A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis.

To explore brain involvement in chronic fatigue syndrome (CFS), the statistical parametric mapping of brain MR images has been extended to voxel-based regressions against clinical scores. Using SPM5 we performed voxel-based morphometry (VBM) and analysed T(1) - and T(2) -weighted spin-echo MR signal levels in 25 CFS subjects and 25 normal controls (NC). Clinical scores included CFS fatigue duration, a score based on the 10 most common CFS symptoms, the Bell score, the hospital anxiety and depression scale (HADS) anxiety and depression, and hemodynamic parameters from 24-h blood pressure monitoring. We also performed group × hemodynamic score interaction regressions to detect locations where MR regressions were opposite for CFS and NC, thereby indicating abnormality in the CFS group. In the midbrain, white matter volume was observed to decrease with increasing fatigue duration. For T(1) -weighted MR and white matter volume, group × hemodynamic score interactions were detected in the brainstem [strongest in midbrain grey matter (GM)], deep prefrontal white matter (WM), the caudal basal pons and hypothalamus. A strong correlation in CFS between brainstem GM volume and pulse pressure suggested impaired cerebrovascular autoregulation. It can be argued that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system (ANS).

Exercise-induced hypoxemia: fact or fallacy?

UNLABELLED: Whereas the prevalence of exercise-induced hypoxemia (EIH) in endurance athletes is commonly reported as approximately 50%, most previous studies have not corrected PaO2 for exercise-induced hyperthermia. Furthermore, although a detrimental effect on aerobic performance has been assumed, no study has measured arterial oxygen content (CaO2) in this context. PURPOSE: To determine the effect of temperature-correcting PaO2 values for rectal, arterial blood, esophageal, and exercising muscle temperatures during exercise on CaO2 and the prevalence of EIH. METHODS: Twenty-three trained males (age 26 +/- 5 yr; VO2peak 65.2 +/- 1.6 mL x kg-1 x min-1) performed incremental treadmill exercise to exhaustion with PaO2 corrected for simultaneous temperature measurements at all four sites. EIH was defined as DeltaPaO2 >or= 10 mm Hg. RESULTS: : With no temperature correction, DeltaPaO2 was -20.8 +/- 5.0 mm Hg and prevalence was 96% (n = 23), but when corrected for rectal temperature, DeltaPaO2 was -14.7 +/- 7.8 mm Hg and prevalence was 73% (n = 20); for arterial blood temperature, DeltaPaO2 was -7.7 +/- 6.5 mm Hg and prevalence was 35% (n = 20); and for esophageal temperature, DeltaPaO2 was -8.1 +/- 7.7 mm Hg and prevalence was 48% (n = 23), although when corrected for active muscle temperature, DeltaPaO2 was +8.2 +/- 7.8 mm Hg and prevalence was 0% (n = 10). There were no significant changes in CaO2 except for uncorrected values, and there was no correlation between DeltaPaO2 and VO2peak. CONCLUSIONS: Although the prevalence of EIH depends on the temperature correction applied to PaO2 values, in no case is there a significant change in CaO2 or any relationship with maximal aerobic power.

Plasma lactate accumulation is reduced during incremental exercise in untrained women compared with untrained men.

The lactate threshold (LT) is commonly reported as not different between sexes, yet lower blood lactate concentrations have been reported in women during submaximal exercise. The purpose of the present study was to measure the changes in plasma lactate concentration [La(-1)] in men and women during incremental cycle ergometer exercise using the same protocol and compare the data using several different methods of analysis. A group of untrained men (n = 21) and women (n = 22) were studied and venous blood drawn at regular intervals during and after exercise for assay of plasma [La(-1)]. Plasma [La(-1)] increased during exercise in both sexes, reaching higher values in men, both at exhaustion (men 8.6 +/- 2.3 mmol l(-1); women 6.2 +/- 2.3 mmol l(-1); P = 0.01) and post-exercise (men 11.8 +/- 2.1 mmol l(-1); women 10.2 +/- 2.4 mmol l(-1); P = 0.03). Logarithmic transformation of the data yielded LT values that were not different between sexes (men 44.2 +/- 12.9; women 50.2 +/- 12.6; %VO2peak; P = 0.45), yet both the 2 and 4 mmol l(-1) fixed concentration LT occurred at lower relative intensities in men (2 mmol l(-1): men 50.9 +/- 12.9; women 66.9 +/- 11.1; %VO2peak; P = 0.01). 4 mmol l(-1): men 75.7 +/- 11.0; women 90.6 +/- 9.2; VO2peak; P = 0.01). However, when the plasma [La(-1)] was examined in both sexes throughout exercise, using a single exponential function, plasma [La(-1)] was significantly lower in women (P < 0.05) at all relative intensities between 30 and 100%VO2peak. While the basis of this sex difference is unknown, reduced plasma [La(-1)] during submaximal exercise in women may offset to some degree the endurance performance disadvantage of their lower VO2peak.

Time and sample site dependency of the optimized co-rebreathing method.

PURPOSE: A new method to estimate hemoglobin mass (Hbmass) requires capillary blood and rebreathing a carbon-monoxide (CO) bolus for 2 min. We hypothesized that incomplete circulatory mixing of CO could confound this method, so we compared capillary with venous blood to determine whether sampling site altered the percentage of carboxyhemoglobin (%HbCO) and the reliability and accuracy of the "2-min Hbmass." The conventional 20-min CO-rebreathing procedure was used as the Hbmass criterion. METHODS: In the first experiment (N=12), both fingertip capillary and antecubital venous blood were sampled 4 and 6 min after commencing 2 min of CO-rebreathing. Within 8 d, these subjects completed two 2-min and one 20-min CO-rebreathing periods. For the latter, capillary and venous blood were collected simultaneously after two 10-min periods of rebreathing. In a second experiment (N=6), both capillary and venous blood were sampled 4, 6, 8, 10, and 12 min after commencing 2 min of CO-rebreathing. A third experiment (N=6) evaluated the reliability of a modified 2-min CO-rebreathing test with capillary blood sampled at minutes 8 and 10. RESULTS: Typical error (TE) for the first two 2-min tests was 1.1% (90% confidence limits 0.9-1.8%), but the average Hbmass from 2-min capillary blood was 4.8% lower than from venous blood for the 20-min procedure. In the second experiment, peak venous %HbCO occurred at minute 6, and the difference between capillary and venous values was minimal (mean+/-SD; 0.08+/-0.07, 0.01+/-0.09) at minutes 8 and 10. TE for the third experiment was 1.2% (0.8-2.5%). CONCLUSION: A modified 2-min CO-rebreathing procedure using capillary or venous blood sampled 8 and 10 min after starting CO-rebreathing allows complete circulatory mixing and provides an accurate and reliable estimate of Hbmass.

Effect of a synthetic progestin on the exercise status of sedentary young women.

CONTEXT: The impact of progestins on exercise performance in women has not been previously studied. OBJECTIVE: The objective of this study was to examine the effect of a synthetic progestin on aspects of exercise status in young women. DESIGN, PATIENTS, SETTING: Twenty-three young, healthy, habitually sedentary women participated in a single-blind, randomized, counterbalanced, cross-over study in a university-based laboratory setting. INTERVENTION: Two monophasic oral contraceptive pills (OCPs) were administered in which the dose of the synthetic progestin, norethisterone, was 2-fold different but the dose of the synthetic estrogen, ethinyl estradiol, was constant. During each month of OCP aspects of exercise status were assessed during incremental exercise to exhaustion and steady-state submaximal exercise and with a performance test. MAIN OUTCOME MEASURES: The main outcome measures were peak oxygen uptake (VO(2peak)), respiratory exchange ratio (RER), time to exhaustion, lactate concentrations, and total work done. RESULTS: Peak heart rates were approximately 95% of age-predicted values with both OCP preparations, whereas VO(2peak) was approximately 30% above age-predicted values. Peak postincremental exercise plasma lactate concentrations exceeded those reported for males and females, whereas the RER was below expected values throughout both incremental and steady-state exercise. The effects on VO(2peak) and RER were increased with the higher dose progestin OCP, as were exercise time to exhaustion and total work done. CONCLUSION: Synthetic progestins in OCP formulations can have a significant effect on the exercise status of young, sedentary women, possibly through an effect on stroke volume and a shift in the principal energy substrate used during exercise from carbohydrate to lipid.

Rectal temperature correction overestimates the frequency of exercise-induced hypoxemia.

INTRODUCTION: Exercise-induced hypoxemia (EIH) occurs in an uncertain proportion of endurance trained athletes. Whereas blood gas measurements must be corrected for core temperature at the time of sampling, the commonly used rectal temperature readings may not be the most appropriate. METHODS: Ten males [mean peak oxygen uptake, (.-)VO(2peak), 65.4 +/- 7.0 mL x kg x min] performed incremental treadmill exercise from rest to exhaustion with radial artery blood samples collected at the end of each 2-min workload for gas analysis. The thermogenic effect of exercise was monitored with rectal, arterial blood, and esophageal temperature probes, and the values obtained at all three sites, simultaneous with blood sampling, were used to correct the standard blood gas measurements made at 37 +/- C. RESULTS: The mean increase in rectal temperature across exercise (1.4 +/- 0.4 +/- C) was approximately half that recorded in radial arterial blood (2.3 +/- 0.5+/- C) and the esophagus (2.4 +/- 0.5 degrees C). In consequence, the uncorrected fall in PaO2 across exercise of 15.4 +/- 8.2 mm Hg was reduced to 8.4 +/- 7.7 mm Hg when corrected for rectal temperature, and to 2.9 +/- 7.4 and 2.1 +/- 8.8 mm Hg when corrected for arterial blood and esophageal temperatures. Using a fall of > or = 10 mm Hg as the index of EIH, the proportion in the 10 subjects in the present study fell from 80% (uncorrected) through 50% (rectal correction) to 20% (arterial blood and esophageal corrections). CONCLUSION: When correcting arterial blood gas values for the thermogenic effects of exercise, the proportion of athletes meeting the definition of EIH depends on the site of core temperature measurement.

Impact of menstrual cycle phase on the exercise status of young, sedentary women.

The purpose of the present study was to compare exercise status during the follicular (FP) and luteal (LP) phases of the menstrual cycle of a single group of young, sedentary women, where the marked differential in the blood concentrations of 17beta-oestradiol ([E(2)]) and progesterone ([P(4)]) has the potential to alter the metabolic response to exercise. Fourteen females [21.8 (4.0) years, peak oxygen uptake ( VO(2peak)) <45 ml x kg (-1) x min(-1)] performed both incremental exercise to exhaustion and steady-state submaximal cycle ergometer exercise while measurements were made of several metabolic and hormonal variables. With the incremental exercise test, time to exhaustion, maximal power output and total work done were not different between the two phases, nor were the absolute values for VO(2peak) or the corresponding values for ventilation ( VE), respiratory frequency ( f(R)) and heart rate (HR). Resting, end-exercise and peak (post-exercise) plasma lactate concentrations and the lactate threshold were not different between the two phases either. However, as the workloads increased during the incremental protocol, plasma lactate concentration, carbon dioxide output ( VCO(2)) and the respiratory exchange ratio (RER) all were lower during LP, while oxygen uptake ( VO(2)) was higher. With steady-state submaximal exercise, at workloads corresponding to 25% and 75% of menstrual cycle phase-specific VO(2peak), VO(2) and the oxygen pulse ( VO(2)/HR) were higher and RER and plasma lactate concentration lower during LP. Regardless of phase, [E(2)] increased with both incremental and steady-state submaximal exercise, while [P(4)] was unchanged. It is concluded that while exercise capacity, as defined by VO(2peak) and the lactate threshold, is unaffected by cycle phase in young, sedentary women, the metabolic responses in the LP during both incremental and steady-state submaximal exercise suggest a greater dependence on fat as an energy source.

Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome.

PURPOSE: Previous studies in chronic fatigue syndrome (CFS) have reported reductions in maximal oxygen uptake (VO(2max)), yet often the testing procedures have not followed accepted guidelines, and gender data have been pooled. The present study was undertaken to reevaluate exercise capacity in CFS patients by using "gold standard" maximal exercise testing methodology and stratifying results on a gender basis. METHODS: Sixteen male and 17 female CFS patients and their gender-, age-, and mass-matched sedentary controls performed incremental exercise to volitional exhaustion on a stationary cycle ergometer while selected cardiorespiratory and metabolic variables were measured. RESULTS: VO(2max) in male CFS patients was not different from control values (CFS: 40.5 +/- 6.7; controls: 43.3 +/- 8.6; mL x kg(-1) x min(-1)) and was 96.3 +/- 17.9% of the age-predicted value, indicating no functional aerobic impairment (3.7 +/- 17.9%). In female CFS patients, VO(2max) was lower than control values (CFS: 30.0 +/- 4.7; controls: 34.2 +/- 5.6; mL x kg(-1) x min(-1), P = 0.002), but controls were higher than the age-predicted value (112.6 +/- 15.4%, P = 0.008) whereas the CFS patients were 101.2 +/- 20.4%, indicating no functional aerobic impairment (-1.2 +/- 20.4%). Maximal heart rate (HR(max)) in male CFS patients was lower than their matched controls (CFS: 184 +/- 10; controls: 192 +/- 12; beats x min(-1); P = 0.016) but was 99.1 +/- 5.5% of their age-predicted value. In female CFS patients, HR(max) was not different from controls (CFS: 183 +/- 11; controls: 186 +/- 10; beats x min(-1)) and was 98.9 +/- 5.1% of the age-predicted value. The VO(2) at the lactate threshold (LT) in each gender group, whether expressed in mL x kg(-1) x min(-1) or as a percentage of VO(2max), was not different between CFS patients and controls. CONCLUSIONS: In contrast to most previous reports, the present study found that VO(2max), HR(max), and the LT in CFS patients of both genders were not different from the values expected in healthy sedentary individuals of a similar age.