Exercise Training Alters Skeletal Muscle Mitochondrial Morphometry in Heart Failure Patients

Santoro, Cheryl; Cosmas, Arthur C.; Forman, D E; Morghan, Alia; Bairos, Lynn; Levesque, Sebrina; Roubenoff, Ronenn; Hennessey, James V.; Lamont, Linda S.; Manfredi, Thomas G.

doi:10.1177/174182670200900612

Cited by 17 publications

(15 citation statements)

References 26 publications

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“…2, 33, 43, 61,72,74,97,112,115,136,156,226,267,307,309) reflecting that the key signaling pathways for mitochondrial biogenesis and function, such as PGC-1␣ and calcineurin activation, are preserved in the skeletal muscle of CHF patients (90). Nonetheless, there are reports to the contrary (90,160,274,289,305,319,340).…”

Section: Exercising Blood-muscle O 2 Flux In Health and Chf: Mechanismentioning

confidence: 81%

Exercise training in chronic heart failure: improving skeletal muscle O₂transport and utilization

Hirai

Musch

Poole

2015

American Journal of Physiology-Heart and Circulatory Physiology

142

156

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Hirai DM, Musch TI, Poole DC. Exercise training in chronic heart failure: improving skeletal muscle O 2 transport and utilization. Am J Physiol Heart Circ Physiol 309: H1419 -H1439, 2015. First published August 28, 2015; doi:10.1152/ajpheart.00469.2015.-Chronic heart failure (CHF) impairs critical structural and functional components of the O 2 transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O 2 delivery and utilization (Q mO 2 and V mO 2 , respectively). The Q mO 2 /V mO 2 ratio determines the microvascular O2 partial pressure (PmvO 2 ), which represents the ultimate force driving blood-myocyte O 2 flux (see Fig. 1). Improvements in perfusive and diffusive O2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster V mO 2 kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O 2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal V mO 2 ). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved Q mO 2 /V mO 2 matching (and enhanced PmvO 2 ) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O 2 convection within the skeletal muscle microcirculation, O 2 diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary nitrate supplementation are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O 2 transport and utilization system underlie improvements in physical capacity and quality of life in CHF and thus take center stage in the therapeutic management of these patients.

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Section: Exercising Blood-muscle O 2 Flux In Health and Chf: Mechanismentioning

confidence: 81%

Exercise training in chronic heart failure: improving skeletal muscle O₂transport and utilization

Hirai

Musch

Poole

2015

American Journal of Physiology-Heart and Circulatory Physiology

142

156

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“…Also (cryo)-electron microscopy (EM) analysis of fixed specimens has been widely applied to analyze mitochondrial (ultra)structure (e.g. [41,[166][167][168]). As a consequence, morphometric analyses have been historically important to quantify mitochondrial properties using EM images [169].…”

Section: Quantification Of Mitochondrial Morphology and Contentmentioning

confidence: 99%

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Tronstad¹,

Nooteboom²,

Nilsson³

et al. 2014

CPD

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Running title: Regulation and quantification of mitochondrial morphology and content. Word count: 15,454 (total)Characters: 107,091 (including spaces); 92,067 (excluding spaces) Keywords: mitochondrial biogenesis, mitochondrial dynamics, mitochondrial degradation, living cells, TMRM, microscopy, segmentation, image analysis.Page 2 of 37 ABSTRACTMitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.

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“…Mitochondrial aberrations, resulting in a reduced mitochondrial capacity, may therefore seriously impair normal energy and substrate metabolism. Mitochondrial aberrations have not only been reported for metabolic disorders like Type 2 diabetes and obesity but also in diseases like chronic heart failure and chronic obstructive pulmonary disease (11,24).…”

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confidence: 99%

Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity

Hoed

Hesselink²,

Kranenburg³

2008

Journal of Applied Physiology

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den Hoed M, Hesselink MK, van Kranenburg GP, Westerterp KR. Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity. J Appl Physiol 105: 561-568, 2008. First published May 29, 2008 doi:10.1152/japplphysiol.00091.2008.-Physical exercise training is a powerful tool to maintain or improve mitochondrial density and function (mitochondrial capacity). This study aims to determine whether mitochondrial capacity is also associated with habitual physical activity in daily life (PA DL). The capacity of classic markers for mitochondrial density, i.e., the capacity of citrate synthase (CS) and succinate dehydrogenase (SDH), as well the capacity of cytochrome c oxidase (COX) and ␤-hydroxyacyl-CoA dehydrogenase (HAD), was determined in homogenized muscle biopsy samples obtained from the vastus lateralis muscle of nonexercising healthy young (age 20 Ϯ 2 yr) subjects (31 women, 7 men). PA DL was measured during two periods of 14 days using a triaxial accelerometer for movement registration. CS, SDH, and COX were positively associated with PA DL [P Ͻ 0.05, R ϭ 0.36, 95% confidence interval (CI): 1.3 ⅐ 10 Ϫ4 to 2.2 ⅐ 10 Ϫ3 ; P Ͻ 0.05, R ϭ 0.39, 95% CI: 1.1 ⅐ 10 Ϫ5 to 9.9 ⅐ 10 Ϫ5 ; and P Ͻ 0.05, R ϭ 0.33, 95% CI: 7.5 ⅐ 10 Ϫ6 to 3.6 ⅐ 10 Ϫ4 , respectively], and HAD tended to correlate positively with PA DL (P ϭ 0.06, R ϭ 0.31, 95% CI: Ϫ2.2 ⅐ 10 Ϫ5 to 1.1 ⅐ 10 Ϫ3 ). The population was subsequently stratified based on the intensity of the activities performed. CS was only associated with PADL in subjects spending more time on high-intensity physical activity, whereas HAD was only associated with PADL in subjects spending less time on low intensity physical activity. We are the first to report that even within the range of normal daily life activities, mitochondrial capacity is positively associated with the level of habitual physical activity in daily life. Thus an active lifestyle may help to maintain or improve mitochondrial capacity. accelerometer; intensity; citrate synthase; succinate dehydrogenase; cyctochrome c oxidase; ␤-hydroxyacyl-CoA dehydrogenase IN WESTERNIZED SOCIETIES, the prevalence of Type 2 diabetes and obesity has increased significantly over the past few decades (18,25). A decreased physical activity has been associated with both Type 2 diabetes (13, 17) and obesity (15). Part of the pathophysiology related to these diseases has been attributed to a reduced mitochondrial capacity: the product of mitochondrial density and function (2,16,22).Mitochondria are vital organelles in the oxidative degradation of macronutrients to maintain cellular ATP levels. Mitochondrial aberrations, resulting in a reduced mitochondrial capacity, may therefore seriously impair normal energy and substrate metabolism. Mitochondrial aberrations have not only been reported for metabolic disorders like Type 2 diabetes and obesity but also in diseases like chronic heart failure and chronic obstructive pulmonary disease (11, 24).Proper mitochondrial function and maintenance of mitochondrial capac...

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Exercise Training Alters Skeletal Muscle Mitochondrial Morphometry in Heart Failure Patients

Cited by 17 publications

References 26 publications

Exercise training in chronic heart failure: improving skeletal muscle O₂transport and utilization

Exercise training in chronic heart failure: improving skeletal muscle O₂transport and utilization

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity

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Exercise Training Alters Skeletal Muscle Mitochondrial Morphometry in Heart Failure Patients

Cited by 17 publications

References 26 publications

Exercise training in chronic heart failure: improving skeletal muscle O2transport and utilization

Exercise training in chronic heart failure: improving skeletal muscle O2transport and utilization

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity

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Resources

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Exercise training in chronic heart failure: improving skeletal muscle O₂transport and utilization

Exercise training in chronic heart failure: improving skeletal muscle O₂transport and utilization