Resting oxygen consumption and in vivo ADP are increased in myopathy due to complex I deficiency

BACKGROUND: Patients with isolated complex I deficiency (CID) in skeletal muscle mitochondria often present with exercise intolerance as their major clinical symptom. OBJECTIVE: To study the in vivo bioenergetics in patients with complex I deficiency in skeletal muscle mitochondria. METHODS: In vivo bioenergetics were studied in three of these patients by measuring oxygen uptake at rest and during maximal exercise, together with forearm ADP concentrations ([ADP]) at rest. Whole-body oxygen consumption at rest (VO(2)) was measured with respiratory calorimetry. Maximal oxygen uptake (VO(2)max) was measured during maximal exercise on a cycle ergometer. Resting [ADP] was estimated from in vivo (31)P MRS measurements of inorganic phosphate, phosphocreatine, and ATP content of forearm muscle. RESULTS: Resting VO(2) was significantly increased in all three patients: 128 +/- 14% (SD) of values in healthy control subjects. VO(2)max in patients was on average 2.8 times their VO(2) at rest and was only 28% of VO(2)max in control subjects. Resting [ADP] in forearm muscle was significantly increased compared with healthy control subjects (patients 26 +/- 2 microM, healthy controls 9 +/- 2 microM). CONCLUSION: In patients with CID, the increased whole-body oxygen consumption rate at rest reflects increased electron transport through the respiratory chain, driven by a decreased phosphorylation potential. The increased electron transport rate may compensate for the decreased efficiency of oxidative phosphorylation (phosphorylation potential).     

Progressive fat replacement of muscle contributes to the disease mechanism of patients with single,large-scale deletions of mitochondrial DNA

Muscle dysfunction in mitochondrial myopathy is predominantly caused by insufficient generation of energy. We hypothesise that structural changes in muscles could also contribute to their pathophysiology. The aims of this study were to determine fat fractions and strength in selected muscles in patients with chronic progressive external ophthalmoplegia (CPEO), and compare progression of muscle fat fraction with age in individuals with CPEO vs. healthy controls and patients with the m.3243A>G mutation of mitochondrial DNA (mtDNA). Seventeen patients with CPEO and single large-scale deletions of mtDNA, 52 healthy controls, and 12 patients carrying the m.3243A>G mtDNA mutation were included. Muscle fat fractions were measured from cross-sections of paraspinal and leg muscles. Peak muscle strength was assessed from a static dynamometer. There was a direct correlation between age and fat fraction in all muscle groups in CPEO patients and healthy controls (p < 0.05). Analysis of covariance showed a higher progression rate of fat replacement in CPEO patients vs. healthy controls in studied muscle groups (p < 0.05). Patients with the m.3243A>G mutation had slower progression rates of fat replacement. Muscle strength decreased with increasing muscular fat fraction in CPEO patients, no correlation was seen in other groups. This indicates that structural muscle changes contribute to the phenotype of older patients affected by CPEO and large-scale deletions. It should therefore be considered, along with known energy deficiencies, as the cause of exercise intolerance.     

The acute antipanic activity of aerobic exercise

OBJECTIVE: Regular physical activity is anxiolytic for both healthy subjects and patients with panic disorder. However, the acute antipanic activity of exercise has not yet been studied systematically. METHOD: The effects of quiet rest or aerobic treadmill exercise (30 minutes at 70% of maximum oxygen consumption) on cholecystokinin tetrapeptide (CCK-4)-induced panic attacks were studied in a crossover design in 15 healthy subjects. The effects were measured with the Acute Panic Inventory. RESULTS: Panic attacks occurred in 12 subjects after rest but in only six subjects after exercise. In both conditions, CCK-4 administration was followed by a significant increase in Acute Panic Inventory scores; however, prior exercise resulted in significantly lower scores than quiet rest. CONCLUSIONS: Aerobic exercise has an acute antipanic activity in healthy subjects. If the authors' results are confirmed in patients, the optimum intensity and duration of acute exercise for achieving antipanic effects will have to be characterized.     

Die Spiroergometrie in der Diagnostik mitochondrialer Erkrankungen

Cardiopulmonary exercise testing (CPX) is a non-invasive method of recording quantitative data from gas exchange and ventilation for the evaluation of oxidative metabolism at rest and during exercise. Determination of oxygen uptake (VO2) and carbon dioxide output (VCO2) describes the activity of anaerobic vs aerobic metabolism. An incremental exercise test measuring gas exchange, ventilation and lactate release was performed in healthy volunteers and in patients suffering from mitochondrial disorders. At rest as well as during exercise patients with mitochondrial disorders differ from healthy subjects with regard to gas exchange and ventilation parameters. During exercise, the decreased oxygen utilization of skeletal muscle and early activation of anaerobic metabolism in these patients are mirrored by a reduced anaerobic threshold, reduced maximal oxygen uptake and reduced oxygen pulse. Our study shows that CPX is a sensitive and practical clinical screening method of investigating mitochondrial disorders.     

Hemoglobin oxygen saturation as a marker of cerebral hemodynamics in carotid artery occlusion

Cerebral hemodynamics play a pivotal role in stroke pathogenesis. Transcranial Doppler (TCD) studies demonstrated the importance of cerebral vasomotor reactivity (VMR) on the outcome of carotid artery occlusion (CAO). So far, positron emission tomography represents the best technique for detecting both hemodynamic and metabolic aspects of cerebral perfusion adaptive processes in cerebrovascular patients. Near-infrared spectroscopy (NIRS) is a new method allowing for a non-invasive assessment of cerebral blood flow and hemoglobin (Hb) oxygenation parameters.A recent TCD and NIRS study demonstrated that patients with symptomatic CAO had lower VMR values measured by TCD and lower oxygen saturation (oxygen%) increases detected by NIRS than asymptomatic ones. The parameters were obtained simultaneously after CO(2) inhalation. The present study aims to investigate if Hb oxygen % could represent also at rest a marker of hemodynamic status in carotid disease.Thirty-five symptomatic and 17 asymptomatic patients with CAO underwent a simultaneous examination by means of TCD and NIRS at rest condition and during CO(2) reactivity test.Symptomatic patients presented with oxygen% values at rest higher (p = 0.001) and VMR values lower (p < 0.001) than asymptomatic subjects. According to a logistic model, for each unitary VMR increase, the odds of being symptomatic decreases of about 10% (OR = 0.9, p = 0.001); for each unitary increase of oxygen% at baseline, this odd increases of about 23% (OR = 1.23, p = 0.031).In addition to TCD VMR values, oxygen hemoglobin saturation at rest detected by NIRS can discriminate symptomatic from asymptomatic patients with CAO. NIRS can add an important contribution to explain pathophysiological mechanisms of stroke occurrence.     

Acute hypoxemia does not increase blood fibrinolytic activity in man

The influence of acute hypoxemia on blood fibrinolytic activity was investigated in 12 healthy males. Physiologically significant hypoxemia was produced by inspiration of 13% oxygen for 30 min. Six healthy males were exposed to hypoxemia at rest and 6 males to hypoxemia during exhaustive physical exercise on an ergocyclometer. During control experiments both groups of health males inspired 21% oxygen. In 5 patients with manifest respiratory insufficiency the effect of hypoxemia at rest was studied during withdrawal of oxygen treatment for up to 2.5 hours. No increase in fibrinolytic activity (measured with euglobulin clot lysis and fibrin plates) due to hypoxemia was observed either in resting healthy males or in patients. In healthy males the increase in fibrinolytic activity after physical exercise at 13% oxygen was even somewhat lower compared to 21% oxygen. No changes in other hemostatic parameters (activated partial thromboplastin time, factor VIII-related antigen, fibrinogen, plasminogen, alpha-2-antiplasmin, fibrin(ogen) degradation products) that could be attributed to hypoxemia, were observed in any group tested. It was concluded that short-term acute hypoxemia does not increase blood fibrinolytic activity in man.     

Residual muscle cytochrome c oxidase activity accounts for submaximal exercise lactate threshold in chronic progressive external ophthalmoplegia

The data from histological, biochemical, and mitochondrial DNA (mtDNA) studies of muscle biopsies from 10 patients affected with chronic progressive external ophthalmoplegia (CPEO) were related to dynamic and metabolic parameters of incremental submaximal exercise. Maximum power output was reduced in all patients as compared to controls. Analysis of the venous lactate curve during exercise revealed a lactate threshold at exercise levels ranging from 40 to 50% of the predicted maximal power output. An earlier significant increase in lactate could be detected by calculating the mean δ lactate. Lactate values were inversely correlated with the cytochrome c oxidase (COX) activity of isolated muscle mitochondria. No relationship was found between lactate values and the number of ragged red fibers, or cytochrome c oxidase-negative fibers or the proportion of deleted mtDNA measured in muscle biopsy specimens. The discussion underscores the value of lactate kinetics in assessing skeletal muscle function, as well as the use of muscle COX levels to predict the effectiveness of wild-type complementation of deleted skeletal muscle mtDNA in in vivo contractile performance of CPEO subjects. © 1996 John Wiley & Sons, Inc.     

Functional principal component analysis of H-reflex recruitment curves

We examined how cerebral blood flow velocity (CBV) and neurovascular coupling is influenced by exercise. Blood velocities in the posterior and middle cerebral arteries (PCAv and MCAv) during rest and cycling exercise at 60% estimated maximal oxygen consumption were measured. Neurovascular coupling was quantified as the ΔPCAv with visual stimulation. During exercise, despite a 15.2±13.6% and 26.1±22.5% increase from rest in the MCAv and PCAv, respectively, neurovascular coupling was unaltered. Thus, despite regionally heterogeneous elevations in CBV during exercise, neurometabolic coupling is maintained.     

Unique cardiopulmonary exercise test responses in overweight middle-aged adults with obstructive sleep apnea

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive nighttime obstructions of the upper airway that induce hypoxemia, hypercapnia, sympathetic activation, and arousals. This disorder induces cardiovascular autonomic imbalance and contributes to the development of hypertension. While the diagnostic and prognostic utility of exercise testing is well established in cardiology, the clinical utility of the exercise test in screening for OSA has not been carefully explored. To explore this potential application, we contrasted cardiopulmonary responses to exercise testing in patients recently diagnosed with OSA with apparently healthy counterparts of similar physical inactivity history, age, and body habitus. METHODS: Twenty-three normotensive overweight adults with OSA [apnea-hypopnea index (AHI)=24.7+/-13.5 events h(-1); body mass index (BMI)=33.1+/-5.5 kg m(-2); age=45.6+/-10.7 years] and nine apparently healthy controls of similar age and morphology (BMI=29.5+/-5.5 kg m(-2); age=40.2+/-8.1 years; AHI=4.9+/-0.1) completed a maximal ramping cardiopulmonary exercise tolerance test on a cycle ergometer. Measures included oxygen consumption (VO(2)pk), ventilation (V(E)), heart rate (HR), blood pressure (BP), cardiac output (Qc), and stroke volume (SV). RESULTS: Age, BMI, rest HR, rest BP, rest and exercise cardiac index (QI), rest and exercise stroke volume index (SVI), and V O(2)pk were not different between OSA patients and controls (p>0.05). Exercise heart rate was significantly lower and diastolic BP higher in the OSA group (p<0.05). In the physically active recovery (low-load pedaling), systolic BP recovery was delayed (p<0.05) in the OSA group while diastolic BP tended to remain higher (p=0.056). CONCLUSION: Patients with OSA have a distinctive response to graded exercise, characterized by a blunted HR response, markedly delayed systolic BP response in early recovery, and elevated diastolic BP in both exercise and early recovery. Clinical trials are justified to determine the clinical utility of graded exercise testing to independently inform clinical decision-making for triaging patients to diagnostic polysomnography.     

Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome

The purpose of this study was to determine if patients with the chronic fatigue syndrome have less vagal power during walking and rest periods following walking, in comparison to a group of healthy controls. Eleven patients (ten women and one man) who fulfilled the case definition for chronic fatigue syndrome modified to reduce heterogeneity and eleven healthy, but sedentary, age- and sex-matched controls walked on a treadmill at 2.5 mph four times each for 4 min duration. Between each period of walking, subjects were given a 4-min seated rest period. Vagal power, a Fourier-based measure of cardiac, parasympathetic activity in the frequency range of 0.15 to 1.0 Hz, was computed. In each period of walking and in one period of rest, patients had significantly less vagal power than the control subjects despite there being no significant group-wise differences in mean heart rate, tidal volume, minute volume, respiratory rate, oxygen consumption or total spectrum power. Further, patients had a significant decline in resting vagal power after periods of walking. These results suggest a subtle abnormality in vagal activity to the heart in patients with the chronic fatigue syndrome and may explain, in part, their post-exertional symptom exacerbation.     

Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude.

The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level. Global cerebral blood flow at rest and during exercise on a bicycle ergometer was measured by the Kety-Schmidt technique. Cerebral metabolic rates of oxygen, glucose, and lactate were calculated by the Fick principle. Cerebral function was assessed by a computer-based measurement of reaction time. At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow and oxidative metabolism are unaltered after high-altitude acclimatization from sea level, despite marked changes in breathing and other organ functions.     

Cortical activation during two verbal fluency tasks in schizophrenic patients and healthy controls as assessed by multi-channel near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is an optical imaging method that allows non-invasive in-vivo measurements of changes in the concentration of oxygenated (O(2)Hb) and deoxygenated (HHb) hemoglobin in brain tissue. For the present study, we examined 12 schizophrenic patients and 12 age- and gender-matched healthy controls by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of two versions of the Verbal Fluency Test (VFT; letter and category version). The results indicate that the verbal fluency tasks generally led to clear frontal activation in healthy controls, which was significantly reduced in schizophrenic patients. The letter version of the VFT induced overall stronger activation than the category version, the group difference being particularly pronounced for phonological fluency. Moreover, significant positive correlations between task-related activation effects in prefrontal and temporal NIRS channels were found in both schizophrenic patients and healthy controls. The results confirm functional deficits within the frontal lobe in patients suffering from schizophrenic illnesses, but do not confirm previous findings on abnormal fronto-temporal correlations or increased temporal activation in this group of patients. The data furthermore underline the usefulness of functional NIRS in monitoring hemodynamic responses associated with cognitive processes in healthy controls and patients with neuro-psychiatric disorders.     

Multi-channel near-infrared spectroscopy shows reduced activation in the prefrontal cortex during facial expression processing in pervasive developmental disorder

Aim: The purpose of the present study was to investigate whether individuals with pervasive developmental disorders (PDD) show differential activation during an emotional activation task compared with age‐ and sex‐matched controls, by measuring changes in the concentration of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin, using near‐infrared spectroscopy (NIRS). Methods: Fourteen patients with PDD and 14 age‐ and sex‐matched healthy controls participated in the study. The relative changes of concentrations of oxyHb and deoxyHb were measured on NIRS during an implicit processing task of fearful expression using Japanese standard faces. Results: PDD patients had significantly reduced oxyHb changes in the prefrontal cortex (PFC) compared to healthy controls. Conclusion: PFC dysfunction may exist in PDD.     

Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy

The purpose of this study was to investigate the correlation between the level of mutated mitochondrial DNA in muscle and oxidative capacity in 24 patients with mitochondrial myopathy (MM). Maximal oxygen uptake (VO(2max)), workload (W(max)), and venous plasma lactate levels were measured during an incremental cycle test to exhaustion in 17 patients with point mutations of mtDNA and in seven with single, large-scale deletions of mtDNA (chronic progressive external ophthalmoplegia [CPEO]). Results were compared with those in 25 healthy matched subjects. The mutation load in MM patients was 67 +/- 5% (range, 29 - 99%). VO(2max) and W(max) correlated with percentage of heteroplasmy (r > 0.82; p < 0.005) and were lower in patients versus healthy subjects (p < 0.000005). Exercise-induced peak increases in heart rate, ventilation, and resting plasma lactate levels correlated with muscle mutation load (r > 0.71; p < 0.005). Exercise-induced increases in plasma lactate correlated with muscle mutation load in CPEO patients (r = 0.95; p < 0.005). Impaired oxidative capacity and ragged red muscle fibers were found in CPEO and 3243A-->G patients with mutation loads as low as 45 and 57%, respectively. The study indicates that oxidative capacity correlates directly with skeletal muscle mutation load in MM patients, and that the mutation threshold level for impaired oxidative metabolism in MM patients is lower than found in in vitro studies.     

Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy.

A cardinal feature of impaired skeletal muscle oxidative metabolism in mitochondrial myopathies is a limited ability to increase the extraction of O(2) from blood relative to the increase in O(2) delivery by the circulation during exercise. We investigated whether aerobic forearm exercise would result in an abnormal increase in venous effluent O(2) in patients with impaired skeletal muscle oxidative phosphorylation attributable to mitochondrial disease. We monitored the partial pressure of O(2) (PO(2)) in cubital venous blood at rest, during handgrip exercise, and during recovery in 13 patients with mitochondrial myopathy and exercise intolerance and in 13 healthy control and 11 patient control subjects. Resting and recovery venous effluent PO(2) were similar in all subjects, but during exercise venous PO(2) paradoxically rose in mitochondrial myopathy patients from 27.2 +/- 4.0mmHg to 38.2 +/- 13.3mmHg, whereas PO(2) fell from 27.2 +/- 4.2mmHg to 24.2 +/- 2.7mmHg in healthy subjects and from 27.4 +/- 9.5mmHg to 22.2 +/- 5.2mmHg in patient controls. The range of elevated venous PO(2) during forearm exercise in mitochondrial myopathy patients (32 to 82mmHg) correlated closely with the severity of oxidative impairment as assessed during cycle exercise. We conclude that measurement of venous PO(2) during aerobic forearm exercise provides an easily performed screening test that sensitively detects impaired O(2) use and accurately assesses the severity of oxidative impairment in patients with mitochondrial myopathy and exercise intolerance.     

Examination of NIRS for evaluation of frontal lobe function in diffuse axonal injury (DAI) patients]

The purpose of this study is to compare diffuse axonal injury (DAI) patients with healthy controls by using near infrared spectroscopy (NIRS). The Wisconsin Card Sorting Test Keio Version (KWCST), a standard task paradigm to detect human frontal lobe dysfunction was set as a method. The result of the examination showed that compared with DAI patients, wider increase of total hemoglobin was admitted in the frontal part of the brain of healthy people during the KWCST. This suggests that NIRS would serve as an objective indicator to evaluate the frontal lobe function in DAI patients.     

Reduced frontal functional asymmetry in schizophrenia during a cued continuous performance test assessed with near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) allows noninvasive, in vivo measurement of changes in the concentrations of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) in brain tissue based on their distinctive optical properties. A previous NIRS investigation on healthy subjects (Fallgatter and Strik 1997) found indications of right frontal activation during a Continuous Performance Test (CPT) that are consistent with results from positron emission tomography (PET) and event-related potentials studies. The indications consisted of right frontal blood oxygenation changes, consistent with a hemodynamic response, along with a significant left frontal increase in HHb. The current study investigated whether this characteristic lateralized frontal NIRS activation pattern was present in a group of nine schizophrenia patients during the execution of a CPT. In contrast to the previous study, no overall or hemispheric activation effects were found in the schizophrenia subjects. Direct comparison of the results of the two studies confirmed group differences, with a lack of lateralized activation in schizophrenia patients. Furthermore, a trend of higher left/right HHb ratios at rest and during activation was found in patients with schizophrenia. The finding is interpreted as a sign of reduced specific lateralized frontal reactivity, possibly based on a left hemisphere functional deficit.     

Strength and physiological response to exercise in patients with chronic fatigue syndrome

OBJECTIVE: To measure strength, aerobic exercise capacity and efficiency, and functional incapacity in patients with chronic fatigue syndrome (CFS) who do not have a current psychiatric disorder. METHODS: Sixty six patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder were recruited into the study. Exercise capacity and efficiency were assessed by monitoring peak and submaximal oxygen uptake, heart rate, blood lactate, duration of exercise, and perceived exertion during a treadmill walking test. Strength was measured using twitch interpolated voluntary isometric quadriceps contractions. Symptomatic measures included physical and mental fatigue, mood, sleep, somatic amplification, and functional incapacity. RESULTS: Compared with sedentary controls, patients with CFS were physically weaker, had a significantly reduced exercise capacity, and perceived greater effort during exercise, but were equally unfit. Compared with depressed controls, patients with CFS had significantly higher submaximal oxygen uptakes during exercise, were weaker, and perceived greater physical fatigue and incapacity. Multiple regression models suggested that exercise incapacity in CFS was related to quadriceps muscle weakness, increased cardiovascular response to exercise, and body mass index. The best model of the increased exercise capacity found after graded exercise therapy consisted of a reduction in submaximal heart rate response to exercise. CONCLUSIONS: Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function.     

THE EFFECT OF PHYSICAL CONDITIONING SUGGESTS ADAPTATION IN PROCOAGULANT AND FIBRINOLYTIC POTENTIAL

Acute exercise evokes a transient increase in procoagulant activity. We evaluated the effect of physical conditioning on the activation of the coagulation and fibrinolytic systems. Two groups of subjects of different aerobic endurance levels (athletes and controls with maximal oxygen uptake (VO_{2 max}) 68,4 and 52,6 ml·kg⁻¹·min⁻¹, respectively), were tested at rest and after standardized exercise at 80 % of their individual VO_{2 max}. There was a significant increase in prothrombinfragment 1+2 (F1+2) level among controls in response to standardized exercise (p<0.05), whereas no significant difference in the level of F1+2 between athletes and controls at rest or in response to exercise was demonstrated. Tissue plasminogen activator (tPA) antigen level at rest was significantly lower in athletes compared to controls (p<0.03). A significant increase was found in the tPA level after standardized exercise in both groups (p<0.02), which was lower in athletes compared to controls (p<0.05). There were no significant differences between athletes and controls in plasminogen activator inhibitor-1 (PAI-1) and thrombin antithrombin complex (TAT) levels at rest. Athletes had a significantly lower PAI-1 level than controls after exercise (p<0.05). In conclusion, the present study suggests an increased activation of the coagulation system in response to exercise in controls only. It also suggests adaptive changes in fibrinolytic potential induced by physical conditioning, as demonstrated by the lower level of tPA at rest and the lower levels of tPA and PAI-1 after exercise in athletes compared to controls. © 1997 Elsevier Science Ltd     

Effects of exercise induced oxidative stress on glutathione levels in Parkinson’s disease on and off medication

Resting plasma glutathione (GSH) levels are lower in individuals with Parkinson’s disease (PD) than any other neurological condition. Medications used to treat PD have also been shown to further decrease this depletion. Acute exercise has been shown to be an effective tool to produce oxidative stress in other populations as reflected in lowering levels of GSH. The purpose of this study was to determine how PD responds to acute exercise stress and how medication affects these responses. Fourteen men with PD and 14 men without PD underwent an exercise stress test. Subjects with PD performed the test once off PD medication (PD-Off-med) for 12 h then again 1 week later on PD medication (PD-On-med). GSH and glutathione disulfide (GSSG), were collected via blood draws at rest and after peak exercise along with peak VO₂. At rest and at peak exercise GSH levels and the GSH:GSSG ratio were significantly lower in the PD-On-med and PD-Off-med as compared to controls. GSSG levels were significantly higher in both medication conditions at rest and peak exercise compared to controls. When comparing PD-On-med vs. PD-Off-med at rest and peak exercise, the PD-On-med had lower GSH levels, a lower GSH:GSSG ratio and higher GSSG levels. VO₂ correlated positively with GSH levels. Subjects with PD have lower plasma GSH levels than healthy controls at rest and at peak exercise.