ME/CFS, FM: Mitochondrial dysfunction ... cellular hypoxia, hypoperfusion, endothelial dysfunction, persistent clots, 2021, Chang, Figueredo

Preprint
ME/CFS, FM: Mitochondrial dysfunction in diseases presenting chronic fatigue and brain fog is associated with cellular hypoxia, hypoperfusion, endothelial dysfunction and persistent clots.

Abstract
Analysis of Venous Blood Gases, Lactate and D-Dimer is recommended in patients with Chronic Fatigue, Persistent Symptoms of COVID (Long COVID), Fibromyalgia, Chronic Lyme, Herpesvirus, EBV, Bartonela, Babesia, Enterovirus, HPV, Parvovirus, Anaplasmosis, Disease of the Gulf War, Alzheimer's and others.

Cellular Hypoxia causes Mitochondrial Dysfunction.
In a state of normal oxygenation, the cells maintain an aerobic metabolism since the supply of oxygen meets the demand of the cells and tissues. But in a state of hypoxia, when aerobic metabolism is insufficient to produce Adenosine Triphosphate (ATP), cells must resort to alternative pathways to maintain ATP production, which is why anaerobic metabolism is activated, which is not efficient in generating the energy (ATP) required by the body, so the little amount of ATP that is generated by the anaerobic route, is depleted or consumed rapidly during activities. ATP is the main source of energy for the cells of living organisms, and it is necessary for almost all forms of biological work, such as muscle contraction, digestion, nerve transmission, gland secretion, etc.

Diagnosis of Hypoxemia by measuring Venous Blood Gases.
An accessible and inexpensive diagnostic aid test is the Venous Oxygen Saturation (SvO2 or Sat vO2) blood test, for which the patient is required to request a Venous Gas Measurement, and that SvO2 is part of the results reported with this test (1,2). The Venous Gas test is also known as Venous Gasometry, or Measurement of Venous Blood Gases or Gases of the Veins. Its cost is between 30 to 45 US dollars. Venous Blood Oxygen Saturation (SvO2) is also known as Mixed Venous Oxygen Saturation, or Peripheral Venous Saturation.

Interpretation of a low SvO2 value (Hypoxemia).
SvO2 gives us the value of the percentage of oxygen bound to hemoglobin in the blood when it returns to the heart. SvO2 is a reflection of how the oxygen saturation level is in all the venous blood of the body, and before it returns to be re-oxygenated at the heart level with the oxygen obtained in the lungs. A low SvO2 value indicates that there is less oxygen in the venous blood, this is called Hypoxemia. By extrapolation, it is used as a marker of the way in which oxygen is supplied to the cells and tissues of the organism, so a low value of SvO2 is correlated with the existence of cellular hypoxia, and is associated with tissue hypoperfusion. Normal Venous Oxygen Saturation Values (SvO2). In most laboratories and hospitals, the generally accepted normal value,for a Venous Oxygen Saturation (SvO2) for the optimal functioning of the organism, it is 70% or more.

Low and Very Low SvO2 Values.
As long as the SvO2 does not fall below 50%, it is indicated that an adapted or compensated hypoxia occurs, in which the cells can still maintain practically all their functions without generating an obvious alteration. We consider a value of 30 to 49% of SvO2 to be a very low value of SvO2. According to our experience with the evaluated patients, those who present Moderate to severe fatigue and brain fog, a SvO2 result of between 30 to 45% is usually found, and with the established treatments the values improve significantly.

Dysoxia with higher production of Lactate and Pyruvate.
It is considered that when SvO2 drops to less than 50% and persists in these low oxygenation levels, Dysoxia occurs, which is a state of cellular hypoxia in which ATP production is limited by the very low level of oxygen, so "mitochondrial respiration" cannot be maintained, mitochondrial dysfunction occurs, ATP production decreases and existing ATP depletion occurs, this situation of cellular hypoxia causes the body to resort to increasing lactate production (or lactic acid) from pyruvate, so the blood levels of lactate (hyperlactacidemia) and pyruvate rise.

Lactate or Lactic Acid Measurement.
As with some frequency, Mild and Moderate cases of patients with chronic fatigue and mental fog may present normal SvO2 values, it is indicated that in addition to the measurement of Venous Gases, patients should be asked for Lactate blood tests. If a lactate level is found above normal, this would indicate that there is cellular hypoxia.

Lactate (or Lactic Acid) sampling procedure.
The blood sampling procedure for the lactate (or lactic acid) test is similar to the procedure for routine blood tests, that is, a small blood sample is taken from a vein of one of the the patient's arms and does not need to be fasting. What is indicated is that, in the 12 to 24 hours prior to the analysis, the patient avoid making greater physical efforts than usual (for example, walking a long distance or exercising), especially if they have muscle pain after exertion. The cost of this analysis is between 18 to 36 US dollars.

Normal and high Lactate values.
Most of the publications consider that the normal value of lactate in the blood (serum) is between 0.5 and 1.4 mmol/L, but a study that included 7,155 critically ill patients hospitalized in the ICU concluded that it was advisable to consider a higher risk when lactate is it is above 0.75 mmol/L in critically ill patients (3,4), therefore, we propose to consider a normal value of lactate between 0.5 to 0.9; from 1.0 to 1.4 should be considered as an intermediate level between the normal level and the high level of lactose, and from 1.5 we consider that the lactate is elevated, and the term hyperlactacidemia is used to refer to a value above normal

Hyperlactacidemia with lactic acidosis.
As the lactate or lactic acid rises in the blood, the pH goes down, and when the pH falls below 7.35 it is established that there is Acidemia that causes Acidosis, this occurs when the Lactate rises to between 4 to 5 mmol/L.

Interpretation of a high value of Lactate.
In patients with CFS/ME, Chronic or Persistent COVID and other diseases that present symptoms of Chronic Fatigue and Mental Fog, finding a high value of Lactate is associated with the presence of cellular hypoxia, a condition in which there is an increase in the production of lactate and pyruvate. Cellular hypoxia associated with Hypoxemia and Hypoperfusion. If the lactate is elevated, in addition to cellular hypoxia, it is interpreted that there is Hypoxemia and a degree of relevant tissue Hypoperfusion, that is, that there is a dysfunction and/or a physical barrier at the level of the walls of the blood vessels that limits the passage of oxygen from the blood to the cells and tissues of the body, and this situation would be what would cause the symptoms of Chronic Fatigue and Brain Fog.

Chronic Fatigue and Brain Fog are associated with dysfunction of the endothelial cells of the blood vessels and tissue hypoperfusion.
Several studies have been published in which it is evidenced that, both in Chronic Fatigue Syndrome (CFS) and in patients with Brain Fog, there is a persistent dysfunction of the endothelial cells of the blood vessels, and there are also studies that show less blood flow and hypoperfusion towards the cells and tissues of the body (5-9).

Persistent high fibrin clots.
For our part, in previous publications we have explained that Chronic Fatigue and Brain Fog present in Chronic Fatigue Syndrome (CFS), in Persistent Symptoms of COVID and in other Chronic Diseases associated with Persistent Intracellular Infections, are associated with platelet hyperactivity, persistent dysfunction of endothelial cells and pericytes, reduction of endothelial glycocalyx, presence of persistent clots and alterations in blood cells (10-12). According to our approach, in almost all patients with chronic fatigue there is long-term dysfunction of the blood vessels, and this is accompanied by an increase in the density of the blood and the presence of persistent clots with high fibrin content and that are attached to the vascular walls and are also circulating intravascularly as part of the bloodstream. There have already been publications in which the presence of persistent clots is evidenced in patients with Chronic or Persistent COVID (13,14), and in patients who are undergoing HELP Apheresis clots are macroscopically evident, which frequently adhere to the cannulas and filters used in this procedure.

 

Gustavo Chang: National University of San Marcos is in Lima, Peru

This may be why Professor Pretorius specifically warned against taking aspirin.


Aurora Figueredo:SIGESA