Tag: acidosis

In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Post-exertional malaise is commonly observed in patients with myalgic encephalomyelitis/chronic fatigue syndrome, but its mechanism is not yet well understood. A reduced capacity for mitochondrial ATP synthesis is associated with the pathogenesis of CFS and is suspected to be a major contribution to exercise intolerance in CFS patients.

To demonstrate the connection between a reduced mitochondrial capacity and exercise intolerance, we present a model which simulates metabolite dynamics in skeletal muscles during exercise and recovery. CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected. To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress. Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations.

Copyright © 2015 Elsevier B.V. All rights reserved.

 

Source: Lengert N, Drossel B. In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Biophys Chem. 2015 Jul;202:21-31. doi: 10.1016/j.bpc.2015.03.009. Epub 2015 Apr 4. https://www.ncbi.nlm.nih.gov/pubmed/25899994

 

Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.

METHODS: A total of 18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

RESULT: Chronic fatigue syndrome patients undertaking MVC fell into two distinct groups: 8 (45%) showed normal PCr depletion in response to exercise at 35% of MVC (PCr depletion >33%; lower 95% CI for controls); 10 CFS patients had low PCr depletion (generating abnormally low MVC values). The CFS whole group exhibited significantly reduced anaerobic threshold, heart rate, VO(2) , VO(2) peak and peak work compared to controls. Resting muscle pH was similar in controls and both CFS patient groups. However, the CFS group achieving normal PCr depletion values showed increased intramuscular acidosis compared to controls after similar work after each of the three exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This CFS group also exhibited significant prolongation (almost 4-fold) of the time taken for pH to recover to baseline.

CONCLUSION: When exercising to comparable levels to normal controls, CFS patients exhibit profound abnormality in bioenergetic function and response to it. Although exercise intervention is the logical treatment for patients showing acidosis, any trial must exclude subjects who do not initiate exercise as they will not benefit. This potentially explains previous mixed results in CFS exercise trials.

© 2011 The Authors. European Journal of Clinical Investigation

© 2011 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study. Eur J Clin Invest. 2012 Feb;42(2):186-94. doi: 10.1111/j.1365-2362.2011.02567.x. Epub 2011 Jul 12. https://www.ncbi.nlm.nih.gov/pubmed/21749371

 

In vivo magnetic resonance spectroscopy in chronic fatigue syndrome

Abstract:

The pathogenic mechanisms of chronic fatigue syndrome (CFS) are not clearly known. Fatigue, poor short-term memory and muscle pain are the most disabling symptoms in CFS. Research data on magnetic resonance spectroscopy (MRS) of muscles and brain in CFS patients suggest a cellular metabolic abnormality in some cases.

31P MRS of skeletal muscles in a subset of patients indicate early intracellular acidosis in the exercising muscles. 1H MRS of the regional brain areas in CFS have shown increased peaks of choline derived from the cell membrane phospholipids.

Cell membrane oxidative stress may offer a common explanation for the observed MRS changes in the muscles and brain of CFS patients and this may have important therapeutic implications. As a research tool, MRS may be used as an objective outcome measure in the intervention studies. In addition, regional brain 1H MRS has the potential for wider use to substantiate a clinical diagnosis of CFS from other disorders of unexplained chronic fatigue.

 

Source: Chaudhuri A, Behan PO. In vivo magnetic resonance spectroscopy in chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):181-3. http://www.ncbi.nlm.nih.gov/pubmed/15253888

 

Effort syndrome: hyperventilation and reduction of anaerobic threshold

Abstract:

Effort syndrome is an entity in danger of being subsumed into “chronic fatigue syndrome” and lost to sight. Its distinctive feature is the reduction of the anaerobic threshold for work by depletion of the body’s alkaline buffering systems through hyperventilation. This article describes the history and clinical features of effort syndrome and reports a study in which capnography is used to identify the anaerobic threshold by registering the respiratory response to the onset of metabolic acidosis. The patients’ thresholds are low, and provide a goal for rehabilitation. In other forms of chronic fatigue syndrome, the pathogenesis and logic of therapy are unclear.

 

Source: Nixon PG. Effort syndrome: hyperventilation and reduction of anaerobic threshold. Biofeedback Self Regul. 1994 Jun;19(2):155-69. http://www.ncbi.nlm.nih.gov/pubmed/7918753

 

Aerobic work capacity in chronic fatigue syndrome

Comment on Aerobic work capacity in patients with chronic fatigue syndrome. [BMJ. 1990]

SIR,

The data of Dr Marshall S Riley and colleagues (1) are consistent with our findings (2) that most patients referred with the chronic fatigue syndrome have the effort syndrome-that is, chronic hyperventilation as a consequence of excessive effort and distress.(3)

May we draw attention to three points. Dr Riley and colleagues concluded that the patients could not be hyperventilating because their values of end-tidal partial pressure of carbon dioxide at rest and at peak exercise did not differ significantly from those of the controls.

In our opinion the values published for the controls (35 8 mmHg at rest and 36-3 mmHg at peak exercise) are too low to be accepted as normal. The finding that the patients reached their anaerobic threshold far quicker than did the controls is consistent with the early acidosis on exertion known to occur in chronic hyperventilation. This is a consequence of the depletion of the body’s buffer base reserves,(4) brought about by renal compensation for chronic respiratory alkalosis.(5)

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664329/pdf/bmj00207-0055b.pdf

 

Source: Rosen SD, King JC, Wilkinson JB, Nixon PG. Aerobic work capacity in chronic fatigue syndrome. BMJ. 1990 Nov 24;301(6762):1217. [Comment] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664329/

 

Myalgic encephalomyelitis

Note: This letter appeared in the Journal of the Royal Society of Medicine in March 1990.

 

We accept that Martin Lev (November 1989 JRSM, p 693) is correct to point out that the anxiety and depression noted in patients labelled as suffering from ‘ME’ are the consequence of ‘underlying organic processes’. The demonstration of hyperventilation in the overwhelming majority of these patients (Rosen SD, King JC, Nixon PGF, unpublished results), provides a clear metabolic reason for the anxiety (1-3). ‘Depression’ is a predictable reaction to the inability to make and sustain effort due in part to the ease of acidosis of muscle cells depleted of buffer base reserves(4).

We agree with Sargant(5), that the sufferers from the late stages of effort syndrome, who have nothing to gain from their ill health and much to lose, are among the most gifted and energetic of people, and consequently the most upset about the frustration caused by loss of performance.

~S D ROSEN Cardiac Registrar

~J C KING Honorary Head Occupational Therapist (Research)

~P G F NIXON Consultant Cardiologist Charing Cross Hospital London

 

 References

1 Lewis T, et al. Breathlessness in soldiers suffering from irritable heart. Br Med J 14 October 1916:517-19

2 Lum LC. The syndrome of chronic habitual hyperventilation. In: Hill OW, ed. Modern trends in psychosomatic medicine, vol. 3. London: Butterworths, 1976: 196-230

3 Groen JJ. The measurement of emotion and arousal in the clinical physiological laboratory and in medical practice. In: Levi L, ed. The emotions: their parameters and measurement. New York: Raven Press, 1975:727-46

4 Rosen SD, King JC, Nixon PGF. Magnetic resonance muscle studies. J R Soc Med 1988;81:676-7 5 Sargant W. Battle for the mind Aphysiology ofconversion and brain-washing. London: Heinemann 1957

 

Source:  Rosen, SD, King, JC, Nixon, PGF. Myalgic encephalomyelitis. Journal of the Royal Society of Medicine Volume 83 March 1990.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292587/