Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome

Abstract:

PURPOSE: To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria.

RESULTS: Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads.

CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Comment in:

Exercise limits in chronic fatigue syndrome. [Am J Med. 1997]

Graded exercise testing and chronic fatigue syndrome. [Am J Med. 1997]

 

Source: Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, Boda WL, Tapp WN, Natelson BH. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. 1996 Jun;100(6):634-40. http://www.ncbi.nlm.nih.gov/pubmed/8678084

 

Reduced oxidative muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15).

CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14).

In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Comment in: Chronic fatigue syndrome and skeletal muscle mitochondrial function. [Muscle Nerve. 1997]

 

Source: McCully KK, Natelson BH, Iotti S, Sisto S, Leigh JS Jr. Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. 1996 May;19(5):621-5. http://www.ncbi.nlm.nih.gov/pubmed/8618560

 

Use of exercise for treatment of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a condition that results in moderate to severe disability, the primary feature of which is fatigue of unknown origin. There is a lot of interest in classifying, characterising and treating patients with CFS. Currently, the two major theories of a medical cause of CFS are viral infection and immune dysregulation.

Patients report critical reductions in levels of physical activity, and many experience ‘relapses’ of severe symptoms following even moderate levels of exertion. Despite this, most studies report CFS patients to have normal muscle strength and either normal or slightly reduced muscle endurance.

Histological and metabolic studies report mixed results: CFS patients have either no impairment or mild impairment of mitochondria and oxidative metabolism compared with sedentary controls.

Current treatments for CFS are symptom-based, with psychological, pharmacological and rehabilitation treatments providing some relief but no cure. Immunological and nutritional treatments have been tried but have not provided reproducible benefits. Exercise training programmes are thought to be beneficial (if ‘relapses’ can be avoided), although few controlled studies have been performed.

CFS is a long-lasting disorder that can slowly improve with time, but often does not. Further studies are needed to better understand the multiple factors that can cause chronic fatigue illness, as well as the effect that exercise training has on the symptoms of CFS.

 

Source: McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of chronic fatigue syndrome. Sports Med. 1996 Jan;21(1):35-48. http://www.ncbi.nlm.nih.gov/pubmed/8771284

 

Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data

Comment on: Exercise responses and psychiatric disorder in chronic fatigue syndrome. [BMJ. 1995]

 

EDITOR,-In their study of exercise responses and psychiatric disorder in the chronic fatigue syndrome Russell J M Lane and colleagues claim to have detected abnormal lactate responses to subanaerobic threshold exercise in 31 of 96 patients. As no data are offered to support this statement, however, objective assessment of the validity of their findings is difficult.

The authors’ definition of an abnormal response is “lactate concentrations exceeding the upper 99% reference limit for normal control subjects at two or more time points.” However, only three samples were taken (before, immediately after, and 30 minutes after exercise), and a raised lactate concentration in the sample obtained before exercise began cannot be described as an abnormal response to exercise. Neither the method used to measure lactate nor its precision is given; assessment of the importance of the “abnormal” lactate concentrations could not be guessed at without this information, even if the authors had given details of the patients’ concentrations.

You can read the full comment along with the authors’ reply here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551191/pdf/bmj00618-0070a.pdf

 

Source: Hutchison AS. Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data. BMJ. 1995 Nov 11;311(7015):1304. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551191/pdf/bmj00618-0070a.pdf

 

Exercise responses and psychiatric disorder in chronic fatigue syndrome

Comment in: Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data. [BMJ. 1995]

 

Fatigue, exercise intolerance, and myalgia are cardinal symptoms of the chronic fatigue syndrome, but whether they reflect neuromuscular dysfunction or are a manifestation of depression or other psychiatric or psychological disorders diagnosed in a high proportion of fatigued patients in the community is unclear.’ In previous studies patients with the chronic fatigue syndrome showed exercise intolerance in incremental exercise tests, which seemed to be related to an increased perception of effort; also, blood lactate concentrations in some patients tended to increase more rapidly than normal at low work rates, implying inefficient aerobic muscle metabolism.2 We examined venous blood lactate responses to exercise at a work rate below the anaerobic threshold in relation to psychiatric disorder.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550606/pdf/bmj00607-0028.pdf

 

Source: Lane RJ, Burgess AP, Flint J, Riccio M, Archard LC. Exercise responses and psychiatric disorder in chronic fatigue syndrome. BMJ. 1995 Aug 26;311(7004):544-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550606/pdf/bmj00607-0028.pdf

 

Chronic fatigue syndrome and fibromyalgia

Comment on: Population study of tender point counts and pain as evidence of fibromyalgia. [BMJ. 1994]

 

EDITOR,-The relation between muscle pain, tender points, the chronic fatigue syndrome, and fibromyalgia are complex, and simplistic answers are inappropriate. In their paper Peter Croft and colleagues extrapolate their results to make two statements that I believe to be incorrect.’

My conclusions are based on 100 consecutive patients seen at Raigmore Hospital NHS Trust, who fulfilled precise definitions of the chronic fatigue syndrome 2 or fibromyalgia.3 The importance of this definition of the syndrome is that it has the same three month cut off for length of illness as fibromyalgia.3 Of the 100 patients, 99 (74 women, 25 men) had the chronic fatigue syndrome and one (a woman) had fibromyalgia. Of the patients with the chronic fatigue syndrome, 63 had muscle pain and 28 had tender points on examination, 23 had both, and five had no muscle pain but tender points. These results do not support the authors’ statement that the reason why fibromyalgia is not more common in Britain has been the acceptability of the chronic fatigue syndrome as an alternative diagnosis.

The authors also say that it is “inappropriate to define an entity as fibromyalgia.” As a clinical virologist, I strongly disagree with this as the distribution and number of tender points in fibromyalgia are different from those in the chronic fatigue syndrome, and the management of the two conditions is different.4 Patients with the syndrome should be advised not to increase their activities gradually until they feel 80% of normal,5 whereas patients with fibromyalgia may benefit from a regimen of increasing activity.4

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541601/pdf/bmj00468-0067b.pdf

 

Source: Ho-Yen DO. BMJ. Chronic fatigue syndrome and fibromyalgia. 1994 Dec 3;309(6967):1515. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541601/

 

Lactate responses to exercise in chronic fatigue syndrome

Comment on: Exercise performance and fatiguability in patients with chronic fatigue syndrome. [J Neurol Neurosurg Psychiatry. 1993]

 

We were interested to read the recent account of exercise characteristics in patients with chronic fatigue syndrome by Gibson et al,’ which concluded that there was no abnormality of neuromuscular function in this condition. Patients reached the limits of exercise tolerance at lower heart rates than controls during incremental exercise to exhaustion but their peak work rates and duration of exercise did not differ significantly from the control group, although the total work done (the product of these variables) would appear to have been less; the authors had previously reported that patients with this condition showed a reduction in maximal work rate achieved in such tests.2 Despite this, plasma lactate levels at the end of exercise were as high in the patients as the controls.

In an earlier study using incremental exercise on a treadmill, Riley et a13 had found higher heart rates and increased lactate levels compared with normal controls at submaximal work rates but similarly noted no differences at peak exercise.

We have found that a proportion of patients with chronic fatigue syndrome exhibit abnormally raised lactate levels following steady state exercise at work rates below the anerobic threshold, corresponding to roughly half the peak work rates achieved in the incremental test paradigm.4 It is thus possible that lactate levels in some patients increase more rapidly than normal at lower work rates.

The cause of this apparent ‘left shift’ of the anaerobic threshold is unclear. Neither we nor Gibson et al 2 found evidence of “deconditioning” in terms of cardiac responses to exercise in our patients, and phosphorus spectroscopy of muscle in the syndrome has shown no consistent disturbance of muscle energy metabolism.5 The phenomenon may be of significance in the pathogenesis of “fatigue” in some patients, and it may be premature to conclude that neuromuscular function in all patients is normal, or that the “fatigue” is exclusively “central” in origin. Indeed, it may be presumptuous to consider chronic fatigue syndrome as a unitary entity.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1072952/pdf/jnnpsyc00035-0134b.pdf

 

Source: Lane RJ, Woodrow D, Archard LC. Lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1994 May;57(5):662-3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1072952/

 

Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients

 

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS.

Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group.

Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.

 

Source: Peterson PK, Sirr SA, Grammith FC, Schenck CH, Pheley AM, Hu S, Chao CC. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Lab Immunol. 1994 Mar;1(2):222-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/pdf/cdli00002-0112.pdf

 

Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise

Abstract:

We have studied the relationship between the cytokine production induced in vivo by prolonged isometric exercise and the symptom complex marked by fatigue in patients with chronic fatigue syndrome (CFS).

Twelve male patients and 13 matched male control subjects undertook an isometric hand-grip exercise protocol utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the target force was set at 40% of the maximal voluntary contraction and the duty cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood samples were collected and assayed for the presence of cytokines, including interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis factor-alpha. At those times subjects also completed the Profile of Mood States (POMS) questionnaire, which served as a measure of changes in subjective fatigue.

No significant alteration in the level of any of the cytokines in the plasma of patients or control subjects was detected before, during, or after exercise. Surprisingly, the patients’ levels of fatigue, depression, and confusion, as measured by the POMS, decreased in response to the exercise.

These data do not confirm the presence of an immunologic process correlating with the exacerbation of fatigue after exercise experienced by patients with CFS. Limitations in the study design and in the sensitivity of the cytokine assays may have affected our results.

 

Source: Lloyd A, Gandevia S, Brockman A, Hales J, Wakefield D. Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise. Clin Infect Dis. 1994 Jan;18 Suppl 1:S142-6. http://www.ncbi.nlm.nih.gov/pubmed/8148442

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214