Impaired oxygen extraction in metabolic myopathies: Detection and quantification by near‐infrared spectroscopy

Grassi, Bruno; Marzorati, Mauro; Lanfranconi, Francesca; Ferri, Alessandra; Longaretti, Miriam; Stucchi, Andrea; Vago, Paola; Marconi, C.; Morandi, Lucia

doi:10.1002/mus.20708

Cited by 97 publications

(95 citation statements)

References 33 publications

(100 reference statements)

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“…Our previous studies indicate that mitochondrial defects in skeletal muscle dramatically disrupt this relationship (21,22,51,53). During exercise in mitochondrial myopathies, oxygen utilization is blocked as indicated by low peak systemic a-vO 2 difference and high oxygen levels in active muscle (19). At the same time, oxygen transport is exaggerated (indicated by high cardiac output relative to workload and V O 2 ) with the most severe mismatches in O 2 delivery relative to utilization found in the most severe mitochondrial defects (51).…”

Section: Discussionmentioning

confidence: 99%

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Heinicke

Taivassalo

Wyrick

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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-Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low V O2peak (28 Ϯ 9% of predicted) and exaggerated systemic O 2 delivery relative to O2 utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high V E/V O2peak, (MM ϭ 104 Ϯ 18; C ϭ 42 Ϯ 8, P Յ 0.001), and V E/V CO2peak, (MM ϭ 54 Ϯ 9; C ϭ 34 Ϯ 7, P Յ 0.01); a steeper slope of increase in ⌬V E/⌬V CO2 (MM ϭ 50.0 Ϯ 6.9; C ϭ 32.2 Ϯ 6.6, P Յ 0.01); and elevated peak respiratory exchange ratio (RER), (MM ϭ 1.95 Ϯ 0.31, C ϭ 1.25 Ϯ 0.03, P Յ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower Pa CO 2 and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated V E/V O2, V E/V CO2, and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.hyperventilation; lactic acidosis; metaboreflex; exercise; oxidative phosphorylation EXERTIONAL DYSPNEA WAS FIRST described as a symptom that limited exercise in mitochondrial myopathy (MM) in patients with a familial disorder studied by Linderholm and coworkers in the 1960s (36, 38), a disease now recognized to be attributable to a mutation in the iron-sulfur cluster scaffold (ISCU) gene (40, 42) and associated with deficiency of multiple iron-sulfur proteins, including succinate dehydrogenase and aconitase (20,21). Exertional dyspnea has since been described as a dominant feature of exercise intolerance in other mitochondrial myopathies that severely restrict muscle oxidative phosphorylation (3a, 22). Moreover, mitochondrial disease has been suggested to be an underrecognized cause of unexplained exertional dyspnea (16,25), although, these reports lacked genetic confirmation and, in most cases, did not include biochemical assessment to indicate the presence and severity of the putative mitochondrial defect (16). To better define the physiological manifestations of exertional dyspnea in mitochondrial myopathy, we have evalu...

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Section: Discussionmentioning

confidence: 99%

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Heinicke

Taivassalo

Wyrick

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Differently from the size of the O 2 deficit at the same relative work rate (see above), this variable ([PCr] decrease at the same absolute work rate) seems nicely correlated with exercise tolerance, as estimated on the basis of _ VO 2 peak data (Fig. 3): excellent ATHL, good in CTRL, poor in HTR and MM, very poor in McA (Lanfranconi et al 2006;Grassi et al 2007Grassi et al , 2009). The curve shown in Fig.…”

Section: Introductionmentioning

confidence: 88%

“…6 in di Prampero 1981). This assumption does not apply to McA, in whom the myophosphorylase deficiency determines a substantially complete glycolytic impairment (see Grassi et al 2007).…”

Section: Introductionmentioning

confidence: 97%

Slow $$ \dot{V}{\text{O}}_{2} $$ kinetics during moderate-intensity exercise as markers of lower metabolic stability and lower exercise tolerance

et al. 2010

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An analysis of previously published data obtained by our group on patients characterized by markedly slower pulmonary VO₂ kinetics (heart transplant recipients, patients with mitochondrial myopathies, patients with McArdle disease) was carried out in order to suggest that slow VO₂ kinetics should not be considered the direct cause, but rather a marker, of impaired exercise tolerance. For a given ATP turnover rate, faster (or slower) VO₂ kinetics are associated with smaller (or greater) muscle [PCr] decreases. The latter, however, should not be taken per se responsible for the higher (or lower) exercise tolerance, but should be considered within the general concept of "metabolic stability". Good muscle metabolic stability at a given ATP turnover rate (~power output) is associated with relatively smaller decreases, compared to rest, in [PCr] and in the Gibbs free energy of ATP hydrolysis, as well as with relatively smaller increases in [Pi], [ADP(free)], [AMP(free)], and [IMP(free)], metabolites directly related to fatigue. Disturbances in muscle metabolic stability can affect muscle function in various ways, whereas good metabolic stability is associated with less fatigue and higher exercise tolerance. Smaller [PCr] decreases, however, are strictly associated with a faster VO₂ kinetics. Thus, faster VO₂ kinetics may simply be an "epiphenomenon" of a relatively higher metabolic stability, which would then represent the relevant variable in terms of fatigue and exercise tolerance.

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“…In response to ischemia, it also allows evaluation of dynamic changes in microcirculation. Using NIRS, the changes in skeletal muscle oxygenation have been demonstrated in chronic heart failure patients at rest and during exercise [20,29], in patients undergoing haemodialysis [21], during abdominal aortic and cardiac surgery [30,31], and in patients with peripheral arterial disease [32], cirrhosis [33], septic shock [22,23], and metabolic myopathies [34]. NIRS has been already applied to demonstrate the effect of IPC on changes in myocardial oxygenation in dogs; IPC has been induced by repeated periods of coronary occlusion [35].…”

Section: Discussionmentioning

confidence: 99%

Use of Near Infrared Spectroscopy to Asses Remote Ischemic Preconditioning in Skeletal Muscle

2013

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Remote ischemic preconditioning (IPC) is a procedure during which brief periods of ischemia protect distant organ from ischemiareperfusion injury. Appling IPC on an upper arm, this phenomenon has been demonstrated in several studies. Skeletal muscle tissue oxygenation at rest (StO 2 ) and StO 2 deoxygenation rate during vascular occlusion can be measured using near infrared spectroscopy (NIRS). We aimed to investigate the effects of remote upper arm IPC on StO 2 and flow-mediated dilatation (FMD) in healthy male volunteers. In a randomized controlled crossover trial, resting StO 2 , StO 2 deoxygenation rate, and FMD were measured on testing arm at baseline and after 60 minutes. After basal measurements IPC protocol on a contralateral arm was performed. StO 2 deoxygenation rate was significantly lower after remote, the IPC cycles in comparison to deoxygenation rate at baseline (9.7 ± 2.6 versus 7.5 ± 2.5%, = 0.002). Comparison of deoxygenation rates showed a significant difference between the IPC and the control protocol ( = 5.512, = 0.003). No differences were observed in FMD before and after remote IPC and in the control protocol. In healthy young adults, remote IPC reduces StO 2 deoxygenation rate but has no significant impact on FMD. NIRS technique offers a novel approach to asses skeletal muscle adaptation in response to remote ischemic stimuli.

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Impaired oxygen extraction in metabolic myopathies: Detection and quantification by near‐infrared spectroscopy

Cited by 97 publications

References 33 publications

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Slow $$ \dot{V}{\text{O}}_{2} $$ kinetics during moderate-intensity exercise as markers of lower metabolic stability and lower exercise tolerance

Use of Near Infrared Spectroscopy to Asses Remote Ischemic Preconditioning in Skeletal Muscle

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