Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome

Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
Journal of Internal Medicine (Impact Factor: 5.79). 04/2010; 267(4):394-401. DOI: 10.1111/j.1365-2796.2009.02160.x
Source: PubMed

ABSTRACT To examine muscle acid handling following exercise in chronic fatigue syndrome (CFS/ME) and the relationship with autonomic dysfunction.
Observational study.
Regional fatigue service. SUBJECTS & INTERVENTIONS: Chronic fatigue syndrome (n = 16) and age and sex matched normal controls (n = 8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load maximum voluntary contraction. Heart rate variability was performed during 10 min supine rest using digital photophlethysmography as a measure of autonomic function.
Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately postexercise (CFS: 1.1 +/- 0.5 mmol L(-1) min(-1) vs. normal: 3.6 +/- 1.5 mmol L(-1) min(-1), P < 0.001) and maximally (CFS: 2.7 +/- 3.4 mmol L(-1) min(-1) vs. control: 3.8 +/- 1.6 mmol L(-1) min(-1), P < 0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6 +/- 36.1 s vs. normal: 3.8 +/- 5.2 s, P < 0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r(2) = 0.6; P < 0.01). In CFS patients, in contrast, this significant normal relationship was lost (r(2) = 0.003; P = ns). In normal individuals, the maximum proton efflux following exercise were closely correlated with total heart rate variability (r(2) = 0.7; P = 0.007) this relationship was lost in CFS/ME patients (r(2) < 0.001; P = ns).
Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.

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    • "Patients with chronic fatigue syndrome have been found to have altered autonomic functioning during a tilt-table test (Freeman and Komaroff, 1997). Patients with chronic fatigue syndrome also have deficiency in intramuscular pH recovery, which can also be explained by ANS abnormalities (Jones et al., 2010). Our findings are compatible with these results. "
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    ABSTRACT: Both personality traits and autonomic functioning show as gender differences, but their relationship is not well understood. Medically unexplained symptoms are related to personality features and can be assessed by autonomic measurement. The patterns are hypothesised to identify gender differences. We recruited 30 male and 30 female healthy volunteers. All participants completed the Tridimensional Personality Questionnaire (TPQ) and heart-rate variability (HRV) measurement. Correlation analysis was performed to identify the relationships between TPQ scores and HRV parameters. For the subjects as a whole, the subdimension harm avoidance 4 (HA4, fatigability and asthenia) was found to be negatively correlated with low-frequency (LF) power, high-frequency (HF) power and total power (TP) of HRV. Novelty seeking 1 (NS1, exploratory excitability) was found to be positively correlated with LF power and TP. Multiple linear regression analysis revealed that the interactions exploratory excitability x gender and fatigability x gender are predictors of LF and HF power, respectively. Our result supports the hypothesis that personality features such as exploratory excitability and fatigability are associated with autonomic functioning and that gender is a moderator in these relationships.
    03/2013; 209(3). DOI:10.1016/j.psychres.2013.01.031
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    • "However, hyperventilation also increases the concentration of oxygen in the blood, resulting in a vasoconstrictive effect, in turn reducing CBF at rest and which would prolong cerebral vascular constriction after autonomic challenge . The 31 P MRS measures the intracellular pH, where CFS patients showed higher pH (more alkaline) both at rest (Jones et al., 2010) and after a fixed recovery period (Jones et al., 2012). The pH in skeletal muscle Fig. 2. Shows (a) the schematic protocol for skeletal muscle exercise, and (b) a schematic pH response illustration during a plantar flexion cycle. "
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    ABSTRACT: Cerebral blood flow (CBF) is maintained despite changing systemic blood pressure through cerebral vascular control, with such tight regulation believed to be under local tissue control. Chronic fatigue syndrome (CFS) associates with a wide range of symptoms, including orthostatic intolerance, skeletal muscle pH abnormalities and cognitive impairment. CFS patients are known to have reduced CBF and orthostatic intolerance associates with abnormal vascular regulation, while skeletal muscle pH abnormalities associate with autonomic dysfunction. These findings point to autonomic dysfunction as the central feature of CFS, and cerebral vascular control being influenced by factors outside of the brain, a macroscopic force affecting the stability of regional regulation. We therefore explored whether there was a physiological link between cerebral vascular control and skeletal muscle pH management in CFS. Seventeen consecutive CFS patients fulfilling the Fukuda criteria were recruited from our local CFS clinical service. To probe the static scenario, CBF and skeletal muscle pH were measured at rest using MRI and 31P magnetic resonance spectroscopy (31P-MRS). To examine dynamic control, brain functional MRI was performed concurrently with Valsalva manoeuvre (VM), a standard autonomic function challenge, while 31P-MRS was performed during plantar flexion exercise. Significant inverse correlation was seen between CBF and skeletal muscle pH at rest (r = − 0.67, p < 0.01). Prolonged cerebral vascular constriction during the sympathetic phase of VM was associated with higher pH in skeletal muscle after plantar flexion exercise (r = 0.69, p < 0.008). In conclusion, cerebral vascular control is closely related to skeletal muscle pH both at rest and after dynamic stimulation in CFS.
    Clinical neuroimaging 01/2013; 2:168-73. DOI:10.1016/j.nicl.2012.12.006 · 2.53 Impact Factor
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    • "A number of CFS patients may present with a dysfunctional autonomic system which may be related to an increase in heart rate and a decrease in systolic blood pressure. Additionally, irregularities in pH and heart rate variability occur in CFS patients following exercise (Jones et al., 2009; Newton et al., 2007). SORL1 refers to the sortilin-related receptor. "
    An International Perspective on the Future of Research in Chronic Fatigue Syndrome, 02/2012; , ISBN: 978-953-51-0072-0
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