Heart Muscle Metabolism and Function during Heavy Exercise

Author(s):  
Lennart Kaijser
2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Malte Tiburcy ◽  
James E Hudson ◽  
Dirk Ziebolz ◽  
Wolfram H Zimmermann

Background: Tissue engineering of heart muscle from human pluripotent stem cells holds great potential for in vitro studies, disease modeling, and cardiac replacement therapy. A number of variables may however affect maturation and function of human cardiomyocytes (CM) in tissue engineered heart muscle (EHM). Here, we hypothesized that defined non-myocyte (NM) populations support structural and functional maturation of EHM. Methods and Results: To investigate the role of non-myocytes (NM) for heart muscle assembly in vitro we generated EHM from purified CM (93±1.5% actinin+) and a mixture of CM and NM (70/30%). Notably, only the NM-supplemented EHM generated measurable forces (0.8±0.1 mN, n=9) with anisotropically aligned cardiomyocytes. Depending on pluripotent stem cell line and differentiation protocol the NM compartment may vary considerably. To further define the influence of the NM compartment we generated EHM from HES2-derived CM with undefined NM, i.e the NM typically derived during cardiac differentiation, and defined NM (fibroblasts). Defined EHM were more mature with higher forces and lower variability between experimental series (defined: 9.8±0.9 nN/CM, undefined: 4.7±1.4 nN/CM, n=10/9), higher EC50 for calcium, and enhanced inotropic response to isoprenaline despite comparable CM:NM composition of 1:1. Increased actinin protein per CM, a reduction of MLC2V/2A double positive CM, and evidence of CM cycle withdrawal indicated enhanced ventricular maturation in defined EHM. Next, we tested whether defining cell composition and NM in iPS-derived EHM will yield a comparable functional phenotype to HES2-EHM. In agreement with the above data, defined iPS-EHM displayed advanced functional maturation with high specific forces, comparable calcium EC50, and inotropic response to isoprenaline. Summary and Conclusions: Here we demonstrate that defining the NM compartment is essential for optimized human heart muscle formation and maturation in vitro. Moreover, our data provide (1) evidence for the applicability of EHM in modelling of heart muscle development and (2) a strong rationale for the need to define CM and NM compartments in tissue engineered myocardium to reduce variability in applications such as disease modelling.


1999 ◽  
Vol 86 (6) ◽  
pp. 2077-2089 ◽  
Author(s):  
Loren A. Bertocci ◽  
Barbara F. Lujan

Skeletal muscle can utilize many different substrates, and traditional methodologies allow only indirect discrimination between oxidative and nonoxidative uptake of substrate, possibly with contamination by metabolism of other internal organs. Our goal was to apply 1H- and13C-nuclear magnetic resonance spectroscopy to monitor the patterns of [3-13C]lactate and [1,2-13C]acetate (model of simple carbohydrates and fats, respectively) utilization in resting vs. contracting muscle extracts of the isolated perfused rat hindquarter. Total metabolite concentrations were measured by using NADH-linked fluorometric assays. Fractional oxidation of [3-13C]lactate was unchanged by contraction despite vascular endogenous lactate accumulation. Although label accumulated in several citric acid cycle (CAC) intermediates, contraction did not increase the concentration of CAC intermediates in any muscle extracts. We conclude that 1) the isolated rat hindquarter is a viable, well-controlled model for measuring skeletal muscle13C-labeled substrate utilization; 2) lactate is readily oxidized even during contractile activity; 3) entry and exit from the CAC, via oxidative and nonoxidative pathways, is a component of normal muscle metabolism and function; and 4) there are possible differences between gastrocnemius and soleus muscles in utilization of nonoxidative pathways.


1984 ◽  
Vol 16 ◽  
pp. 30-30
Author(s):  
T ROBINSON ◽  
S FACTOR ◽  
E SCHWARTZ ◽  
J CAPASSO ◽  
L COHENGOULD ◽  
...  

2010 ◽  
Vol 119 (11) ◽  
pp. 465-466 ◽  
Author(s):  
P. Christian Schulze

Derangements in systemic and local metabolism develop in patients with CHF [chronic HF (heart failure)] and contribute to the progression of the disease. Impaired skeletal muscle metabolism, morphology and function leading to exercise intolerance are hallmarks of the syndrome of CHF. These changes result in abnormal glucose and lipid metabolism, and the associated insulin resistance, which contribute to progression of skeletal muscle catabolism and development of muscle atrophy in patients with advanced HF. In the present issue of Clinical Science, Toth and co-workers demonstrate the impairment of skeletal muscle protein metabolism in patients with HF, and specifically show an impaired anabolic response in the skeletal muscle of these patients following a period of nutritional deficiency.


1988 ◽  
Vol 412 (3) ◽  
pp. 336-337 ◽  
Author(s):  
H. Kaciuba-Uścilko ◽  
Z. Brzezińska ◽  
B. Kruk ◽  
K. Nazar

2021 ◽  
Vol 8 ◽  
Author(s):  
Chae-Eun Yun ◽  
Hyun-Kyung So ◽  
Tuan Anh Vuong ◽  
Myung Woo Na ◽  
Subin Anh ◽  
...  

Black chokeberry or aronia (the fruit of Aronia melanocarpa) has been reported to having pharmacological activities against metabolic syndrome, such as hypertension, obesity, diabetes, and pro-inflammatory conditions. However, the effects of aronia on myogenic differentiation and muscle homoeostasis are uncharacterized. In this study, we investigated the effects of aronia (black chokeberry) on myogenic differentiation and muscle metabolic functions in young mice. Aronia extract (AR) promotes myogenic differentiation and elevates the formation of multinucleated myotubes through Akt activation. AR protects dexamethasone (DEX)-induced myotube atrophy through inhibition of muscle-specific ubiquitin ligases mediated by Akt activation. The treatment with AR increases muscle mass and strength in mice without cardiac hypertrophy. AR treatment enhances both oxidative and glycolytic myofibers and muscle metabolism with elevated mitochondrial genes and glucose metabolism-related genes. Furthermore, AR-fed muscle fibers display increased levels of total OxPHOS and myoglobin proteins. Taken together, AR enhances myogenic differentiation and improves muscle mass and function, suggesting that AR has a promising potential as a nutraceutical remedy to intervene in muscle weakness and atrophy.


2020 ◽  
Vol 2 (9) ◽  
pp. 840-848 ◽  
Author(s):  
James Frampton ◽  
Kevin G. Murphy ◽  
Gary Frost ◽  
Edward S. Chambers

Author(s):  
E.G. KREBS ◽  
J.T. STULL ◽  
P.J. ENGLAND ◽  
T.S. HUANG ◽  
C.O. BROSTROM ◽  
...  

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