De inspanningskapaciteit van (een deel van de) CVS-patiënten (de "konditie"),
gemeten naar zuurstofopname (VO2max), verzuringsdrempel en maximale inspanning,
is beduidend lager dan die van inaktieve "gezonde" proefpersonen en
neemt die daarbovenop ook nog (sterk) af bij een tweede inspanningstest,
zoals ook al eerder vastgesteld werd in een studie van VanNess en Stevens.
Hierbij moet worden aangetekend dat het onderzoek een relatief kleine groep "CVS"-patiënten betreft
die ziek geworden zijn na een infektie (sudden onset-ME/CVS of "postviraal ME/CVS").
Het zou goed zijn om dubbele fietstest-studies te herhalen op grote schaal, waarbij sub-
groepen op basis van objektieve markers (bijv. NK cel-aktiviteit) met elkaar vergeleken worden.
De auteurs hebben onderzocht in hoeverre de
aerobe ATP-produktie van
mitochondria afwijkt.
Daartoe maten zij de
citraatsynthase-aktviteit, betrokken bij de eerste stap van de
citroen-zuurcyclus, en de
ATP-produktie
via complex I en II van de oxidatieve fosfopylering.
Omdat zij hier geen afwijkingen vonden,
konkluderen zij dat het probleem veroorzaakt wordt door bloedtoevoer (aanvoer van grondstof)
en níet door de ATP-produktie en de mitochondria: de fabrieken (zoals o.m. door Myhill gesteld).
Gezien het feit dat men onder meer complex III tot en met V niet onderzocht zijn
en bijvoorbeeld excessieve hoeveelheden stikstofoxide en
waterstofdisulfide (H2S)
in staat lijken om complex III (en dus de ATP-produktie door mitochondria) ernstig te verstoren
lijkt me deze verstrekkende konklusie niet echt gerechtvaardigd door de bevindingen.
Enkele relevante citaten uit het studierapport:
Chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) as a syndrome
was defined in consensus meetings by Fukuda et al [1].
Patients who visited the CFS/ME Clinic Amsterdam and healthy sedentary controls
were invited for the study.
All patients fulfilled the criteria of Fukuda et al [1] for CFS/ME
and reported the start of symptoms after an infectious disease.
Inclusion of patients for the study started in May 2007 and the last CPET was in December 2007.
At screening 8 of the 23 patients fulfilled exclusion criteria for the study.
Exhaustion of the leg muscles was the limiting symptom in all participants.
[Tabel 2: Prestaties patiënten en "gezonde" proefpersonen bij fietstest (CPET) 1 en 2]
[Tabel 3: Verschillen tussen prestatie fietstest 1 en 2 bij patienten en "gezonde" proefpersonen]
[De met rood aangegeven cijfers lijken me niet juist berekend]
The improvement in the performance of the controls is likely due to the effect of training.
In the group of patients the performance is the result of a similar training effect
which is counteracted by the effect of the postexertional malaise.
Based on the oxygen uptake test,
the patients not only performed worse than controls in the first test,
but the recovery after 24h was not completed in this group as well.
The lower VO2 at the anaerobic threshold indicated that
the difference in VO2 at maximal work rate
was not due to a reduced willingness to perform in the CFS/ME group.
The ATP synthesis assayed via the reduction of complex I, expressed on basis of protein
were similar in the groups,
and also when the ATP synthesis rate was expressed on basis of citrate synthase.
The same was found for ATP synthesis via complex II.
Two possible explanations for the insufficient energy production in CFS remained:
- a lower transport capacity of oxygen as in anemia or
- a mitochondrial insufficiency.
We showed that the mitochondrial ATP production shows no defect.
Then
the conclusion must be that the transport capacity of oxygen is limited in CFS patients.
The results of the present study .. demonstrated that
the oxidative phosphorylation in PCMB [moet zijn: PBMC, FT] of CFS/ME patients is fully normal.
Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study
despite a normal oxidative phosphorylation capacity.
Journal of Translational Medicine2010, 8:93. doi:10.1186/1479-5876-8-93
Vermeulen RCW, Kurk RM, Visser FC, Sluiter W, Scholte HR.
Abstract
Background:
The aim of this study was to investigate
the possibility that
a decreased mitochondrial ATP synthesis
causes muscular and mental fatigue and
plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).
Methods:
Female patients (n=15) and controls (n=15)
performed a cardiopulmonary exercise test (CPET) by cycling at
a continuously increased work rate till maximal exertion.
The CPET was repeated 24 h later.
Before the tests,
blood was taken for the isolation of peripheral blood mononuclear cells (PBMC),
which were processed in a special way to preserve their oxidative phosphorylation,
which was tested later
in the presence of ADP and phosphate in permeabilized cells
with glutamate, malate and malonate plus or minus the complex I inhibitor rotenone, and
succinate with rotenone plus or minus the complex II inhibitor malonate
in order to measure
the ATP production via Complex I and II, respectively.
Plasma CK was determined as
a surrogate measure of a decreased oxidative phosphorylation in muscle,
since the previous finding
that in a group of patients with external ophthalmoplegia
the oxygen consumption by isolated muscle mitochondria
correlated negatively with plasma creatine kinase, 24 h after exercise.
Results:
At both exercise tests
the patients reached
the anaerobic threshold and the maximal exercise
at a much lower oxygen consumption
than the controls and
this worsened in the second test.
This implies
an increase of lactate,
the product of anaerobic glycolysis, and
a decrease of the mitochondrial ATP production
in the patients.
In the past
this was also found
in patients with defects in the mitochondrial oxidative phosphorylation.
However
the oxidative phosphorylation in PBMC
was similar in CFS/ME patients and controls.
The plasma creatine kinase levels
before and 24 h after exercise
were low in patients and controls,
suggesting normality of the muscular mitochondrial oxidative phosphorylation.
Conclusion:
The decrease in mitochondrial ATP synthesis in the CFS/ME patients
is not caused by
a defect in the enzyme complexes catalyzing oxidative phosphorylation,
but in another factor.
http://www.translational-medicine.com/content/pdf/1479-5876-8-93.pdf
Met dank aan Rob
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