E2 ModerateModerate confidencePEM not requiredCross-SectionalPeer-reviewedReviewed
Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome.
Wyller, Vegard Bruun, Saul, J Philip, Walløe, Lars et al. · European journal of applied physiology · 2008 · DOI
Quick Summary
This study looked at how the bodies of adolescents with ME/CFS respond to physical stress, specifically when lying down while pressure is applied to the legs and while squeezing a hand grip. Researchers found that ME/CFS patients had higher heart rates and stress hormone levels even at rest, and their cardiovascular system overreacted to the leg pressure test but underreacted during the hand grip exercise compared to healthy teenagers.
Why It Matters
Orthostatic intolerance and cardiovascular symptoms are common in ME/CFS, and this study provides objective physiological evidence of dysregulated sympathetic nervous system function in adolescent patients. Understanding these cardiovascular mechanisms may help explain exercise intolerance and symptom exacerbation, potentially informing future treatments targeting autonomic dysfunction.
Observed Findings
- At rest, CFS patients had significantly higher plasma norepinephrine and epinephrine levels and elevated resting heart rate compared to controls.
- During orthostatic stress (LBNP), CFS patients showed exaggerated increases in heart rate, diastolic blood pressure, and mean blood pressure.
- During isometric handgrip exercise under orthostatic stress, CFS patients showed attenuated (blunted) increases in heart rate and blood pressure.
- CFS patients had elevated diastolic blood pressure and mean blood pressure at baseline.
Inferred Conclusions
- Adolescents with ME/CFS have increased sympathetic nervous system activity at rest, as evidenced by elevated resting catecholamines and heart rate.
- The exaggerated cardiovascular response to orthostatic stress but attenuated response during exercise suggests abnormal sympathetic regulation and possible autonomic imbalance.
- Sympatetic nervous system dysfunction may be causally related to ME/CFS pathophysiology.
Remaining Questions
- Does sympathetic dysfunction precede ME/CFS onset, or does it develop secondary to chronic illness?
- How do these cardiovascular responses change over time in individual patients, and do they correlate with symptom severity or recovery?
What This Study Does Not Prove
This study cannot prove that sympathetic dysfunction causes ME/CFS—only that an association exists. The small sample size (n=15) limits generalizability to all adolescents with ME/CFS. The cross-sectional design does not establish whether cardiovascular dysregulation precedes ME/CFS onset or develops as a consequence of illness.
Tags
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Blood Biomarker
Phenotype:Pediatric
Method Flag:PEM Not DefinedSmall SampleStrong PhenotypingWeak Case Definition
Metadata
- DOI
- 10.1007/s00421-007-0634-1
- PMID
- 18066580
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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