Imbalance in Cardiac Autonomic Nervous System Mediates Fatigue

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Aaron I. Vinik, M.D., Ph.D. Etta J. Vinik, MEd. Ying-Chuen Lai, M.D. Steven Morrison, Ph.D. Sheri R. Colberg, Ph.D. Serina Neumann, Ph.D. Joshua Edwards, MS. Scott Gerwe, M.D Carolina Casellini, M.D. Henri Parson, Ph.D.


Aims To explore the impact of the autonomic nervous system function in “disease-free” people for testing and appropriate therapies in different age-groups.

Methods Seventy-five disease-free volunteers who participated in a previous study were randomly selected from five age-groups (30-79 years) for a cross/sectional study to assess the impact of fatigue on cardiac/autonomic function by analysis of heart rate variability (HRV) and measures of cognitive and physical fatigue on quality-of-life-fatigue (QOLF) scores. Written informed consent was obtained and protocol approved. To induce fatigue, three 5-minute walking trials were performed on an instrumental treadmill, increasing the incline in increments of 2°/min to measure perceived exertion (RPE) at the beginning and end of each trial. Polar monitors measured heart rate (HR); a modified Borg 10-point scale measured RPE. Cardiac autonomic reflex tests (CART) with time/frequency domains analyzed HRV. QOLF scores were measured and analyzed for correlation with sympathetic/parasympathetic function on the Norfolk QOL-F fatigue scale.

Results QOL-F scores were not significantly different among 5 age groups, likely due to wide standard deviations and small subject numbers. Significant correlations between overall fatigue severity and several indices of HRV were found, independent of age, gender, and body mass index (p<0.05). Self-rated physical fatigue and compromised activities of daily living (ADLs) were related to sympathetic hyperactivity and autonomic imbalance (p=0.04). Participants in the (70–79-year-olds) category had impaired scores.

Conclusions The study identifies a relationship between autonomic nervous system function and cognitive and physical fatigue even in “disease-free” people in different age- groups and suggests that fatigue is impacted by somatic and autonomic nerve function. Higher self-ratings of perceived fatigue were associated with sympathovagal hyperactivity. Impaired HR response to exercise in older people corresponding with vagal over-activity, and paradoxically, best self-rated QOL-F, mandates clinical autonomic dysfunction testing and lifestyle therapies to prevent catastrophic events.

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VINIK, Aaron I. et al. Imbalance in Cardiac Autonomic Nervous System Mediates Fatigue. Medical Research Archives, [S.l.], v. 10, n. 2, feb. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 06 dec. 2022. doi:
Research Articles


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