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: 6.06). 04/2010; 267(4):394-401. DOI: 10.1111/j.1365-2796.2009.02160.x
Source: PubMed


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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    • "This result is also not in contradiction to the abnormal proton handling that was reported during and after cessation of exercise in CFS patients [25,26]. "
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    ABSTRACT: The insufficient metabolic adaptation to exercise in Chronic Fatigue Syndrome (CFS) is still being debated and poorly understood. We analysed the cardiopulmonary exercise tests of CFS patients, idiopathic chronic fatigue (CFI) patients and healthy visitors. Continuous non-invasive measurement of the cardiac output by Nexfin(R) (BMEYE B.V. Amsterdam, the Netherlands) was added to the cardiopulmonary exercise tests. The peak oxygen extraction by muscle cells and the increase of cardiac output relative to the increase of oxygen uptake (DeltaQ'/DeltaV'O2) were measured, calculated from the cardiac output and the oxygen uptake during incremental exercise. The peak oxygen extraction by muscle cells was 10.83 +/- 2.80 ml/100ml in 178 CFS women, 11.62 +/- 2.90 ml/100ml in 172 CFI, and 13.45 +/- 2.72 ml/100ml in 11 healthy women (ANOVA: P=0.001), 13.66 +/- 3.31ml/100ml in 25 CFS men, 14.63 +/- 4.38 ml/100ml in 51 CFI, and 19.52 +/- 6.53 ml/100ml in 7 healthy men (ANOVA: P=0.008).The DeltaQ'/DeltaV'O2 was > 6 L/L (normal DeltaQ'/DeltaV'O2 [almost equal to] 5 L/L) in 70% of the patients and in 22% of the healthy group. Low oxygen uptake by muscle cells causes exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argues against deconditioning as a cause for physical impairment in these patients.
    Journal of Translational Medicine 01/2014; 12(1):20. DOI:10.1186/1479-5876-12-20 · 3.93 Impact Factor
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    • "We will use custom-built exercise apparatus to allow each participant to perform a standardised exercise protocol as previously described by members of our group [34,53,54], consisting of plantar flexion against fixed resistance during which time 31 P-MRS will be used to assess mitochondrial oxidative function (see Figure 2. In order to generate the 31P spectra, a 10 cm diameter 31P surface coil will be placed over the calf muscles, centred on the widest part of the gastrocnemius/soleus complex, for transmission and reception of the signal. "
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    ABSTRACT: Preterm infants represent up to 10% of births worldwide and have an increased risk of adverse metabolic outcomes in later life. Early life exposures are key factors in determining later health but current lifestyle factors such as diet and physical activity are also extremely important and provide an opportunity for targeted intervention.Methods/design: This current study, GROWMORE, is the fourth phase of the Newcastle Preterm Birth Growth Study (PTBGS), which was formed from two randomised controlled trials of nutrition in early life in preterm (24-34 weeks gestation) and low birthweight infants. 247 infants were recruited prior to hospital discharge. Infant follow-up included detailed measures of growth, nutritional intake, morbidities and body composition (Dual X Ray Absorptiometry, DXA) along with demographic data until 2 years corrected age. Developmental assessment was performed at 18 months corrected age, and cognitive assessment at 9-10 years of age. Growth, body composition (DXA), blood pressure and metabolic function (insulin resistance and lipid profile) were assessed at 9-13 years of age, and samples obtained for epigenetic analysis. In GROWMORE, we will follow up a representative cohort using established techniques and novel metabolic biomarkers and correlate these with current lifestyle factors including physical activity and dietary intake. We will assess auxology, body composition (BODPOD TM), insulin resistance, daily activity levels using ActigraphTM software and use 31P and 1H magnetic resonance spectroscopy to assess mitochondrial function and intra-hepatic lipid content. The Newcastle PTBGS is a unique cohort of children born preterm in the late 1990's. The major strengths are the high level of detail of early nutritional and growth exposures, and the comprehensive assessment over time. This study aims to examine the associations between early life exposures in preterm infants and metabolic outcomes in adolescence, which represents an area of major translational importance.
    BMC Pediatrics 12/2013; 13(1):213. DOI:10.1186/1471-2431-13-213 · 1.93 Impact Factor
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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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