Tag: hyperventilation

Carotid body dysregulation contributes to the enigma of long COVID

Abstract:

The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID. During cardiopulmonary exercise testing, the VE/VCO2 slope (a measure of breathing efficiency) was higher in the long COVID group than in the controls, indicating excessive hyperventilation.

The hypoxic ventilatory response, which measures carotid chemoreflex sensitivity, was increased in long COVID participants and correlated with the VE/VCO2 slope, suggesting that excessive hyperventilation may be related to carotid body hypersensitivity. Therefore, the carotid chemoreflex is sensitized in long COVID and may explain dysregulated breathing and exercise intolerance in these participants. Tempering carotid body excitability may be a viable treatment option for long COVID patients.

Source: Ahmed El-Medany, Zoe H Adams, Hazel C Blythe, Katrina A Hope, Adrian H Kendrick, Ana Paula Abdala Sheikh, Julian FR Paton, Angus K Nightingale, Emma C Hart. Carotid body dysregulation contributes to the enigma of long COVID. medRxiv 2023.05.25.23290513; doi: https://doi.org/10.1101/2023.05.25.23290513 https://www.medrxiv.org/content/10.1101/2023.05.25.23290513v1.full-text (Full text)

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach

Abstract:

Dyspnea, shortness of breath, and chest pain are frequent symptoms of post-COVID syndrome (PCS). These symptoms are unrelated to organ damage in most patients after mild acute COVID infection. Hyperventilation has been identified as a cause of exercise-induced dyspnea in PCS. Since there is a broad overlap in symptomatology with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), causes for dyspnea and potential consequences can be deduced by a stringent application of assumptions made for ME/CFS in our recent review papers.

One of the first stimuli of respiration in exercise is caused by metabolic feedback via skeletal muscle afferents. Hyperventilation in PCS, which occurs early on during exercise, can arise from a combined disturbance of a poor skeletal muscle energetic situation and autonomic dysfunction (overshooting respiratory response), both found in ME/CFS. The exaggerated respiratory response aggravating dyspnea does not only limit the ability to exercise but further impairs the muscular energetic situation: one of the buffering mechanisms to respiratory alkalosis is a proton shift from intracellular to extracellular space via the sodium-proton-exchanger subtype 1 (NHE1), thereby loading cells with sodium. This adds to two other sodium loading mechanisms already operative, namely glycolytic metabolism (intracellular acidosis) and impaired Na+/K+ATPase activity.

High intracellular sodium has unfavorable effects on mitochondrial calcium and metabolism via sodium-calcium-exchangers (NCX). Mitochondrial calcium overload by high intracellular sodium reversing the transport mode of NCX to import calcium is a key driver for fatigue and chronification. Prevention of hyperventilation has a therapeutic potential by keeping intracellular sodium below the threshold where calcium overload occurs.

Source: Wirth KJ, Scheibenbogen C. Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach. Medicina (Kaunas). 2022 Mar 12;58(3):419. doi: 10.3390/medicina58030419. PMID: 35334595. https://www.mdpi.com/1648-9144/58/3/419/htm (Full text)

Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) with orthostatic intolerance is characterized by neurocognitive deficits and impaired working memory, concentration, and information processing. In CFS, upright tilting [head-up tilt (HUT)] caused decreased cerebral blood flow velocity (CBFv) related to hyperventilation/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition.

We loaded the baroreflex with phenylephrine to prevent hyperventilation and performed n-back neurocognition testing in 11 control subjects and 15 CFS patients. HUT caused a significant increase in heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decrease in end-tidal CO2 (ETCO2; 42.8 ± 1.2 vs. 33.9 ± 1.1 Torr, P < 0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in control subjects but fell 22.5% in CFS.

In CFS, phenylephrine prevented the HUT-induced hyperventilation/hypocapnia and the significant drop in CBFv with HUT (-8.1% vs. -22.5% untreated). There was no difference in control subject n-back normalized response time (nRT) comparing supine to HUT (106.1 ± 6.9 vs. 97.6 ± 7.1 ms at n = 4), and no difference comparing control to CFS while supine (97.1 ± 7.1 vs 96.5 ± 3.9 ms at n = 4). However, HUT of CFS subjects caused a significant increase in nRT (148.0 ± 9.3 vs. 96.4 ± 6.0 ms at n = 4) compared with supine.

Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6 ± 7.1 vs. 114.6 ± 9.3 ms at n = 4). Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing blood pressure with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on n-back outcome.

Copyright © 2014 the American Physiological Society.

 

Source: Medow MS, Sood S, Messer Z, Dzogbeta S, Terilli C, Stewart JM. Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome. J Appl Physiol (1985). 2014 Nov 15;117(10):1157-64. doi: 10.1152/japplphysiol.00527.2014. Epub 2014 Oct 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233252/ (Full article)

 

Hyperventilation in patients with chronic fatigue syndrome: the role of coping strategies

Abstract:

Hyperventilation has been suggested as a concomitant and possible maintaining factor that may contribute to the symptom pattern of chronic fatigue syndrome (CFS). Because patients accepting the illness and trying to live with it seem to have a better prognosis than patients chronically fighting it, we investigated breathing behavior during different coping response sets towards the illness in patients with CFS (N=30, CDC criteria).

Patients imagined a relaxation script (baseline), a script describing a coping response of hostile resistance, and a script depicting acceptance of the illness and its (future) consequences. During each imagery trial, end-tidal PCO2 (Handheld Capnograph, Oridion) was measured. After each trial, patients filled out a symptom checklist. Results showed low resting values of PetCO2 overall, while only imagery of hostile resistance triggered a decrease and deficient recovery of PetCO2. Also, more hyperventilation complaints and complaints of other origin were reported during hostile resistance imagery compared with acceptance and relaxation.

In conclusion, hostile resistance seems to trigger both physiological and symptom perception processes contributing to the clinical picture of CFS.

 

Source: Bogaerts K, Hubin M, Van Diest I, De Peuter S, Van Houdenhove B, Van Wambeke P, Crombez G, Van den Bergh O. Hyperventilation in patients with chronic fatigue syndrome: the role of coping strategies. Behav Res Ther. 2007 Nov;45(11):2679-90. Epub 2007 Jul 20. https://www.ncbi.nlm.nih.gov/pubmed/17719001

 

The chronic fatigue syndrome and hyperventilation

Erratum in: J Psychosom Res 1998 Mar-Apr;44(3-4):517.

 

Abstract:

Chronic fatigue syndrome (CFS) is characterized by severe fatigue, lasting for at least 6 months, for which no somatic explanation can be found. Because hyperventilation can produce substantial fatigue, it seems worthwhile to investigate the relationship between it and CFS. It might be hypothesized that hyperventilation plays a causal or perpetuating role in CFS.

CFS patients, non-CFS patients known to experience hyperventilation, and healthy controls were compared on complaints of fatigue and hyperventilation. CFS patients and non-CFS patients known to experience hyperventilation offered substantial complaints of fatigue and hyperventilation, both to a similar degree. Physiological evidence of hyperventilation was found significantly more often in CFS patients than in healthy controls.

However, no significant differences between CFS patients with and CFS patients without hyperventilation were found on severity of fatigue, impairment, number of complaints, activity level, psychopathology, and depression. It is concluded that hyperventilation in CFS should probably be regarded as an epiphenomenon.

 

Source: Bazelmans E, Bleijenberg G, Vercoulen JH, van der Meer JW, Folgering H. The chronic fatigue syndrome and hyperventilation. J Psychosom Res. 1997 Oct;43(4):371-7. http://www.ncbi.nlm.nih.gov/pubmed/9330236

 

Brainstem hypoperfusion in CFS

Comment on: Brainstem perfusion is impaired in chronic fatigue syndrome. [QJM. 1995]

 

Sir, Costa and his colleagues {QJ Med 1995; 88:767-73) are to be congratulated for providing more information about chronic fatigue syndrome. Hypocapnia is a powerful and readily available cerebral vasoconstrictor.1

The ‘cerebral vasoconstriction, and reduction in cerebral blood flow, are initiated when the arterial pCO2 has fallen 2 mmHg below normal. When the pCO2 has fallen by 25 mmHg, cerebral blood flow is decreased by about one third … the maximum possible reduction of blood flow that can be achieved by respiratory alkalaemia is of the order of 40 per cent’.2

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/89/2/163.1.long

 

Source: Nixon PG. Brainstem hypoperfusion in CFS. QJM. 1996 Feb;89(2):163-4. http://qjmed.oxfordjournals.org/content/89/2/163.1.long

 

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

 

Hyperventilation and chronic fatigue syndrome

Abstract:

We studied the link between chronic fatigue syndrome (CFS) and hyperventilation in 31 consecutive attenders at a chronic fatigue clinic (19 females, 12 males) who fulfilled criteria for CFS based on both Oxford and Joint CDC/NIH criteria. All experienced profound fatigue and fatigability associated with minimal exertion, in 66% developing after an infective episode. Alternative causes of fatigue were excluded.

Hyperventilation was studied during a 43-min protocol in which end-tidal PCO2 (PETCO2) was measured non-invasively by capnograph or mass spectrometer via a fine catheter taped in a nostril at rest, during and after exercise (10-50 W) and for 10 min during recovery from voluntary overbreathing to approximately 2.7 kPa (20 mmHg). PETCO2 < 4 kPa (30 mmHg) at rest, during or after exercise, or at 5 min after the end of voluntary overbreathing, suggested either hyperventilation or a tendency to hyperventilate. Most patients were able voluntarily to overbreathe, but not all were able to exercise.

Twenty-two patients (71%) had no evidence of hyperventilation during any aspect of the test. Only four patients had unequivocal hyperventilation, in one associated with asthma and in three with panic. Only one patient with severe functional disability and agoraphobia had hyperventilation with no other obvious cause. A further five patients had borderline hyperventilation, in which PETCO2 was < 4 kPa (30 mmHg) for no more than 2 min, when we would have expected it to be normal. There was no association between level of functional impairment and degree of hyperventilation. There is only a weak association between hyperventilation and chronic fatigue syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Comment in: Hyperventilation and the chronic fatigue syndrome. [Q J Med. 1994]

Source: Saisch SG, Deale A, Gardner WN, Wessely S. Hyperventilation and chronic fatigue syndrome. Q J Med. 1994 Jan;87(1):63-7. http://www.ncbi.nlm.nih.gov/pubmed/8140219

 

The grey area of effort syndrome and hyperventilation: from Thomas Lewis to today

Abstract:

Lewis used the diagnosis ‘effort syndrome’ for subjects whose ability to make and sustain effort had been reduced by homeostatic failure. A major element was depletion of the body’s capacity for buffering the acids produced by exercise.

In his view this systems disorder was not to be regarded as a specific organ disease, and losing sight of the metabolic element would foster the invention of fanciful, unphysiological diagnoses. His views were dismissed because normal resting plasma bicarbonate levels were considered by others in that era to exclude serious depletion of the body’s total capacity for buffering the effects of exertion.

Today, effort syndrome is still a useful diagnosis for a condition of exhaustion and failure of performance associated with depletion of the body’s buffering systems. Other elements associated with homeostatic failure are now recognised, principally emotional hyperarousal and hyperventilation. Their physiological interrelationships are described. Effort syndrome is amenable to recovery through rehabilitation, and it may be a mistake to treat chronic fatigue syndrome and unspecific illness without including it in the differential diagnosis.

 

Source: Nixon PG. The grey area of effort syndrome and hyperventilation: from Thomas Lewis to today. J R Coll Physicians Lond. 1993 Oct;27(4):377-83. http://www.ncbi.nlm.nih.gov/pubmed/8289156

 

Is chronic fatigue syndrome synonymous with effort syndrome?

Abstract:

Chronic fatigue syndrome (CFS), including myalgic encephalomyelitis (ME) and postviral syndrome (PVS), is a term used today to describe a condition of incapacity for making and sustaining effort, associated with a wide range of symptoms. None of the reviews of CFS has provided a proper consideration of the effort syndrome caused by chronic habitual hyperventilation.

In 100 consecutive patients, whose CFS had been attributed to ME or PVS, the time course of their illness and the respiratory psychophysiological studies were characteristic of chronic habitual hyperventilation in 93.

It is suggested that the labels ‘CFS’, ‘ME’ or ‘PVS’ should be withheld until chronic habitual hyperventilation – for which conventional rehabilitation is available – has been definitively excluded.

 

Source: Rosen SD, King JC, Wilkinson JB, Nixon PG. Is chronic fatigue syndrome synonymous with effort syndrome? J R Soc Med. 1990 Dec;83(12):761-4. http://www.ncbi.nlm.nih.gov/pubmed/2125315