation.

Reduced HRV during IH, as reflected by significant decreases in SDNN and RMSSD, suggests impaired autonomic control characterized by reduced vagal tone and increased sympathetic dominance (1). These findings are consistent with previous studies reporting decreased HRV following exposure to IH in both experimental and clinical settings (2,3). The increased LF/HF ratio observed in this study further supports the notion of heightened sympathetic activation during IH (4).

Previous studies have indicated that IH-induced autonomic dysfunction is primarily mediated through alterations in the central nervous system, particularly the activation of chemoreceptors and alterations in baroreceptor sensitivity (5,6). Animal studies have demonstrated that IH can cause structural and functional changes within the central and peripheral nervous systems, leading to sustained sympathoexcitation (7). Additionally, studies have suggested that the hypoxia-induced elevation of oxidative stress and inflammatory markers may contribute to autonomic dysfunction (8,9).

The increase in BPV observed during IH in this study suggests enhanced vascular reactivity, potentially reflecting heightened sympathetic vasomotor tone (10). This finding aligns with previous research indicating that IH can elevate blood pressure variability due to increased peripheral resistance and altered baroreflex sensitivity (11). Chronic exposure to IH has been associated with hypertension and cardiovascular remodeling, highlighting the potential clinical implications of such autonomic alterations (12,13).

While the acute effects of IH on HRV and BPV are evident, the mechanisms underlying these changes remain incompletely understood. Studies suggest that intermittent hypoxia-induced oxidative stress, inflammation, and endothelial dysfunction may play critical roles in autonomic dysregulation (14). Moreover, genetic predisposition and individual susceptibility to hypoxia may influence the magnitude of autonomic changes observed during IH (15).

The findings of this study have important implications for understanding the cardiovascular risks associated with recurrent hypoxic exposure. Individuals exposed to IH conditions, such as those with obstructive sleep apnea or high-altitude dwellers, may be at increased risk of developing autonomic dysfunction and related cardiovascular disorders (16,17). Additionally, athletes who employ hypoxic training for performance enhancement should be aware of potential adverse effects on cardiovascular regulation (18).

Nevertheless, this study has some limitations. The findings are based on acute exposure to IH, and therefore, the effects of chronic exposure remain unclear. Furthermore, the study population consisted of healthy adults, which may limit the generalizability of the findings to individuals with underlying cardiovascular conditions. Future research should focus on the long-term effects of IH on autonomic function and explore potential interventions aimed at mitigating these adverse effects.

In conclusion, this study demonstrates that acute intermittent hypoxia significantly alters cardiovascular autonomic regulation by reducing HRV and increasing BPV. These findings suggest that IH may predispose individuals to cardiovascular dysfunction through heightened sympathetic activity and decreased parasympathetic control. Further research is warranted to elucidate the mechanisms underlying these changes and to explore potential preventive strategies.

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