Tag: vasodilation

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

Abstract:

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a chronic multisystem disease characterized by severe muscle fatigue, pain, dizziness, and brain fog. The two most common symptoms are post-exertional malaise (PEM) and orthostatic intolerance (OI). ME/CFS patients with OI (ME+OI) suffer from dizziness or faintness due to a sudden drop in blood pressure while maintaining an upright posture. Clinical research has demonstrated that patients with OI display severe cardiovascular abnormalities resulting in reduced effective blood flow in the cerebral blood vessels. However, despite intense investigation, it is not known why the effective cerebral blood flow is reduced in OI patients. Based on our recent findings, we observed that tetrahydrobiopterin (BH4) metabolism was highly dysregulated in ME+OI patients. In the current review article, we attempted to summarize our recent findings on BH4 metabolism to shed light on the molecular mechanisms of OI.

Source: Rahman AFMT, Benko A, Bulbule S, Gottschalk CG, Arnold LA, Roy A. Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe? Biomolecules. 2025 Jan 10;15(1):102. doi: 10.3390/biom15010102. PMID: 39858496; PMCID: PMC11763651. https://pmc.ncbi.nlm.nih.gov/articles/PMC11763651/ (Full text)

The Cardiac Output-Cerebral Blood Flow Relationship Is Abnormal in Most Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with a Normal Heart Rate and Blood Pressure Response During a Tilt Test

Abstract:

Introduction: Orthostatic intolerance is highly prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), the regulation of CBF is complex and cardiac output (CO) is an important determinant of CBF: a review showed that a 30% reduction in CO results in a 10% reduction in CBF. In previous and separate ME/CFS studies, we showed that CO and CBF decreased to a similar extent during tilt testing.

The aim of the study: to test the relationship between CBF and CO, which seems to be abnormal in ME/CFS patients and is different from that in HCs.

Methods: In this retrospective study we analyzed this relationship in a large group of patients. To compare the patient data with those of HCs, we focused on patients with a normal heart rate (HR) and blood pressure (BP) response to upright tilt. Also, the influence of clinical data was analyzed. A total of 534 ME/CFS patients and 49 HCs underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO2. To measure CBF, extracranial Doppler flow velocity and vessel diameters were obtained using a GE echo system. The same device was used to measure suprasternal aortic flow velocities. End-tidal PCO2 was recorded using a Nonin Lifesense device.

Results: In 46 (9%) patients, CO and CBF changes were in the normal range for HCs, and in 488 (91%) an abnormal CO and CBF reduction was found. In patients with abnormal CO and CBF reductions, the slope of the regression line of CO versus CBF reduction was almost 1. The multiple regression analysis of the latter group showed that the CO reduction for the most part predicted the CBF reduction, with a limited role for the PETCO2 reduction.

Conclusions: Two different patient groups with a normal HR and BP response during the tilt were identified: those with a CO and CBF in the normal range for HCs and those with an abnormal CO and CBF reduction during the tilt (91% of patients). In the latter group of patients, an almost 1:1 relationship between the CO and CBF reduction suggests the absence of compensatory vasodilation in the cerebral vasculature. This might indicate endothelial dysfunction in most ME/CFS patients and may have clinical and therapeutic implications.

Source: van Campen CLMC, Verheugt FWA, Rowe PC, Visser FC. The Cardiac Output-Cerebral Blood Flow Relationship Is Abnormal in Most Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with a Normal Heart Rate and Blood Pressure Response During a Tilt Test. Healthcare (Basel). 2024 Dec 20;12(24):2566. doi: 10.3390/healthcare12242566. PMID: 39765993. https://www.mdpi.com/2227-9032/12/24/2566 (Full text)

Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Evidence is emerging that individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may suffer from chronic vascular dysfunction as a result of illness-related oxidative stress and vascular inflammation. The study aimed to examine the impact of maximal-intensity aerobic exercise on vascular function 48 and 72 h into recovery.

Methods: ME/CFS (n = 11) with gender and age-matched controls (n = 11) were randomly assigned to either a 48 h or 72 h protocol. Each participant had measures of brachial blood pressure, augmentation index (AIx75, standardized to 75 bpm) and carotid-radial pulse wave velocity (crPWV) taken. This was followed by a maximal incremental cycle exercise test. Resting measures were repeated 48 or 72 h later (depending on group allocation).

Results: No significant differences were found when ME/CFS were directly compared to controls at baseline. During recovery, the 48 h control group experienced a significant 7.2% reduction in AIx75 from baseline measures (p < 0.05), while the matched ME/CFS experienced no change in AIx75. The 72 h ME/CFS group experienced a non-significant increase of 1.4% from baseline measures. The 48 h and 72 h ME/CFS groups both experienced non-significant improvements in crPWV (0.56 ms−1 and 1.55 ms−1, respectively).

Conclusions: The findings suggest that those with ME/CFS may not experience exercise-induced vasodilation due to chronic vascular damage, which may be a contributor to the onset of post-exertional malaise (PEM).

Source: Bond J, Nielsen T, Hodges L. Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. International Journal of Environmental Research and Public Health. 2021; 18(5):2366. https://doi.org/10.3390/ijerph18052366 https://www.mdpi.com/1660-4601/18/5/2366/htm (Full text)

Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction. This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year.

Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index. Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary. The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer.

Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter. A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features. These findings suggest that circadian regulation and skin vasodilator responses may play a role in CFS/ME.

Source: Cambras T, Castro-Marrero J, Zaragoza MC, Díez-Noguera A, Alegre J. Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. PLoS One. 2018 Jun 6;13(6):e0198106. doi: 10.1371/journal.pone.0198106. eCollection 2018.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991397/  (Full article)

Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome

Abstract:

The aetiology of chronic fatigue syndrome (CFS) remains controversial and a number of hypotheses have been put forward to explain it. Research into the condition is hindered by the considerable heterogeneity seen across patients but several reports have highlighted disturbances to cholinergic mechanisms in terms of central nervous system activity, neuromuscular function and autoantibodies to muscarinic cholinergic receptors. This paper examines an altogether separate function for acetylcholine and that is its role as an important and generalized vasodilator.

Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients. There are several mechanisms that might lead to ACh endothelial sensitivity in CFS patients and various experiments have been designed to unravel the enigma. These are reported here.

 

Source: Spence VA, Khan F, Kennedy G, Abbot NC, Belch JJ. Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids. 2004 Apr;70(4):403-7. http://www.ncbi.nlm.nih.gov/pubmed/15041034

 

Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome

Abstract:

Although the aetiology of chronic fatigue syndrome (CFS) is unknown, there have been a number of reports of blood flow abnormalities within the cerebral circulation and systemic blood pressure defects manifesting as orthostatic intolerance. Neither of these phenomena has been explained adequately, but recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism.

Our group has previously reported enhanced skin vasodilatation in response to cumulative doses of transdermally applied acetylcholine (ACh), implying an alteration of peripheral cholinergic function. To investigate this further, we studied the time course of ACh-induced vasodilatation following a single dose of ACh in 30 patients with CFS and 30 age- and gender-matched healthy control subjects.

No differences in peak blood flow was seen between patients and controls, but the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects. The time taken to decay to 75% of the peak response in patients and controls was 13.7 +/- 11.3 versus 8.9 +/- 3.7 min (P = 0.03), respectively, and time taken to decay to 50% of the peak response was 24.5 +/- 18.8 versus 15.1 +/- 8.9 min (P = 0.03), respectively.

Prolongation of ACh-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.

 

Source: Khan F, Spence V, Kennedy G, Belch JJ. Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome. Clin Physiol Funct Imaging. 2003 Sep;23(5):282-5. http://www.ncbi.nlm.nih.gov/pubmed/12950326