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http://www.translational-medicine.com/content/pdf/1479-5876-8-93.pdf
Journal of Translational Medicine
Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity
Ruud CW Vermeulen1, Ruud M Kurk1, Frans C Visser1, Wim Sluiter2 and
Hans R Scholte3
1CFS/ME and Pain Research Center Amsterdam, Waalstraat 25-31, 1078 BR
Amsterdam, The Netherlands.
2Department of Neurology, Erasmus MC University Medical Center,
Rotterdam, The Netherlands.
3Department of Neuroscience, Erasmus MC University Medical Center,
Rotterdam, The Netherlands.
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.
Journal of Translational Medicine
Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity
Ruud CW Vermeulen1, Ruud M Kurk1, Frans C Visser1, Wim Sluiter2 and
Hans R Scholte3
1CFS/ME and Pain Research Center Amsterdam, Waalstraat 25-31, 1078 BR
Amsterdam, The Netherlands.
2Department of Neurology, Erasmus MC University Medical Center,
Rotterdam, The Netherlands.
3Department of Neuroscience, Erasmus MC University Medical Center,
Rotterdam, The Netherlands.
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.