bluuebunny/crossref_metadata_2025 huggingface dataset:
Not all skeletal muscle fibers depend on the myoprotection of KATP channels during fatigue (1102.15)
Authors: Renaud Jean‐Marc , Selvin David
Published: June 2021

During fatigue, KATP channels are crucial in reducing action potential amplitude to eventually lower Ca2+ release by sarcoplasmic reticulum, which helps preserve ATP during a metabolic stress by decreasing Ca2+ ATPase and myosin ATPase activity. In the absence of KATP channel activity, skeletal muscle muscles suffer major contractile dysfunctions, which lead to faster fatigue rate because of fiber damage. In our studies at 37°C, we have observed a tremendous variability in the fatigue kinetics among mouse single FDB muscle fibers. Under control conditions, such variability is expected as fatigue resistance is in the order of type I>IIA>IIX>IIB (note IIB fibers are not present in FDB). However, we also observed a large variability in fatigue kinetics when KATP channels are completely blocked with 10 µM glibenclamide. Our results suggest that the importance of the KATP channel for myoprotection during fatigue is in the order of type IIX > IIA > I types, an order similar to the difference in KATP channel content between fiber types; i.e., the KATP channels are the most important in glycolytic fibers and the least important in oxidative fibers.

Grant Funding Source: NSERC
CD34 in skeletal muscle regeneration in chronic obstructive pulmonary disease (1102.20)
Authors: Pagé Mélissa , Langlois Anick , Porlier Alexandra , Thériault Marie‐Ève , Dubé Annie , Debigaré Richard , Blanchet Marie‐Renée
Published: June 2021

Chronic obstructive pulmonary disease (COPD) is associated with inflammation, irreversible airflow obstruction and muscular atrophy. Recently, it was shown that muscular atrophy in COPD is linked with alterations in satellite cell function which are the primary myogenic source contributing to skeletal muscle regeneration. The satellite cell‐marker CD34 plays a role in cell movement and muscle repair in toxin‐induced muscle injury. However, the link between CD34 expression and muscle regeneration in COPD has never been studied. Our hypothesis is that the inflammatory and hypoxic conditions found in COPD influence the expression of CD34 by satellite cells and affect muscle regeneration. The expression of CD34 was detected 1) in human satellite and C2C12 cell cultures in response to hypoxic or inflammatory conditions and 2) in muscle biopsies obtained from COPD or healthy subjects. Results show that CD34 expression in muscle decreases with COPD severity. Surprisingly, hypoxic and inflammatory conditions increased CD34 expression in cells, while myosin expression was reduced. This suggests that inflammatory and hypoxic stress increase CD34 expression in skeletal muscle cells which return to a satellite cell‐like phenotype. It also suggests an interesting role for CD34 in the response to hypoxic and inflammatory conditions, and a potential role for CD34 in muscle atrophy in COPD.
Wnt3a potentiates myogenesis in C2C12 myoblasts through the modulation of intracellular calcium and activation of the β‐catenin signaling pathway (1102.23)
Authors: Huang Jian , Mo Chenglin , Bonewald Lynda , Brotto Marco
Published: June 2021

Our research group has been investigating the biochemical crosstalk between bones and muscles. Wnts are secreted by bone cells and have a significant potential to directly influence muscle function. Our previous studies demonstrated potent myogenic effects of Wnt3a at a concentration of 10ng/ml. We now present new evidence that as low as 0.5ng/ml can significantly increase myogenic differentiation, which was confirmed morphologically and immunohistochemically. Wnt3a also promoted translocation of β‐catenin to the nucleus of myocytes/myotubes, suggesting that Wnt3a might lead to the downstream activation of muscle regulatory factors. Intriguingly, the potent effect of Wnt3a on stimulating the activation of the β‐catenin signaling pathway in C2C12 cells strongly correlated with the appearance of intracellular calcium oscillations in myotubes measured with Fura‐2. In agreement, focused qRT‐PCR arrays revealed a 6‐fold increase in IP3‐R1 and IP3R3, also revealed that Wnt3a promoted overexpression of myogenic markers (MyoD, MyoG, MHC), and downstream genes of the β‐catenin pathway (Fhl1 and Numb). We propose that Wnt3a acts through the modulation of intracellular calcium, resulting in translocation of β‐catenin that in turn enhances expression of muscle regulatory factors.

Grant Funding Source: NIH‐NIA P01 AG039355 (LB, MB), Dale and Dorothy Thompson Endowment Fund (MB) and Missouri Life Scien
Physical inactivity promotes contractile dysfunction at the whole tissue, cellular and molecular levels in older adults (1102.29)
Authors: Callahan Damien , Miller Mark , Beynnon Bruce , Slauterbeck James , Toth Michael
Published: June 2021

Age‐related deficits in skeletal muscle function are likely potentiated by corresponding reductions in volitional physical activity. Our objective was to investigate the effects of chronic muscle disuse by comparing structural and functional properties of skeletal muscle between healthy older adults with limited physical mobility secondary to knee osteoarthritis (Disuse; n=16) and healthy, recreationally‐active older adults (Controls; n=15). Knee extensor strength and cellular and molecular contractile characteristics were assessed from vastus lateralis muscle biopsies. Isometric and isokinetic knee extensor strength were reduced (34‐43%; p<0.01 for all) with disuse, as was single fiber force production in MHC I (18%; p 0.1 for all). Myosin‐actin cross‐bridge kinetic parameters were reduced in MHC I with disuse, as evidenced by prolonged actin‐myosin attachment time (+20%; p <0.01), but not in MHC IIA or IIA/X fibers. A strong trend towards more (+23%; p = 0.06) strongly‐bound cross‐bridges was observed in MHC I fibers with disuse. Considering similar MHC I tension between groups, these data suggest intrinsic impairments in molecular level force production/transmission with disuse. In summary, although cellular level deficits in force production are explained by atrophy, molecular level changes, which are independent of fiber size, may contribute to impaired whole muscle performance observed with chronic muscle disuse.

Grant Funding Source: Supported by NIH AG033547
Exon 12 of slow skeletal troponin t affects calcium sensitivity of force development and interactions with other thin filament components (1102.30)
Authors: Pinto Jose Renato , Xu Qian , Parvatiyar Michelle , Oh Won Chan , Potter James , Gomes Aldrin
Published: June 2021

Little information exists concerning the functional roles of the human slow skeletal troponin T isoforms (HSSTnT isoforms) in slow skeletal muscle. Three HSSTnT isoforms have been found in human slow skeletal muscle: HSSTnT1 (+ exons 5 and 12), HSSTnT2 (+5, ‐12), and HSSTnT3 (‐5, ‐12). Another potential isoform HSSTnT‐Hyp (‐5, +12) was recently found at the mRNA level. The objective of this study was to determine the physiological role of these SSTnT isoforms in slow skeletal muscle. To investigate these SSTnT isoforms several methods including skinned fiber mechanics, peptide spot blot, and mammalian two‐hybrid assays were utilized. Skinned rabbit slow soleus muscle fibers were displaced with HSSTnT1, 2, 3 or Hyp and reconstituted with the human slow skeletal troponin I (HSSTnI)/human cardiac troponin C (HCTnC) complex. The calcium sensitivity increased between SSTnT isoforms: isoform 1 (pCa50 = 5.74) < Hyp isoform (pCa50 = 5.80) < isoform 2 (pCa50 = 5.81) < isoform 3 (pCa50 = 5.84). In a reconstituted skeletal muscle system, the HSSTnT 1‐3 isoforms had similar actomyosin ATPase activation or inhibition in the presence or absence of calcium. Peptide spot blot analysis revealed novel interactions between HSSTnT peptides and HCTnC, RSTm and HCTnI. Mammalian two‐hybrid studies showed that the alternatively spliced regions affect the interaction of HSSTnT with other thin filament components. These results suggest that the functional differences that occur between HSSTnT isoforms may be partially due to alternative splicing of exon 12. Overall, HSSTnT isoforms were found to have distinct functional properties in slow skeletal muscle regulation and are likely to be relevant for the understanding of skeletal muscle diseases.

Grant Funding Source: UC Davis research funds and NIH
Effects of total knee arthroplasty on markers of muscle damage two hours after surgery (1102.33)
Authors: Hocker Austin , Jewett Brian , Shah Steven , Lantz Brick , Dreyer Hans
Published: June 2021

Total knee arthroplasty (TKA) results in rapid muscle atrophy, decreased strength, and functional mobility limitations. Our prior reports on the acute effects of ischemia and reperfusion during TKA suggests decreased protein synthesis, increased protein degradation, and activation of the endoplasmic reticulum (ER) stress response in skeletal muscle. The purpose of this experiment was to determine if protein and transcript markers of protein synthesis, degradation, and ER stress remained elevated two hours after TKA. We studied 60‐80 year old patients before and two hours after primary TKA. Muscle biopsies were obtained in the operating room immediately before tourniquet application, at maximal ischemia, and two hours after reperfusion. Our preliminary data show the fraction of spliced XBP1 transcript increased 124% during ischemia (p = .11) and 104% after reperfusion (p < .05) relative to baseline. Protein levels of phosphorylated 4EBP1 (Thr37/46) decreased 34% during ischemia (p < .05) and 20% after reperfusion (not significant) relative to baseline. Phosphorylation of AKT (Ser473) decreased 69% during ischemia (p = .10) and nearly returned to baseline after reperfusion. Interestingly, transcript levels of ATF4 and BIP were decreased during both ischemia and recovery (p < .05) and ERDJ4 and CHOP expression was not significantly different relative to baseline during ischemia or after reperfusion. Two hours after TKA muscle cell cross sectional area was increased 34% relative to baseline. These preliminary results suggest that ischemia and reperfusion during TKA induce changes in muscle metabolism that persist two hours after surgery.

Grant Funding Source: Supported by K01HD057332
Hypoxia regulated expression of erythropoietin in cultured myoblasts and myotubes (1102.35)
Authors: Baker Jeff , Parise Gianni
Published: June 2021

Erythropoietin (EPO) is responsible for supporting the growth and development of red blood cells. EPO is produced mainly by the kidney and its expression is regulated by hypoxia. Several studies have assessed the ability of skeletal muscle to produce EPO, using whole muscle biopsies, and have observed conflicting results. Here, cell culture, RT‐PCR, and flow cytometry were used. The objective was to determine if myoblasts and myotubes were capable of expressing EPO, how its expression might be regulated, and if skeletal muscle was capable of supporting erythropoiesis in vitro. qPCR analysis demonstrated positive expression of EPO in myoblasts and myotubes. EPO expression was not modulated by physiological variables common to working muscle such as mechanical stimulation, pH, or temperature. Hypoxia, however, increased EPO expression in myoblasts by 2.2 fold (p < 0.05) and myotubes by 1.5 fold (p < 0.05). When myoblasts were conditioned with hypoxia, media taken from them was able to support erythropoiesis in bone marrow cultures. 72 hours after treatment with hypoxic myoblast conditioned media, Ter‐119 positive cells in bone marrow culture were increased by 20% (p < 0.05). These results suggest that both myoblasts and myotubes are capable of expressing EPO and do so in a hypoxia dependent manner. As well, these results lend support to studies that have observed increases in circulating levels of EPO following endurance exercise interventions, where skeletal muscle oxygen saturation is known to drop to hypoxic levels.
Bone marrow inoculation of Walker 256 tumor cells in rats as a model of cancer cachexia (1102.36)
Authors: Alves Christiano , de Almeida Ney , das Neves Willian , Gutierrez Vanessa , Voltarelli Vanessa , Cury Yara , Gualano Bruno , Seelaender Marília , Lancha Junior Antonio , Brum Patricia
Published: June 2021

Bone marrow inoculation of Walker 256 tumor cells in rats as a model of cancer cachexia Christiano R. R. Alves, Ney R. de Almeida, Willian das Neves, Vanessa P. Gutierrez, Vanessa Voltarelli, Yara Cury, Bruno Gualano, Marília Seelaender, Antonio H. Lancha Junior, Patricia C. Brum. University of São Paulo, São Paulo, Brazil.

The aim of this study was to standardize a model of cancer cachexia in rats by inoculating Walker 256 tumor cells in bone marrow. Male Wistar rats were inoculated with Walker 256 tumor cells in the bone marrow by an osteotomy in femur (Walker group). Control rats were submitted to sham osteotomy (Control group). Walker was compared to the Control group by unpaired Student's t‐test. The significance level was previously set at p < 0.05. After the osteotomy, Walker group showed 16 days of survival on the average with 100% mortality rate after 23 days paralleled by lower body mass (‐8.8%; p = 0.03) and food intake (‐30.1%; p < 0.001) than Control group. In addition, Walker group decreased in vivo skeletal muscle function, assessed by both treadmill maximal incremental test (‐52.7%) and deambulation test (‐21.1%) (p < 0.001). Walker group displayed plantaris, gastrocnemius and triceps atrophy (p < 0.05 for all), which was not observed in soleus (p > 0.05). Additionally, lower citrate synthase activity and oxidized/reduced glutathione ratio were observed in plantaris (p < 0.05) but not in soleus (p > 0.05) of Walker group. These data provide evidence for oxidative metabolism dysfunction and redox imbalance in muscles with predominance of glycolytic fibers (i.e. plantaris), but not in muscles with predominance of oxidative fibers (i.e. soleus). Collectively, our results suggest that bone marrow inoculation of Walker 256 tumor cells in rats is a new model of severe cancer‐induced muscle atrophy selective to glycolytic fibers.

Grant Funding Source: FAPESP (process: 2012/02528‐0)
AT1 receptor blocker attenuates mechanical ventilation‐induced atrophy and oxidative stress in the diaphragm muscle (1102.39)
Authors: Kwon Oh‐Sung , Smuder Ashley , Sollanek Kurt , Wiggs Michael , Talbert Erin , Scott Powers
Published: June 2021

Background: Mechanical ventilation (MV) is a method of maintaining adequate gas exchange in patients who are unable to sustain adequate alveolar ventilation on their own. Recently, our lab demonstrated that Angiotensin II (Ang II) is a possible mechanism that causes MV‐induced diaphragm muscle atrophy. During MV, elevation of Ang II induces Reactive Oxygen Species (ROS) emission from mitochondria and results in activation of key proteases, calpain and caspase‐3, in the diaphragm. To determine Ang II is a required upstream signal for MV‐induced diaphragm muscle atrophy and contractile dysfunction, we used AT1 receptor blocker (Losartan) and ACE inhibitor (Enalapril), which prevent the elevation of plasma Ang II levels during MV.

Methods: Adult female rats were randomly assigned to one of six experimental groups (n =12 each) (1) Spontaneous breathing (SB) with salin, (2) SB with Losartan (LOS), (3) SB with Enalapril (ENA), (4) MV with salin, (5) MV with LOS, (6) MV with ENA. Dependent measures included plasma Ang II levels, diaphragmatic muscle fiber cross‐sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm.

Results: ENA attenuates increased circulating Ang II levels during 12 hours prolonged MV but LOS does not. However, only LOS attenuated MV‐induced diaphragm muscle atrophy. As well as, LOS attenuated MV‐induced mitochondrial dysfunction, ROS production, and proteasome activity during.

Therefore, Ang II does not appear to be a possible upstream mechanism to prevent MV‐induced diaphragm muscle atrophy. AT1 receptor blocker, losartan has an antioxidant effect and attenuates MV‐induced VIDD. Therefore, the results of our experiments could lead to human clinical trials using losartan as a therapeutic intervention to prevent VIDD.
LAT1 muscle‐specific knockout limits early load‐induced mTORC1 activity (1102.41)
Authors: Aguirre Nicholas , Baar Keith
Published: June 2021

Leucine exhibits a strong anabolic effect in skeletal muscle: increasing muscle protein synthesis via activation of mechanistic target of rapamycin‐complex 1 (mTORC1). Since LAT1 is the primary leucine transporter in skeletal muscle, its regulation could affect anabolic resistance. The purpose of this study was to elucidate the role of LAT1 muscle‐specific knockout (mKO) on mTORC1 activity after acute loading. Three month old control (CON; n = 11) and LAT1 mKO mice (mKO; n = 12) were anesthetized and unilaterally loaded. Tibialis anterior muscles were collected bilaterally 30 min, 3 h and 18 h post‐loading and mTORC1 activity was determined using western blot analysis of phospho/total S6K1 389 (pS6K1). pS6K1 increased 30 min and 3 h post‐loading from non‐stimulated limbs (NS) to stimulated limbs (S) for CON (30 min: NS: 0.98 ± 0.11, S: 3.46 ± 0.36, p < 0.01; 3 h: NS: 0.98 ± 0.23, S: 9.95 ± 1.58, p < 0.01) and mKO (30 min: NS: 1.16 ± 0.13, S: 1.74 ± 0.52, p = 0.27; 3 h: NS: 1.08 ± 0.14, S: 7.75 ± 1.99, p < 0.01). Stimulated pS6K1 was higher in CON than mKO at 30 min (p < 0.05) post‐loading. We conclude LAT1 mKO limits early mTORC1 activation and might contribute to anabolic resistance post‐loading.
Role of small heat shock proteins in muscle under chronic hyperglycemia (1102.42)
Authors: Reddy Vadde , Reddy Geereddy
Published: June 2021

Role of small heat shock proteins in muscle under chronic hyperglycemia V. Sudhakar Reddy1, G. Bhanuprakash Reddy1 1Department of Biochemistry, National Institute of Nutrition, Hyderabad, India Objective: To study the expression of small heat shock proteins (sHsp) and their localization in diabetic rat muscle.

Methods: Diabetes was induced in rats and maintained on hyperglycemia for a period of 12 weeks. The expression of sHsp and phosphorylated sHsp was analysed by qRT‐PCR, immunoblotting. The translocation of phosphorylated sHsp (pS82‐Hsp27, pS59‐αB‐crystallin; αBC) was analyzed by detergent solubility assay and co‐immunoprecipitation. The cell death was analysed by assessing the levels bcl‐2, bax and cleaved caspase‐3. The interaction of αBC with bax was analyzed by co‐immunoprecipitation Results: Out of 10 sHsp, 7 sHsp were detected in muscle. Among them, increased expression of αBC was seen diabetic muscle. Furthermore, detergent soluble assay and co‐immunoprecipitation studies confirmed the translocation and interaction of phosphorylated sHsp with cytoskeleton (desmin) under diabetic conditions. Diabetes induced the cell death as assessed by the levels of cleaved caspase‐3, bax and bcl‐2. Moreover, diabetes reduced the interaction of αBC with bax.

Conclusion: There was increased expression of αBC under hyperglycemic conditions. Further, chronic hyperglycemia induced the translocation of pS82‐Hsp27 and pS59‐αBC from cytoplasm to a striated sarcomere at or near z‐lines and intercalated discs. Altered interaction of αBC with bax seems to influence cell death in diabetic muscle.
Myostatin expression and high fat diet effects on skeletal muscle and adipose metabolism in mouse (1102.45)
Authors: Constantinescu Silvana , Abraham Andrea , Reisz‐Porszasz Suzanne
Published: June 2021

We explored the effects of myostatin (Mst) expression and high fat diet (HFD) on skeletal muscle (SM) and adipose tissues (AT) metabolic profiles in transgenic mice overexpressing Mst (TG). To investigate the effects of Mst on SM and AT in wild‐type (WT) and TG mice, and the correlation between Mst and insulin resistance, we measured mRNA levels and protein expression of Mst, several intermediates from the insulin signaling pathway and analyzed the metabolic profile of both tissues using METABOLON. Methods: Adult male mice (6 mice/group) were kept on control diet (CD) and HFD for 4 weeks; glucose tolerance was measured before and after the diet; blood, SM and AT were collected. Results: Metabolon heat‐map analysis showed that Mst in TG mice on CD or HFD increased (95%; P<0.05) several glycolytic intermediates in SM suggesting that glycolysis and glucose uptake is elevated by Mst overexpression. TG mice on CD had lower (P>0.05) levels of free fatty acids (FFAs) compared to WT in SM and AT. HFD increased (25%) the levels of FFAs in SM compared to AT in WT and TG. Conclusion: WT‐SM responded to HFD with a rise (62%) in fatty acid oxidation (FAO); TG‐SM with HFD showed no change (P>0.05) in FAO. TG‐AT responded to HFD with a rise in triacylglycerol synthesis (12%) and a decrease in FAO. These data suggest that genetic modification of Mst expression affected primarily SM glucose utilization parallel with decreased FAO in AT in adult mice.

Grant Funding Source: NIH/NIGMS: SC1GM089648
Muscle fibrosis due to loss of desmin increases muscle stiffness due to an increased number of perimysial collagen cables (1102.8)
Authors: Gillies Allison , Lieber Richard
Published: June 2021

Skeletal muscle stiffness increases with injury and disease, yet the structural basis of stiffness is unknown. The purpose of this study was to quantify perimysial collagen in a model of skeletal muscle fibrosis (desmin knockout, des‐/‐) to determine if increased stiffness correlates with increased volume fraction of these structures. Stereology was performed on mouse 5th toe extensor digitorum longus (EDL) muscles to quantify perimysial collagen volume fraction and mechanical testing was performed to determine muscle stress at incremental sarcomere lengths. Stereology indicated a significantly higher volume fraction of collagen fibrils in cables in des‐/‐ compared to wt (Table 1). Tangent stiffness of des‐/‐ compared to wt (Fig. 1) was four times greater (p<0.05). In des‐/‐ muscle, perimysial collagen cable volume increased concurrent with stiffness while no increase was observed in endomysial collagen, implicating the perimysial collagen structures in increased stiffness at the whole muscle level, not just increased collagen in general. These results suggest that therapies targeting perimysial collagen cables may improve function in fibrotic skeletal muscle.

Table 1. Volume fraction of muscle components as percent EDL volume. Mean ± SEM, *p<0.05.

Muscle Component
Wild type (n = 8)
Desmin knockout (n = 8)

Myofibrils
59.2 ± 2.4
59.2 ± 2.8

Mitochondria
9.53 ± 0.8
8.20 ± 1.0

Myonuclei
0.55 ± 0.07
0.78 ± 0.13

Satellite cells
0.02 ± 0.009
0.009 ± 0.009

Fibroblasts
0.59 ± 0.14
0.74 ± 0.11

Single collagen fibrils
1.51 ± 0.31
1.26 ± 0.13

Collagen fibrils in cable
2.45 ± 0.26
4.15 ± 0.55*

Basement membrane
2.18 ± 0.23
1.83 ± 0.08
Physiological heart rate profile of hyperbaric underwater worker during an exercise stress testing as a predictor of physical fitness (1103.1)
Authors: Duvallet Alain , Duvallet Emilie , Lhuissier François , Constantin Pascal , Beaudry Michele
Published: June 2021

Aims: Study the possibility of abnormalities of heart rate with increased risk of sudden death or myocardial infarction is an important health burden in occupational or hyperbaric medicine Method: We studied the heart rate (HR) of 200 apparently healthy underwater workers during and after 780 bicycle exercise stress tests, recommended for medical fitness. The results were analysed step by step by mean, standard deviation and normal distribution. Results: For maximal power (range 99‐249 watts) the average of HR were at 98 ± 7.4 % of FMT. The HR had a continuous probability distribution at each step The variations above or below two standard deviation are defined as an abnormal response These patients have a temporary medical contraindication before special re‐assessments. Conclusion: The cardiovascular system should be sufficient to enable the underwater workers to sustain activity without increased risk. Exercise testing cannot exclude all cardiac risk; but the HR behavior was recommended for medical fitness. It should be especially, indeed, the consequences of injury are important and dangerous This finding should be considered in future cardio‐vascular guidance documents applied for a specific population
Physiological systemic pressure profile of hyperbaric underwater worker during exercise stress testing as a predictor of physical fitness (1103.2)
Authors: Duvallet Alain , Duvallet Emilie , Lhuissier François , Constantin Pascal , Beaudry Michele
Published: June 2021

Aims: Study the possibility of abnormalities in the control of blood pressure with increased risk of sudden death or myocardial infarction is an important health burden in occupational or hyperbaric medicine. Methods: To explore we studied the PAS and PAD of 200 apparently healthy underwater workers during 780 bicycle exercise stress tests. The results were analysed by mean, standard deviation and normal distribution. Results: The PASmax were at 212.4 ± 19.7 and PADmax at 98.8 ± 16.6 mmHg. All parameters have a continuous probability distribution at each step. The variations above or below two standard deviation defined an abnormal response. These patients have a temporary medical contraindication before special re‐assessments. Conclusion: The vascular system should be sufficient to enable the workers to sustain strenuous activity without increased risk and with a preserved systemic pressure. It should be especially stringent because the consequences of injury are important and dangerous Exercise testing cannot exclude all risk; but the blood pressure behavior was recommended for medical fitness. This finding should be considered in future cardio‐vascular guidance documents applied for a specific population.
Lower body negative pressure counters headward fluid shifts in the brain and eye (1103.3)
Authors: Macias Brandon , Grande Gutierrez Noelia , Hargens Alan , Liu John
Published: June 2021

Recent ophthalmic evaluations of 7 astronauts after 6‐month missions to International Space Station show unexpected vision impairment. In addition, lumbar punctures in 4 astronauts with optic disc edema showed moderate elevations of cerebral spinal fluid pressure after returning to Earth. This Visual Impairment Intracranial Pressure (VIIP) syndrome is likely due to a head‐ward body fluid shift that elevates intracranial pressure (ICP). We hypothesized that a moderate level of lower body negative pressure (LBNP) would counteract headdown, body‐tilt, induced elevations in intraocular pressure (IOP) and ICP. Seven healthy non‐smoking volunteers participated in this study (mean age: 36 years). Right and left IOP, ICP (ultrasound pulse phase lock loop), arm blood pressure, and heart rate were measured during the last minute of each testing condition. Subjects were positioned supine (5 mins), sitting (5 mins), 15‐degrees head‐down tilt (HDT) (5 mins) and ten minutes of HDT with LBNP (25 mmHg). The order of HDT and HDT+LBNP tests were balanced. The right and left IOP values were averaged and used for statistical analysis (p<0.05). Data are presented as mean ± standard deviation. The change from supine was calculated for IOP values. IOP significantly decreased from supine to sitting posture by 2.4 ± 0.7 mmHg, and increased by 1.3 ± 2.4 mmHg from supine to the HDT position. LBNP during head‐down‐tilt significantly lowered IOP to supine levels (difference from supine, 0.1 ± 0.8 mmHg). In addition, added LBNP during HDT significantly decreased ICP pulse amplitudes by 2.8±4.3 microns. Mean blood pressure and heart rate did not change significantly across all conditions. These data demonstrate that short duration exposures to HDT increase IOP and ICP significantly and further, that LBNP counteracts these elevations of IOP and ICP. Therefore, LBNP may help counteract vision impairments in space. Supported by NSBRI postdoctoral fellowship (BRM), la Caixa fellowship (NNG), and NASA grant NNX13AJ12G (ARH).
Leucine supplementation partially preserves neuromuscular activation during bed rest (1103.5)
Authors: Mettler Joni , Doucet Barbara , English Kirk , Bennett Sydney , Paddon‐Jones Douglas
Published: June 2021

We examined the effect of leucine supplementation on neuromuscular activation of sub‐maximal and maximal voluntary muscle contraction (MVC) in middle‐aged adults during 14 days of bed rest (BR). Participants (n = 10, 50.4 ± 1.0 y) in this randomized, double‐blind control 14 day BR study were assigned to a leucine (LEU, 0.06 g∙kg∙meal‐1 leucine) or control (CON) group. Surface electromyography (EMG) and torque were recorded from the vastus lateralis muscle during isometric knee extension at 20% (10s) and at 50%, 80% and 100% MVC (5s each) pre‐post BR and analyzed for root mean square (RMS) and median frequency (MF) EMG. Following BR, MVC (p < 0.001) decreased in both groups with no difference between groups. RMS EMG during 100% MVC decreased in CON post‐BR (p < 0.05), but was maintained in LEU and no difference in MF EMG pre‐post BR for either group (p > 0.05). Despite the decrease in MVC in both groups, CON RMS EMG was higher post‐BR during all sub‐maximal contractions while LEU RMS EMG did not change at 20% and was lower at 50% and 80% MVC post‐BR. Leucine may facilitate neuronal protective mechanisms that preserve motor neuron excitability and attenuate strength loss during prolonged physical inactivity.

Grant Funding Source: Supported by NSBRI NNJ08ZSA002N, NIA P30 AG024832, NIH 1UL1RR029876‐01
Effects of physical training on thermoregulation during exercise in spontaneously hypertensive rats (1104.1)
Authors: Santiago Henrique , Leite Laura , Lima Paulo Marcelo , Prímola‐Gomes Thales , Rodrigues Ana Cristina , Coimbra Cândido
Published: June 2021

The influence of physical training on heat balance and exercise performance in spontaneously hypertensive rats (SHR) was assessed. After physical training (8 wks), trained (T) and untrained (UT) SHR (n=6) and control Wistar rats (n=8) were submitted to incremental running until fatigue while body (Tb) and tail (Ttail) temperatures were recorded. T animals had increased workload (10.2 ± 0.7 kgm SHR‐T vs 5.9 ± 0.3 kgm SHR‐UN, 22.9 ± 1.4 kgm Wistar‐T vs. 10.9 ± 0.8 kgm Wistar‐UN; p < 0.05), however, SHR‐T and SHR‐UN demonstrated a reduction of 42% and 31%, respectively, in time of exercise in comparison with corresponding controls (p < 0.05). Tb increase was similar during exercise within the same lineage but SHR exhibited higher Tb variation from 14 min of exercise until fatigue (2.4 ± 0.2 °C SHR‐T vs. 1.4 ± 0.1 °C Wistar‐T; 1.8 ± 0.1 °C SHR‐UN vs. 1.1 ± 0.2 °C Wistar‐UN; p < 0.05). Moreover, although all groups had similar Ttail variation during exercise, SHR had lower Ttail at fatigue (30.1 ± 0.4 °C SHR‐T vs. 31.4 ± 0.3 °C Wistar‐T; 29.1 ± 0.5 °C SHR‐UN vs. 31.0 ± 0.3°C Wistar‐UN; p < 0.05), indicating an inferior vasodilation potential. The data show that hypertension aggravates the exercise‐induced hyperthermia due to lower heat dissipation through tail vasodilation, which contributes to the reduction in exercise performance.

Grant Funding Source: CNPq, FAPEMIG and CAPES
Determinants of core temperature thresholds for exercise ventilation (1104.23)
Authors: White Matthew , Yogev Assaf , Beaudin Andrew , Martin Des , Walsh Michael
Published: June 2021

Correlation and multiple regression analysis were employed to assess for human physical and physiological predictors of esophageal temperature (TES) thresholds for pulmonary ventilation during exercise (VE). It was hypothesized these TES thresholds would be positively associated to peak oxygen consumption (VO2PEAK) and thermolytic responses as well as negatively associated to the chemosensitivity of breathing. The SFU Office of Research Ethics approved the study. Twenty‐three volunteers participated 2 studies. They were 27.8±7.9 years of age (mean ± SD), 71.9±7.2 kg in weight and 1.76±0.06 m in height. They had a Body Surface Area (BSA) of 1.87±0.1 m2 and a Body Mass Index (BMI) of 23.4±2.4 kg/m2. Twenty‐three volunteers performed incremental cycle ergometer exercise from rest to the point of exhaustion. A second group of 9 volunteers performed a hyperoxic‐hypercapnic, modified Read rebreathing test during normothermia and hyperthermia. For correlation and multiple regression analyses the dependent outcome variables were TES thresholds for ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2). For the same analyses the independent variables included age, weight, height, BSA, BMI, VO2PEAK, the ventilatory recruitment threshold and slope from Read rebreathing plots and TES thresholds for onsets of eccrine sweating (ESW) and cutaneous blood velocity (CBV). Results indicated significant positive correlations between TES thresholds for VE/VO2 and VE/VCO2 with VO2PEAK (both r=0.42, p<0.05) and each of the TES thresholds for the onset of ESW and CBV (0.72<r<0.78, p<0.01). Multiple regression analysis gave the TES threshold for ESW as the single significant predictor of TES thresholds for VE/VO2 and VE/VCO2 (both R=0.72, p<0.05). In conclusion, TES thresholds for exercise ventilation were positively associated to VO2PEAK and prediction of these ventilation thresholds were made with TES thresholds for eccrine sweating.

Grant Funding Source: Supported by NSERC and CFI
Temperature affects maximum H‐reflex amplitude but not homosynaptic postactivation depression (1104.24)
Authors: Racinais Sebastien , Cresswell Andrew
Published: June 2021

This study aimed to determine the effect of hyperthermia on transmission efficacy of the Ia‐afferent spinal pathway. Recruitment curves of the Hoffman reflex (H‐reflex) and compound motor potential (M‐wave), and homo‐synaptic post‐activation depression (HPAD) recovery curves were obtained in 14 volunteers during normothermia (CON, ~37.3ºC) and hyperthermia (HOT, core temperature clamped at ~39.0ºC). Electromyographic responses were obtained from the soleus (SOL) and medial gastrocnemius (MG) muscles following electrical stimulation of the tibial nerve at varying intensities and paired‐pulse frequencies (0.07 Hz to 10 Hz). Results showed that maximal amplitude of the H‐reflex was reached at a similar intensity of stimulation in CON and HOT (p > 0.47), with a similar associated M‐wave (p > 0.69). However, maximal H‐reflex amplitude was significantly lower in HOT than CON (p < 0.05), whether expressed in absolute terms (‐50% in SOL, ‐32% in MG) or when normalized to the maximum M‐wave (‐23% in SOL, ‐32% in MG). The HPAD recovery curve was not affected by the elevated core temperature (p > 0.23). In summary, hyperthermia alters neuromuscular and Ia‐afferent pathway transmission, albeit the latter without an increase in HPAD.
The independent Influence of aerobic fitness and running economy on thermoregulation during running (1104.3)
Authors: Smoljanic Jovana , Dervis Sheila , Morris Nathan , Jay Ollie
Published: June 2021

This study assessed the independent influence of aerobic fitness (VO2max) and running economy (RE) on changes in esophageal (∆Tes) and rectal (∆Tre) temperatures, and whole body sweat losses (WBSL) during treadmill running. 5 unfit (UF: 45±3 mlO2•kg‐1•min‐1) and 5 fit (F: 61±5 mlO2•kg‐1•min‐1) males, matched for body mass (UF: 78.9±5.5 kg; F: 78.0±5.9 kg) ran at 1) a metabolic heat production (Hprod) of 640 W and 2) 60%VO2max. Also, 5 high RE (HI‐RE: 185±17 mlO2•kg‐1•km‐1) and 5 low RE (LO‐RE: 221±9 mlO2•kg‐1•km‐1) males, matched for mass and VO2max (HI‐RE: 73.8±7.2 kg, 60±4 mlO2•kg‐1•min‐1; LO‐RE: 73.5±6.9 kg, 61±7 mlO2•kg‐1•min‐1) ran at a 1) Hprod of 640 W and 2) fixed speed of 10.5 km•h‐1. Ambient conditions were 25.4±0.8°C, 37±12% RH. At 640 W, similar ∆Tes (F: 0.65±0.24°C; UF: 0.58±0.24°C), ∆Tre (F: 0.92±0.25°C; UF: 0.92±0.26°C), and WBSL (446±147 mL; HI: 528±52 mL) were observed irrespective of VO2max. At 60%VO2max, greater ∆Tes (F: 1.04±0.23°C; UF: 0.66±0.43°C), ∆Tre (F: 1.14±0.34°C; UF: 0.86±0.26°C) and WBSL (F: 859±152 mL; UF: 564±91 mL) were observed in the F group. At 10.5 km•h‐1, greater Hprod (LO‐RE: 992±109 W; HI‐RE: 822±107 W), ∆Tes (LO‐RE: 1.27±0.29°C; HI‐RE: 0.84±0.16°C), ∆Tre (LO‐RE: 1.49±0.29°C; HI‐RE: 0.96±0.34°C) and WBSL (LO‐RE: 861±57 mL; HI‐RE: 663±131 mL) were observed in the LO‐RE group. In conclusion, thermoregulatory responses are altered by RE due to differences in Hprod, but not VO2peak.

Grant Funding Source: Supported by NSERC (Dr. Ollie Jay ‐ Grant Holder)
Skin temperature responses following a warm‐weather road race (1104.4)
Authors: Belval Luke , Comstock Brett , Huggins Robert , Stearns Rebecca , Hosokawa Yuri , McKenzie Amy , Earp Jacob , Casa Douglas
Published: June 2021

Purpose: To quantify the skin temperature changes following intense exercise in warm‐weather. Methods: Anterior thermal images and gastrointestinal temperature (TGI) from 20 male runners (mean±SD; 73.5 ± 10.9 kg) participating in a 11.2 km road race were collected before and immediately after the race. Wet‐bulb globe temperature (WBGT) and wind speed were recorded at the finish line. Infrared thermal images were divided into 11 distinct regions, superior torso (ST), inferior torso (IT), face (F), right forearm (RF), left forearm (LF), right upper arm (RUA), left upper arm (LUA), right thigh (RT), left thigh (LT), right lower leg (RLL) and left lower leg (LLL). Mean weighted anterior skin temperature (MWST) was calculated via approximation of body surface area. Paired samples t‐tests were performed to compare pre‐ and post‐race values. Correlation analysis was performed to evaluate the relationship between MWST and TGI. Results: Mean WBGT was 27.04 ± 1.20 °C. Mean wind speed was 1.38 ± 0.87 km/h. TGI significantly increased from pre‐ to post‐race (pre: 37.18 ± 0.37 °C, post: 39.39 ± 0.73 °C, p<0.001). MWST decreased, approaching significance (pre: 30.46 ± 1.77 °C, post: 29.48 ± 0.95 °C, p=0.059). Mean skin temperature for ST (p=0.001), IT (p<0.001), RUA (p=0.015) and LUA (p=0.004) significantly decreased from pre‐race values. There was no relationship between Post‐TGI and Post‐MWST (r=0.052, p=0.848). Conclusions: Despite a significant increase in TGI, skin temperature decreased compared to pre‐race measures. ST, IT, RUA and LUA may represent the areas with the greatest potential for heat loss, given the air to skin temperature gradient.

Grant Funding Source: Supported by The Falmouth Road Race, The American Physiological Society and a UConn SURF Award
Effects of housing temperature on stress‐induced hyperthermia in mice, and the associated change in voluntary motor activity (1105.1)
Authors: Boily Patrice , Ring Daniel
Published: June 2021

Many studies that investigate stress‐induced hyperthermia (SIH) in rodents were conducted on mice housed under ambient temperatures (Ta) of 20‐22°C, which can induce chronic stress due to cold exposure. Further, SIH in mice is associated with an increase in voluntary motor activity (VMA). Given that VMA can be affected by Ta and that VMA can be a major source of heat production, we hypothesized that the amplitude of SIH, and the relationship between SIH and VMA, is affected by Ta. Two groups of 8 male mice, housed either at 21 or 27°C, were exposed to treatments known to induce varying levels of stress. For both groups. the treatments resulted The treatments for both groups resulted in an increasing SIH (control<handling<water spill<cage switch<clean cage) that was correlated to VMA; the slopes of the relationship between SIH and VMA did not differ between groups. The absolute amplitude of SIH of mice housed at 27ºC was significantly higher (by 0.45°C) than mice housed at 21°C, but the relative amplitude (during ‐ before stress) did not differ between groups. Within the range of Ta studied, we conclude that housing temperatures have minor effects on the stress response of mice.

Grant Funding Source: Supported by a CSU‐AAUP grant
Gender difference in thermal perception and the role of estrogen in mice (1105.3)
Authors: Nagasihma Kei , Marui Shuri , Tsunakawa Mizuki , Obata Chisa , Matsushita Haruka , Waki Naoya , Harada Hiroyoshi
Published: June 2021

The present study aimed to assess if there is a gender difference in thermal perception, and estrogen is involved in the mechanism. MethodsMale (M group) and female ICR mice were used (n=6 and 18, respectively). Each mouse was placed a device for temperature measurement in the abdominal cavity under general anesthesia. Female mice were divided to three groups: two groups were bilaterally ovariectomized with and without estradiol replacement (E2 and N groups) and one sham‐operated (F group). Mice were placed in an experiment box (50x12x15 cm), of which 5 Pertier boards at the bottom. Each board temperature was controlled by computer program, and changed each 6 min for 90 min. The temperature was selected from either of 28°C, 31°C, 34°C, 37°C, and 40°C with a difference from that of the other boards. Abdominal temperature (Tabd) and the position of a mouse and its board temperature were recorded every 1 min. Experiment was started after 60‐min baseline period with all boards set at 34°C. Mice were habituated to the box 2‐3 times before the experiment. ResultsDuring the housing period before the experiment, there were no differences in Tabd among the groups; however, during the experiment, Tabd was higher in the F group than in the M group. In addition, the F group preferred 40°C board, but the M group 34°C board. There were no differences in Tabd and temperature preference of the board among the F, E2 and N groups. Conclusion In this experimental condition, male mice showed higher environmental condition than female mice. However, estradiol is not likely mechanism for the difference.

Grant Funding Source: MEXT.KIBANKEISEI
Loss of SLN‐mediated thermogenesis is compensated by increased brown adipose tissue activity (1105.4)
Authors: Rowland Leslie , Bal Naresh , Periasamy Muthu
Published: June 2021

Thermogenic processes are critical contributors to body temperature maintenance and, when activated, are major components of metabolism. Elucidating the mechanisms that contribute to thermogenesis is of increasing importance as they can provide targets to combat the rising obesity epidemic. We recently identified Sarcolipin (SLN), a regulator of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) in skeletal muscle, as a significant contributor to metabolism and cold‐induced thermogenesis during an acute cold challenge. However, acute cold exposure does not allow for a detailed study of the physiological and molecular mechanisms involved. Thus, to further detail the role of SLN in thermogenesis, we challenged wild‐type (WT) and SLN‐knockout (SLN‐KO) mice to a long‐term cold exposure. SLN‐KO mice can adapt to gradual cold exposure and maintain normal core body temperature. However, SLN‐KO mice exhibit increased oxygen consumption compared to WT littermates and have greater physical activity and food intake. Histological examination of brown adipose (BAT) and inguinal fat depots showed increased depletion of fat stores from cold‐adapted SLN‐KO mice, and protein analysis showed increased UCP1 expression. These data show that SLN‐KO mice must significantly increase BAT activity and browning of white fat in order to compensate for the loss of SLN‐mediated thermogenesis. Increased physical activity, food intake, and elevated metabolic rate suggest a reliance on less efficient thermogenic mechanisms. Thus, an absence of SLN increases the energetic cost of survival in a cold environment. These data demonstrate that a combination of BAT and SLN‐based thermogenesis is necessary for survival in a cold environment and are integral components of energetic homeostasis.
Role of rat vascular KATP channels in setting microvascular oxygen pressure at the onset of contractions (1106.15)
Authors: Holdsworth Clark , Ferguson Scott , Wright Jennifer , Fees Alexander , Poole David , Musch Timothy
Published: June 2021

Effective blood‐muscle O2 flux demands a sufficient microvascular O2 driving pressure (PO2mv) which is set by the ratio of O2 delivery‐O2 utilization. Smooth muscle cell hyperpolarization contributes to exercise induced increases in skeletal muscle O2 delivery mediated, in part, by ATP‐sensitive K+ (KATP) channels. We hypothesized that KATP channel blockade via glibenclamide (GLI) would speed the fall of PO2mv following the onset of skeletal muscle contractions. Spinotrapezius PO2mv (phosphorescence quenching) was measured in 12 adult male Sprague Dawley rats at rest and during 180 s of 1 Hz twitch contractions (~7 V) under control (CON) and GLI (5 mg/kg) conditions. GLI increased mean arterial pressure (ΔCON: 2 ± 1, ΔGLI: 17 ± 4 mmHg, p < 0.05) and decreased heart rate (ΔCON: 3 ± 2, ΔGLI: ‐9 ± 3 bpm, p < 0.05) but did not change baseline PO2mv (CON: 34.0 ± 2.2, GLI: 33.7 ± 1.6 mmHg, p > 0.05). Following the onset of contractions the time constant, mean response time and contracting steady‐state PO2mv were not different between conditions (p > 0.05 for all). However, a clearly defined undershoot (p < 0.05) of the contracting steady‐state PO2mv was evident with GLI (8.0 ± 2.6 %) but not during CON (1.6 ± 1.1 %). Our data indicate that blockade of KATP channels does not impact PO2mv kinetics parameters during small muscle mass electrical stimulation, but can cause transient mismatch of O2 delivery‐O2 utilization prior to stabilizing at the contracting steady‐state PO2mv. This suggests that KATP channels contribute substantially to skeletal muscle microvascular function during the crucial rest to contraction transition and therefore have the potential to mediate skeletal muscle performance decrements evident in disease states.

Grant Funding Source: Supported by AHA Midwest Affiliate 0750090Z, NIH HL‐108328
Adenosine receptor activation influences postexercise skin blood flow (1106.20)
Authors: McGinn Ryan , Fujii Naoto , Kenny Glen
Published: June 2021

Adenosine receptor activation influences postexercise skin blood flow R. N. McGinn, N. Fujii, G. P. Kenny Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON, K1N 6N5 Studies show that postexercise skin blood flow (SkBF) is reduced despite persistent hyperthermia. We have ascribed this to altered active vasodilation rather than adrenergic vasoconstriction (Kenny, Front Bio 15:259 2010). However, recent work shows that adenosine receptors mediates the decrease in SkBF following passive heat stress (Swift et al, Exp Phys, Epub 2013), thus it is plausible that adenosine receptors may also modulate postexercise SkBF. Eight males cycled for 15 min (85% VO2max) and then rested for 60 min at 25°C. Four microdialysis probes were inserted in the forearm and infused with: a) Ringer’s Lactate (CON); b) L‐NAME (nitric oxide synthase inhibitor); c) bretylium tosylate (BT; sympathetic nerve transmission inhibitor) or d) theophylline (THEO; adenosine receptor inhibitor). Cutaneous vascular conductance (CVC) was calculated as SkBF divided by mean arterial pressure. End‐exercise CVC was similar at all sites except L‐NAME (18% lower, P<0.01). CVC returned to resting levels after 20 min of recovery in CON (P=0.11). Compared with CON, CVC was reduced at L‐NAME at 10 min of recovery (P=0.03) and was increased at BT for the first 30 min of recovery (P<0.05). However, THEO was elevated throughout recovery (P蠄0.01) compared to CON. We show recovery SkBF to be modulated by nitric oxide (10 min) and adrenergic vasoconstriction (30 min), but adenosine receptors exerts a more prolonged effect (60 min).

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Grant Funding Source: Supported by: Natural Sciences and Engineering Research Council of Canada