Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

Barbosa, Priscila; Ferreira, Eloara Vieira Machado; Ota-­Arakaki, Jaquelina Sonoe; Takara, Luciana S.; Moura, Juliana de; Nascimento, Rúbia B.; Nery, Luíz Eduardo; Neder, J. Alberto

doi:10.1007/s00421-010-1799-6

Cited by 30 publications

(29 citation statements)

References 53 publications

(100 reference statements)

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“…Li and co-workers (30) previously reported a preferential atrophy of glycolytic fibers in a mouse model of HF, which has also been observed in patients with PAH (33), sepsis (35) and chronic obstructive pulmonary disease (16). Chronic hypoxia (commonly observed in PAH patients (2) and in this model, where arterial O 2 saturation can be less than 80% (27)), however, results in a similar decline in FCSA in all fiber types and not a preferential loss in glycolytic fibers (55), leaving hypoxia per se an unlikely explanation. A more pronounced activation of the ubiquitin-proteasome system and protein breakdown have been suggested to occur in glycolytic compared with oxidative muscle groups (7).…”

Section: H406 Skeletal Muscle Oxygen Flux In Hfmentioning

confidence: 99%

“…However, complex I deactivation (coupled with reductions in oxygen transport and mitochondrial volume density) may provide a profound limitation to energy provision (9), especially under conditions of high ATP demand such as during exercise (2). This mitochondrial dysfunction therefore might, at least in part, underlie the strong relationship between reduction in exercise tolerance and mortality in left and right ventricular heart failure, but also other chronic diseases (6,36).…”

Section: H407mentioning

confidence: 99%

“…A H408 SKELETAL MUSCLE OXYGEN FLUX IN HF reduction in SDH activity, fiber size and capillary density could, in part, explain the lower V O 2max observed in patients with chronic HF (36,43,45), and the poor relation between V O 2max and ejection fraction in these patients (45,51). In addition, a reduction in skeletal muscle mitochondrial volume density would slow the rate at which oxidative phosphorylation rises to meet the energy demands of exercise (V O 2max kinetics (2,41)). These dynamics are expected to be further slowed by the reduced ADP sensitivity of the remaining mitochondria: a greater ADP accumulation being required to obtain a given drive for oxidative phosphorylation in chronic HF muscle.…”

Section: H407mentioning

confidence: 99%

“…Mortality rates of patients with PAH and RV HF are very high: 20 to 40% in the first 3 years after diagnosis (5). PAH and HF are characterized by a reduced tolerance to muscular exercise despite new therapies (2,19,21,33). Interestingly, the reduction in the maximal oxygen uptake (V O 2max ) is a better predictor of mortality than the central hemodynamic deficit or other traditional risk factors (36).…”

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confidence: 99%

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Regional skeletal muscle remodeling and mitochondrial dysfunction in right ventricular heart failure

Wüst¹,

Myers

Stones³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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ance is a cardinal symptom of right ventricular heart failure (RV HF) and skeletal muscle adaptations play a role in this limitation. We determined regional remodeling of muscle structure and mitochondrial function in a rat model of RV HF induced by monocrotaline injection (MCT; 60 mg·kg Ϫ1 ; n ϭ 11). Serial sections of the plantaris were stained for fiber type, succinate dehydrogenase (SDH) activity and capillaries. Mitochondrial function was assessed in permeabilized fibers using respirometry, and isolated complex activity by blue native gel electrophoresis (BN PAGE). All measurements were compared with saline-injected control animals (CON; n ϭ 12). Overall fiber cross-sectional area was smaller in MCT than CON: 1,843 Ϯ 114 vs. 2,322 Ϯ 120 m 2 (P ϭ 0.009). Capillary-to-fiber ratio was lower in MCT in the oxidative plantaris region (1.65 Ϯ 0.09 vs. 1.93 Ϯ 0.07; P ϭ 0.03), but not in the glycolytic region. SDH activity (P ϭ 0.048) and maximal respiratory rate (P ϭ 0.012) were each ϳ15% lower in all fibers in MCT. ADP sensitivity was reduced in both skeletal muscle regions in MCT (P ϭ 0.032), but normalized by rotenone. A 20% lower complex I/IV activity in MCT was confirmed by BN PAGE. MCT-treatment was associated with lower mitochondrial volume density (lower SDH activity), quality (lower complex I activity), and fewer capillaries per fiber area in oxidative skeletal muscle. These features are consistent with structural and functional remodeling of the determinants of oxygen supply potential and utilization that may contribute to exercise intolerance and reduced quality of life in patients with RV HF. bioenergetics; exercise; mitochondrial complex I; respirometry; monocrotaline AN INCREASE IN PULMONARY ARTERIAL pressure increases the loading on the right ventricle of the heart. If sustained, pulmonary arterial hypertension (PAH) results in right ventricular hypertrophy and ultimately to right ventricular heart failure (RV HF), the major cause of death in sufferers of PAH (5, 21). Mortality rates of patients with PAH and RV HF are very high: 20 to 40% in the first 3 years after diagnosis (5). PAH and HF are characterized by a reduced tolerance to muscular exercise despite new therapies (2,19,21,33). Interestingly, the reduction in the maximal oxygen uptake (V O 2max ) is a better predictor of mortality than the central hemodynamic deficit or other traditional risk factors (36). Consequently, correction of the central blood flow limitation by heart transplantation does not consistently resolve functional limitations in patients with HF (43), supporting the view that skeletal muscle remodeling plays an important role in exercise intolerance and mortality in many chronic disease states including PAH and RV HF (17,33,54).A common observation in patients with LV (32) and RV (33) HF is muscle atrophy and weakness, that contributes to a loss of power generating capacity. This may be accompanied by a shift in muscle fiber type expression away from fatigueresistant type I fibers, towards type II (33, 42, 44) and changes i...

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Section: H406 Skeletal Muscle Oxygen Flux In Hfmentioning

confidence: 99%

Section: H407mentioning

confidence: 99%

Section: H407mentioning

confidence: 99%

mentioning

confidence: 99%

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Regional skeletal muscle remodeling and mitochondrial dysfunction in right ventricular heart failure

Wüst¹,

Myers

Stones³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…A computer based literature search of PubMed extending over the last decade generated over 600 hits when combining the terms 'nearinfrared spectroscopy' and 'muscle'. As examples, recent papers include using NIRS experimentally for exercise physiology (Denis et al 2010;Elcadi et al 2011), and clinically as a tool to discriminate between normal and pathological states (Barbosa et al 2011;Cohn et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Reliability of near-infrared spectroscopy for measuring forearm and shoulder oxygenation in healthy males and females

et al. 2011

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This study determined the day-to-day reliability of NIRS-derived oxygenation responses (∆StO(2)%) for isometric contractions and for cuff occlusion. Twenty-four subjects (12 males and 12 females) were tested for 2 days (4-6 days interval). Variables generated were: (1) ∆StO(2)% for isometric contractions (10, 30, 50 and 70% MVC) for descending trapezius (TD) and extensor carpi radialis (ECR) muscles; (2) slope changes in total haemoglobin (HbTslope) and deoxyhaemoglobin (HHbslope) for the ECR using upper arm venous (VO, 50 mmHg) and arterial occlusion (AO, 250 mmHg); (3) recovery slopes (Rslope) for oxygen saturation (StO(2)) following isometric contractions and AO. For each variable, an intraclass correlation (ICC) was calculated to assess the ability to differentiate between subjects, and limits of agreement (LOA) were computed to assess day-to-day consistency of the measurement. ICCs for ΔStO(2)% were lowest at 10% MVC for both ECR (0.58) and TD (0.55), and highest at 30% MVC for ECR (0.95) and at 70% MVC for TD (0.79). For both muscles, LOA for ΔStO(2)% was lowest at 10% and highest at 50 and 70% MVC. ICC for HbTslope was 0.17. For HHbslope ICC was higher for AO (0.83) than for VO (0.73), and LOA was lower for AO. For the ECR Rslope ICCs ranged from 0.88 to 0.90 for contraction, but was lower for AO (0.33); LOA was lowest at 70% MVC. For trapezius Rslope ICCs ranged from 0.63 to 0.73 and LOA was lowest at 30% MVC. For this study, establishing reliability data for the ECR and TD and including variables commonly reported are expected to have meaning for future NIRS studies of work-related upper-extremity pain as well as for other NIRS research and clinical applications.

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Exercise-based rehabilitation programmes for pulmonary hypertension

Morris

Kermeen

Holland

2017

Cochrane Database of Systematic Reviews

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In people with PH, exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL, these may not be clinically important. Overall, we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH.

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Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

Cited by 30 publications

References 53 publications

Regional skeletal muscle remodeling and mitochondrial dysfunction in right ventricular heart failure

Regional skeletal muscle remodeling and mitochondrial dysfunction in right ventricular heart failure

Reliability of near-infrared spectroscopy for measuring forearm and shoulder oxygenation in healthy males and females

Exercise-based rehabilitation programmes for pulmonary hypertension

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