Excessive Intracellular Acidosis Of Skeletal Muscle On Exercise [in] Post-Viral Exhaustion/Fatigue Syndrome: A 31P [NMR] Study, 1984, Arnold et al.

SNT Gatchaman · Jan 13, 2024

Excessive Intracellular Acidosis Of Skeletal Muscle On Exercise In A Patient With A Post-Viral Exhaustion/Fatigue Syndrome: A 31P Nuclear Magnetic Resonance Study
Arnold; Radda; Bore; Styles; Taylor

A patient with prolonged post-viral exhaustion and excessive fatigue was examined by 31P nuclear magnetic resonance.

During exercise, muscles of the forearm demonstrated abnormally early intracellular acidosis for the exercise performed. This was out of proportion to the associated changes in high-energy phosphates.

This may represent excessive lactic acid formation resulting from a disorder of metabolic regulation. The metabolic abnormality in this patient could not have been demonstrated by traditional diagnostic techniques.

Link | Paywall (The Lancet)

SNT Gatchaman · Jan 13, 2024

Historical paper for future reference.

Simon M · Jan 13, 2024

Are these Newton papers relevant? I haven't looked at them for years and you might well be aware of them in any case. I'm not sure this work was ever followed up properly.
https://scholar.google.co.uk/scholar?q=newton+cfs+31-p&hl=en&as_sdt=0&as_vis=1&oi=scholart

SNT Gatchaman · Jan 13, 2024

SNT Gatchaman · Jan 13, 2024

Simon M said: ↑

Are these Newton papers relevant? I haven't looked at them for years and you might well be aware of them in any case. I'm not sure this work was ever followed up properly.
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Thanks Simon - I'll have a look through. I thought it was worth having the early work more accessible given the recent LC muscle findings and the upcoming ME/CFS replication indicated by the Dutch team.

SNT Gatchaman · Jan 13, 2024

Introduction

A small number of patients complain that they never recover from the exhaustion and fatigue associated with a viral illness. Investigation of these patients often fails to provide an explanation for their symptoms, although detailed investigations may reveal abnormalities in electrophysiologi-cal studies and in tests relating to the function of the immune system (Behan PO, Behan WMH, Bell EJ. Unpublished).
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We report here the 31P nuclear magnetic resonance (NMR) examination of one such patient who demonstrated excessive intracellular acidosis of muscle fibres during exercise. This biochemical abnormality may provide some insight into the pathogenesis of the symptoms of this condition.
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SNT Gatchaman · Jan 13, 2024

Case Report

A 30-year-old general practitioner had been in good health until an attack of chickenpox at age 26 which was accompanied by a confusional state. Recovery was never complete, and the patient was left with a general malaise. He was easily fatigued, both physically and mentally, and had a persistent feeling of unsteadiness. These symptoms eventually forced him to give up his practice. Moderate activity (eg, walking a mile) would result in exhaustion and muscle pain such as would normally follow much more severe exercise.
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The patient was not seen during the acute illness. However, he subsequently consulted several neurologists and was admitted to hospital on three occasions. Physical examination of the motor system was unremarkable. Electroencephalography showed asymmetrical theta activity over the left frontotemporal region with hyperventilation only. Electronystagmography was interpreted as being indicative of vestibulo-cerebellar dysfunction. Serum creatine kinase (CPK) was never outside the normal range, but single fibre electromyography showed increased jitter without blocking.
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Immunological investigation revealed decreased numbers of helper/inducer cells, almost total unresponsiveness to stimulation by phytohaemagglutinin, and raised concentration of circulating immune complexes. Muscle biopsy showed scattered necrotic fibres and type II fibre predominance. There was no evidence of inflammation.
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SNT Gatchaman · Jan 13, 2024

Results

Our studies have demonstrated a consistent relation in healthy subjects between changes in Iphosphocreatine] and intracellular pH during a standard aerobic exercise described above. Figure la demonstrates the abnormally early, severe intracellular acidosis in the forearm muscle of this patient during exercise. Intracellular pH decreased to 6.3 during the first 5 min of relatively mild exercise, despite changes in [phosphocreatine] similar to those in controls and normally associated with an intracellular pH above 6.80.
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The relation between the intracellular pH changes and the concentration of phosphocreatine is shown in figure lb. The patient acidifies his muscles excessively in relation to the decrease in phosphocreatine concentration during exercise.
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The time course of recovery of [phosphocreatine] after exercise is shown in fig 2. Although this was somewhat slower than that observed in healthy controls after the same exercise protocol, recovery of calculated free [ADP] after exercise was not abnormally slow. Intracellular pH returned to resting values by 0.06 pH units/min in the linear range. This was normal for the exercise protocol.
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Results for the patient represent the mean+SEM of 4 separate exercise tests on two different days, several months apart. Studies done on the same day were separated by an interval of at least 2 hours. Control values shown are the mean+SEM for 8 healthy subjects.
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SNT Gatchaman · Jan 13, 2024

Discussion

It has been suggested that intracellular acidosis is associated with muscle fatigue., Therefore, the early excessive acidosis during exercise demonstrated by 31P NMR in this patient may be associated with his symptoms of exhaustion and becoming easily fatigued. Since his symptoms started after a viral illness, it is tempting to implicate this infection in the abnormal metabolic response to exercise.
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Acidification of muscle during exercise is the result of lactic acid formation. Does the abnormal acidosis in this case reflect excessive lactic acid formation or a diminished ability to handle an acid load due either to reduced buffering capacity or impaired acid extrusion. The low intracellular pH which developed soon after the start of mild exercise and the relatively normal pH later in the protocol as the exercise intensity was increased suggests that sarcoplasmic buffering capacity was not inadequate. The normal rate of pH recovery after exercise makes impaired elimination of acid from the muscle cell unlikely.
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We speculate, therefore, that the defect may invole the regulation of the relative contributions of glycolytic and oxidative processes to muscle energy provision. The slow phosphocreatine recovery suggests an aerobic defect, but intracellular pH fell to very low values on two of the four exercise tests and this in itself has been shown to delay phosphocreatine recovery.' If we accept that cytosolic [ADP] reflects mitochondrial oxidative function, 10,11 then the normal [ADP] after exercise suggests that our patient may have excessive glycolytic activity rather than inadequate oxidative metabolism. The predominance of type II fibres is consistent with this.
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Discussion of mechanisms by which a viral infection might have produced these abnormalities would be entirely speculative at this stage. However, there are examples of disturbances in energy metabolism after viral illness. An antibody to mitochondrial ATPase has been found in patients with viral myocarditis!2 and myoadenylate deaminase deficiency has apparently developed after a viral illness.
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The 31P NMR findings in this patient are compatible with what may be emerging as a newly identifiable mechanism of disease. The abnormality in our patient would probably not have been identified by traditional methods.
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Dolphin · Jan 13, 2024

This was on Dr Charles Shepherd, longtime medical advisor and trustee of the (UK) ME Association.

Sid · Jan 14, 2024

Was this ever followed up on to find out if anyone other than CS has the same abnormality?

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Excessive Intracellular Acidosis Of Skeletal Muscle On Exercise [in] Post-Viral Exhaustion/Fatigue Syndrome: A 31P [NMR] Study, 1984, Arnold et al.

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Excessive Intracellular Acidosis Of Skeletal Muscle On Exercise [in] Post-Viral Exhaustion/Fatigue Syndrome: A 31P [NMR] Study, 1984, Arnold et al.

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Simon M Senior Member (Voting Rights)

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