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1
Barreiro, Esther, Carlos Coronell, Barbara Laviña, Alba Ramírez-Sarmiento, Mauricio Orozco-Levi, and Joaquim Gea. "Aging, sex differences, and oxidative stress in human respiratory and limb muscles." Free Radical Biology and Medicine 41, no. 5 (September 2006): 797–809. http://dx.doi.org/10.1016/j.freeradbiomed.2006.05.027.
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Miotto, Paula M., Chris McGlory, Tanya M. Holloway, Stuart M. Phillips, and Graham P. Holloway. "Sex differences in mitochondrial respiratory function in human skeletal muscle." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 314, no. 6 (June 1, 2018): R909—R915. http://dx.doi.org/10.1152/ajpregu.00025.2018.
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Mitochondrial bioenergetic contributions to sex differences in human skeletal muscle metabolism remain poorly defined. The primary aim of this study was to determine whether mitochondrial respiratory kinetics differed between healthy young men and women in permeabilized skeletal muscle fibers. While men and women displayed similar ( P > 0.05) maximal respiration rates and abundance of mitochondrial/adenosine diphosphate (ADP) transport proteins, women had lower ( P < 0.05) mitochondrial ADP sensitivity (+30% apparent Km) and absolute respiration rates at a physiologically relevant ADP concentration (100 μM). Moreover, although men and women exhibited similar carnitine palmitoyl transferase-I protein content- and palmitoyl-CoA-supported respiration, women displayed greater sensitivity to malonyl-CoA-mediated respiratory inhibition. These data establish baseline sex differences in mitochondrial bioenergetics and provide the foundation for studying mitochondrial function within the context of metabolic perturbations and diseases that affect men and women differently.
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Dominelli, Paolo B., and Yannick Molgat-Seon. "Sex, gender and the pulmonary physiology of exercise." European Respiratory Review 31, no. 163 (January 12, 2022): 210074. http://dx.doi.org/10.1183/16000617.0074-2021.
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In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.
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Edmunds, Jane S., Clayton L. Ivie, Elizabeth P. Ott, Dain W. Jacob, Sarah E. Baker, Jennifer L. Harper, Camila M. Manrique-Acevedo, and Jacqueline K. Limberg. "Sex differences in the effect of acute intermittent hypoxia on respiratory modulation of sympathetic activity." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 321, no. 6 (December 1, 2021): R903—R911. http://dx.doi.org/10.1152/ajpregu.00042.2021.
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Sex-related differences in respiratory modulation of sympathetic activity have been observed in rodent models of sleep apnea [intermittent hypoxia (IH)]. In light of sex disparities in the respiratory response to acute IH in humans as well as changes in respiratory modulation of muscle sympathetic nerve activity (MSNA) in clinical sleep apnea, we examined sex-related differences in respiratory modulation of MSNA following acute IH. We hypothesized that respiratory modulation of MSNA would be altered in both male and female participants after IH; however, the respiratory patterning of MSNA following IH would be sex specific. Heart rate, MSNA, and respiration were evaluated in healthy male ( n = 21, 30 ± 5 yr) and female ( n = 10, 28 ± 5 yr) participants during normoxic rest before and after 30 min of IH. Respiratory modulation of MSNA was assessed by fitting polynomials to cross-correlation histograms constructed between sympathetic spikes and respiration. MSNA was elevated after IH in male (20 ± 6 to 24 ± 8 bursts/min) and female (19 ± 8 to 22 ± 10 bursts/min) participants ( P < 0.01). Both male and female participants exhibited respiratory modulation of MSNA ( P < 0.01); however, the pattern differed by sex. After IH, modulation of MSNA within the breath was reduced in male participants ( P = 0.03) but increased in female participants ( P = 0.02). Both male and female adults exhibit changes in respiratory patterning of MSNA after acute IH; however, this pattern differs by sex. These data support sex disparities in respiratory modulation of MSNA and may have implications for conditions such as sleep apnea.
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Guenette, Jordan A., Andrea M. Martens, Anne L. Lee, Gradin D. Tyler, Jennifer C. Richards, Glen E. Foster, Darren E. R. Warburton, and A. William Sheel. "Variable effects of respiratory muscle training on cycle exercise performance in men and women." Applied Physiology, Nutrition, and Metabolism 31, no. 2 (April 1, 2006): 159–66. http://dx.doi.org/10.1139/h05-016.
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Respiratory muscle training (RMT) has been proposed as an effective means to increase the strength of the inspiratory muscles and improve exercise performance. The purpose of this study was to examine the effect of RMT on cycling time to exhaustion (TTE) and to determine any potential sex effect. We hypothesized that RMT would improve maximal inspiratory pressure (MIP) and TTE to a similar degreee in men and women. Males (n = 7; mean (± SD) age, 22.1 ± 1.5 y) and females (n = 8; mean (± SD) 24.5 ± 4.9 y) performed an incremental cycle test to determine maximal oxygen consumption ([Formula: see text]O2 max) (day 1), followed by a familiarization TTE (day 2) and baseline TTE (day 3) at 80% maximal work achieved during the [Formula: see text]O2 max test. Subjects then completed 5 weeks of respiratory muscle training (RMT) (5 d/week, 2 sets of 30 inspirations against 50% MIP). Four training sessions per week were performed at home and the 5th was supervised, during which the threshold load was increased if necessary. Following RMT, subjects completed 2 TTE tests (days 4 and 5). MIP increased in each subject (37% ± 18%, P < 0.05). There was no difference between men (pre = -100 ± 20 vs. post = -140 ± 29 cmH2O) and women (pre = -90 ± 28 vs. post = -117 ± 28 cmH2O). Baseline TTE (male = 301 ± 122 s; female = 338 ± 98 s) was shorter in comparison with the best of the 2 TTE-post tests (male = 353 ± 68 s; female = 416 ± 116 s; P < 0.01), but not when compared with days 4 or 5 (P > 0.05). RMT increases MIP and may improve exercise performance; however, improvements are variable with no differences between men and women.Key words: constant-intensity exercise, dyspnea, factors limiting exercise, maximal inspiratory pressure, respiratory muscles.
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Chen, H. I., and C. S. Kuo. "Relationship between respiratory muscle function and age, sex, and other factors." Journal of Applied Physiology 66, no. 2 (February 1, 1989): 943–48. http://dx.doi.org/10.1152/jappl.1989.66.2.943.
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To investigate the effects of gender and age on respiratory muscle function, 160 healthy volunteers (80 males, 80 females) were divided into four age groups. Twenty-eight of the male subjects were smokers. After the subjects were familiarized with the experimental procedure, respiratory muscle strength, inspiratory muscle endurance, and spirometric function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, tidal volume, breathing rate, and duty cycle, were measured. The respiratory muscle strength was indicated by the maximal static inspiratory and expiratory pressures (PImmax and PEmmax). Inspiratory muscle endurance was determined by the time the subject was able to sustain breathing against an inspiratory pressure load on a modified Nickerson-Keens device. The results showed that 1) except for inspiratory muscle endurance and FEV1/FVC, men had greater respiratory muscle and pulmonary functions than women, 2) respiratory muscle function and pulmonary function decreased with age, 3) smoking tended to lower duty cycle and FEV1/FVC and to enhance PE,mmax, and 4) inspiratory muscle endurance was greater in men who were physically active than in those who were sedentary. Therefore we conclude that there are sexual and age differences in respiratory muscle strength and pulmonary function and that smoking or physical activity may affect respiratory muscle function.
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Kalidhindi, Rama Satyanarayana Raju, Niyati A. Borkar, Nilesh Sudhakar Ambhore, Christina M. Pabelick, Y. S. Prakash, and Venkatachalem Sathish. "Sex steroids skew ACE2 expression in human airway: a contributing factor to sex differences in COVID-19?" American Journal of Physiology-Lung Cellular and Molecular Physiology 319, no. 5 (November 1, 2020): L843—L847. http://dx.doi.org/10.1152/ajplung.00391.2020.
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The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males versus females as a model, we explored the effect of estrogen versus testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared with males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
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Ofir, Dror, Pierantonio Laveneziana, Katherine A. Webb, Yuk-Miu Lam, and Denis E. O'Donnell. "Sex differences in the perceived intensity of breathlessness during exercise with advancing age." Journal of Applied Physiology 104, no. 6 (June 2008): 1583–93. http://dx.doi.org/10.1152/japplphysiol.00079.2008.
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The prevalence of activity-related breathlessness increases with age, particularly in women, but the specific underlying mechanisms have not been studied. This novel cross-sectional study was undertaken to examine the effects of age and sex, and their interaction, on the perceptual and ventilatory responses to incremental treadmill exercise in 73 healthy participants (age range 40–80 yr old) with normal pulmonary function. Age-related changes at a standardized oxygen uptake (V̇o2) during exercise included significant increases in breathlessness ratings (Borg scale), ventilation (V̇e), ventilatory equivalent for carbon dioxide, and the ratio of tidal volume (Vt) to dynamic inspiratory capacity (IC) (all P < 0.05). These changes were quantitatively similar in women ( n = 39) and in men ( n = 34). For the group as a whole, exertional breathlessness ratings increased as resting static inspiratory muscle strength diminished ( P = 0.05), as exercise ventilation increased relative to capacity ( P = 0.013) and as the Vt/IC ratio increased ( P = 0.003) during exercise. Older women (60–80 yr old, n = 23) reported greater ( P < 0.05) intensity of exertional breathlessness at a standardized V̇o2 and V̇e than age-matched men ( n = 16), despite similar age-related changes in ventilatory demand and dynamic ventilatory mechanics. These increases in breathlessness ratings in older women disappeared when sex differences in baseline maximal ventilatory capacity were accounted for. In conclusion, although increased exertional breathlessness with advancing age is multifactorial, contributory factors included higher ventilatory requirements during exercise, progressive inspiratory muscle weakness, and restrictive mechanical constraints on Vt expansion related to reduced IC. The sensory consequences of this age-related respiratory impairment were more pronounced in women, who, by nature, have relatively reduced maximal ventilatory reserve.
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Murias, Juan M., Daniel A. Keir, Matthew D. Spencer, and Donald H. Paterson. "Sex-related differences in muscle deoxygenation during ramp incremental exercise." Respiratory Physiology & Neurobiology 189, no. 3 (December 2013): 530–36. http://dx.doi.org/10.1016/j.resp.2013.08.011.
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Tarnopolsky, Mark A. "Gender Differences in Substrate Metabolism During Endurance Exercise." Canadian Journal of Applied Physiology 25, no. 4 (August 1, 2000): 312–27. http://dx.doi.org/10.1139/h00-024.
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Females show a lower respiratory exchange ratio (RER) than males during submaximal endurance exercise, which translates into a proportionately lower carbohydrate and higher fat oxidation. Data from rodents show that 17-β-estradiol may mediate these metabolic differences. 17-β-estradiol supplementation in humans is less convincing; however, two studies found a reduction in glucose rate of appearance during exercise. No difference is found between genders in muscle glycogen content; however, lipid content in muscle is higher in females. Evidence shows that short chain OH-acyl CoA-dehydrogenase (SCHAD) maximal enzyme activity is higher in females. The rate of leucine oxidation is lower in females at rest and during endurance exercise. This is not apparently related to gender differences in branched chain-2-oxo-dehydrogenase (BCOAD) activity in skeletal muscle, which may implicate hepatic control. Important muscle proteins to examine in future research are hormone sensitive lipase, the enzymes of β-oxidation, and fatty acid transporters. Key words: estradiol, progesterone, testosterone, sex differences, substrate metabolism, muscle enzymes
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Malone, Ian G., Rachel L. Nosacka, Marissa A. Nash, Kevin J. Otto, and Erica A. Dale. "Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury." Journal of Neurophysiology 126, no. 2 (August 1, 2021): 607–26. http://dx.doi.org/10.1152/jn.00625.2020.
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Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function, with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore the rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity, including a brief examination of sex-related differences in these mechanisms. Finally, we suggest that more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.
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Horton, Tracy J., S. Renee Commerford, Michael J. Pagliassotti, and Daniel H. Bessesen. "Postprandial leg uptake of triglyceride is greater in women than in men." American Journal of Physiology-Endocrinology and Metabolism 283, no. 6 (December 1, 2002): E1192—E1202. http://dx.doi.org/10.1152/ajpendo.00164.2002.
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The postprandial excursion of plasma triglyceride (TG) concentration is greater in men than in women. In this study, the disposition of dietary fat was examined in lean healthy men and women ( n = 8/group) in either the overnight-fasted or fed (4.5 h after breakfast) states. A [14C]oleate tracer was incorporated into a test meal, providing 30% of total daily energy requirements. After ingestion of the test meal, measures of arteriovenous differences in TG and14C across the leg were combined with needle biopsies of skeletal muscle and adipose tissue and respiratory gas collections to define the role of skeletal muscle in the clearance of dietary fat. The postprandial plasma TG and14C tracer excursions were lower ( P = 0.04) in women than in men in the overnight-fasted and fed states. Women, however, had significantly greater limb uptake of total TG compared with men on both the fasted (3,849 ± 846 vs. 528 ± 221 total μmol over 6 h) and fed (4,847 ± 979 vs. 1,571 ± 334 total μmol over 6 h) days. This was also true for meal-derived14C lipid uptake.14C content of skeletal muscle tissue (μCi/g tissue) was significantly greater in women than in men 6 h after ingestion of the test meal. In contrast,14C content of adipose tissue was not significantly different between men and women at 6 h. The main effect of nutritional state, fed vs. fasted, was to increase the postmeal glucose ( P = 0.01) excursion (increase from baseline) and decrease the postmeal TG excursion ( P = 0.02). These results support the notion that enhanced skeletal muscle clearance of lipoprotein TG in women contributes to their reduced postprandial TG excursion. Questions remain as to the mechanisms causing these sex-based differences in skeletal muscle TG uptake and metabolism. Furthermore, nutritional state can significantly impact postprandial metabolism in both men and women.
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Sheel, A. William, Jennifer C. Richards, Glen E. Foster, and Jordan A. Guenette. "Sex Differences in Respiratory Exercise Physiology." Sports Medicine 34, no. 9 (2004): 567–79. http://dx.doi.org/10.2165/00007256-200434090-00002.
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Carlo, W. A., and J. M. DiFiore. "Respiratory muscle responses to changes in chemoreceptor drive in infants." Journal of Applied Physiology 68, no. 3 (March 1, 1990): 1041–47. http://dx.doi.org/10.1152/jappl.1990.68.3.1041.
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Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea.
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Hunter, Sandra K., Ashley Critchlow, and Roger M. Enoka. "Influence of aging on sex differences in muscle fatigability." Journal of Applied Physiology 97, no. 5 (November 2004): 1723–32. http://dx.doi.org/10.1152/japplphysiol.00460.2004.
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The purpose of this study was to compare time to task failure for a sustained isometric contraction performed at a submaximal intensity with elbow flexor muscles by young and old men and women. Twenty-seven young (14 men and 13 women, 18–35 yr) and 18 old (10 men and 8 women, 65–80 yr) adults sustained an isometric contraction at 20% of maximal voluntary contraction torque until target torque could no longer be achieved for ≥5 s. Young adults were stronger than old adults (66.8 ± 17.9 vs. 47.7 ± 18.1 N·m, P < 0.05), and men were stronger than women (69.8 ± 17.9 vs. 47.1 ± 15.3 N·m, P < 0.05), with no interaction between age and sex ( P > 0.05). Time to task failure was longer for old than for young adults (22.8 ± 9.1 vs. 14.4 ± 7.6 min, P < 0.05) and for young women than for young men (18.3 ± 8.0 vs. 10.8 ± 5.2, P < 0.05), but there was no difference between old women and men (21.3 ± 10.7 and 24.1 ± 8.0 min, respectively, P > 0.05) or between young women and old adults ( P > 0.05). Mean arterial pressure, heart rate, average electromyographic (EMG) activity, and torque fluctuations of elbow flexor muscles increased during the fatiguing contraction ( P < 0.05) for all subjects. Rates of increase in mean arterial pressure, heart rate, and torque fluctuations were greater for young men and old adults, with no differences between old men and women ( P > 0.05). Similarly, the rate of increase in EMG activity was greater for young men than for the other three groups. EMG bursts were less frequent for old adults ( P < 0.05) at the end of the fatiguing contraction, and this was accompanied by reduced fluctuations in torque. Consequently, time to task failure was related to target torque for young, but not old, adults, and differences in task duration were accompanied by parallel changes in the pressor response.
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SCHULZ, H., C. JOHNER, G. EDER, A. ZIESENIS, P. REITMEIER, J. HEYDER, and R. BALLING. "Respiratory mechanics in mice: strain and sex specific differences." Acta Physiologica Scandinavica 174, no. 4 (April 2002): 367–75. http://dx.doi.org/10.1046/j.1365-201x.2002.00955.x.
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Watanabe, Daiki, Koji Hatakeyama, Ryo Ikegami, Hiroaki Eshima, Kazuyoshi Yagishita, David C. Poole, and Yutaka Kano. "Sex differences in mitochondrial Ca2+ handling in mouse fast-twitch skeletal muscle in vivo." Journal of Applied Physiology 128, no. 2 (February 1, 2020): 241–51. http://dx.doi.org/10.1152/japplphysiol.00230.2019.
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We investigated sex differences in mitochondrial Ca2+ handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca2+ concentration ([Ca2+]cyto) were measured in vivo using tibialis anterior muscles from male and female mice. The muscles were exposed to increasing concentrations of cyclopiazonic acid [CPA; sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitor] (from 10 to 30 to 50 μM at 10 min intervals). Thirty minutes after treatment, [Ca2+]cyto was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca2+]cyto in male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca2+ uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca2+]cyto increase. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared with males (mitochondria number: 13.1 ± 1.0 in males vs. 19.9 ± 2.3 in females; mitochondrial volume: 0.034 ± 0.004 μm3/μm3 fiber volume in males vs. 0.066 ± 0.008 μm3/μm3 fiber volume in females, both P < 0.05). There were no sex differences in the content of SR Ca2+-ATPase, mitochondrial Ca2+ uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that 1) mitochondrial Ca2+ uptake ability is greater in female than male myocytes, and 2) this superior Ca2+ uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content but not to the expression of mitochondrial proteins related to mitochondrial Ca2+ uptake. NEW & NOTEWORTHY This investigation presents evidence that female versus male fast-twitch muscle exhibits a greater mitochondrial calcium ion uptake capability that is partly conferred by the higher intermyofibrillar mitochondrial volume density.
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De Troyer, André, Peter A. Kirkwood, and Theodore A. Wilson. "Respiratory Action of the Intercostal Muscles." Physiological Reviews 85, no. 2 (April 2005): 717–56. http://dx.doi.org/10.1152/physrev.00007.2004.
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The mechanical advantages of the external and internal intercostals depend partly on the orientation of the muscle but mostly on interspace number and the position of the muscle within each interspace. Thus the external intercostals in the dorsal portion of the rostral interspaces have a large inspiratory mechanical advantage, but this advantage decreases ventrally and caudally such that in the ventral portion of the caudal interspaces, it is reversed into an expiratory mechanical advantage. The internal interosseous intercostals in the caudal interspaces also have a large expiratory mechanical advantage, but this advantage decreases cranially and, for the upper interspaces, ventrally as well. The intercartilaginous portion of the internal intercostals (the so-called parasternal intercostals), therefore, has an inspiratory mechanical advantage, whereas the triangularis sterni has a large expiratory mechanical advantage. These rostrocaudal gradients result from the nonuniform coupling between rib displacement and lung expansion, and the dorsoventral gradients result from the three-dimensional configuration of the rib cage. Such topographic differences in mechanical advantage imply that the functions of the muscles during breathing are largely determined by the topographic distributions of neural drive. The distributions of inspiratory and expiratory activity among the muscles are strikingly similar to the distributions of inspiratory and expiratory mechanical advantages, respectively. As a result, the external intercostals and the parasternal intercostals have an inspiratory function during breathing, whereas the internal interosseous intercostals and the triangularis sterni have an expiratory function.
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DiMarco, A. F., J. R. Romaniuk, and G. S. Supinski. "Parasternal and external intercostal responses to various respiratory maneuvers." Journal of Applied Physiology 73, no. 3 (September 1, 1992): 979–86. http://dx.doi.org/10.1152/jappl.1992.73.3.979.
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Recent studies suggest that the external intercostal (EI) muscles of the upper rib cage, like the parasternals (PA), play an important ventilatory role, even during eupneic breathing. The purpose of the present study was to further assess the ventilatory role of the EI muscles by determining their response to various static and dynamic respiratory maneuvers and comparing them with the better-studied PA muscles. Applied interventions included 1) passive inflation and deflation, 2) abdominal compression, 3) progressive hypercapnia, and 4) response to bilateral cervical phrenicotomy. Studies were performed in 11 mongrel dogs. Electromyographic (EMG) activities were monitored via bipolar stainless steel electrodes. Muscle length (percentage of resting length) was monitored with piezoelectric crystals. With passive rib cage inflation produced either with a volume syringe or abdominal compression, each muscle shortened; with passive deflation, each muscle lengthened. During eupneic breathing, each muscle was electrically active and shortened to a similar degree. In response to progressive hypercapnia, peak EMG of each intercostal muscle increased linearly and to a similar extent. Inspiratory shortening also increased progressively with increasing PCO2, but in a curvilinear fashion with no significant differences in response among intercostal muscles. In response to phrenicotomy, the EMG and degree of inspiratory shortening of each intercostal muscle increased significantly. Again, the response among intercostal muscles was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
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Dempsey, Jerome A., Andre La Gerche, and James H. Hull. "Is the healthy respiratory system built just right, overbuilt, or underbuilt to meet the demands imposed by exercise?" Journal of Applied Physiology 129, no. 6 (December 1, 2020): 1235–56. http://dx.doi.org/10.1152/japplphysiol.00444.2020.
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In the healthy, untrained young adult, a case is made for a respiratory system (airways, pulmonary vasculature, lung parenchyma, respiratory muscles, and neural ventilatory control system) that is near ideally designed to ensure a highly efficient, homeostatic response to exercise of varying intensities and durations. Our aim was then to consider circumstances in which the intra/extrathoracic airways, pulmonary vasculature, respiratory muscles, and/or blood-gas distribution are underbuilt or inadequately regulated relative to the demands imposed by the cardiovascular system. In these instances, the respiratory system presents a significant limitation to O2 transport and contributes to the occurrence of locomotor muscle fatigue, inhibition of central locomotor output, and exercise performance. Most prominent in these examples of an “underbuilt” respiratory system are highly trained endurance athletes, with additional influences of sex, aging, hypoxic environments, and the highly inbred equine. We summarize by evaluating the relative influences of these respiratory system limitations on exercise performance and their impact on pathophysiology and provide recommendations for future investigation.
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Bailey, E. F., and R. F. Fregosi. "Coordination of intrinsic and extrinsic tongue muscles during spontaneous breathing in the rat." Journal of Applied Physiology 96, no. 2 (February 2004): 440–49. http://dx.doi.org/10.1152/japplphysiol.00733.2003.
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The muscular-hydrostat model of tongue function proposes a constant interaction of extrinsic (external bony attachment, insertion into base of tongue) and intrinsic (origin and insertion within the tongue) tongue muscles in all tongue movements (Kier WM and Smith KK. Zool J Linn Soc 83: 207-324, 1985). Yet, research that examines the respiratory-related effects of tongue function in mammals continues to focus almost exclusively on the respiratory control and function of the extrinsic tongue protrusor muscle, the genioglossus muscle. The respiratory control and function of the intrinsic tongue muscles are unknown. Our purpose was to determine whether intrinsic tongue muscles have a respiration-related activity pattern and whether intrinsic tongue muscles are coactivated with extrinsic tongue muscles in response to respiratory-related sensory stimuli. Esophageal pressure and electromyographic (EMG) activity of an extrinsic tongue muscle (hyoglossus), an intrinsic tongue muscle (superior longitudinal), and an external intercostal muscle were studied in anesthetized, tracheotomized, spontaneously breathing rats. Mean inspiratory EMG activity was compared at five levels of inspired CO2. Intrinsic tongue muscles were often quiescent during eupnea but active during hypercapnia, whereas extrinsic tongue muscles were active in both eupnea and hypercapnia. During hypercapnia, the activities of the airway muscles were largely coincident, although the onset of extrinsic muscle activity generally preceded the onset of intrinsic muscle activation. Our findings provide evidence, in an in vivo rodent preparation, of respiratory modulation of motoneurons supplying intrinsic tongue muscles. Distinctions noted between intrinsic and extrinsic activities could be due to differences in motoneuron properties or the central, respiration-related control of each motoneuron population.
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Hunter, Sandra K., and Roger M. Enoka. "Sex differences in the fatigability of arm muscles depends on absolute force during isometric contractions." Journal of Applied Physiology 91, no. 6 (December 1, 2001): 2686–94. http://dx.doi.org/10.1152/jappl.2001.91.6.2686.
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Women are capable of longer endurance times compared with men for contractions performed at low to moderate intensities. The purpose of the study was 1) to determine the relation between the absolute target force and endurance time for a submaximal isometric contraction and 2) to compare the pressor response and muscle activation patterns of men [26.3 ± 1.1 (SE) yr] and women (27.5 ± 2.3 yr) during a fatiguing contraction performed with the elbow flexor muscles. Maximal voluntary contraction (MVC) force was greater for men (393 ± 23 vs. 177 ± 7 N), which meant that the average target force (20% of MVC) was greater for men (79.7 ± 6.5 vs. 36.7 ± 2.0 N). The endurance time for the fatiguing contractions was 118% longer for women (1,806 ± 239 vs. 829 ± 94 s). The average of the rectified electromyogram (%MVC) for the elbow flexor muscles at exhaustion was similar for men (31 ± 2%) and women (30 ± 2%). In contrast, the heart rate and mean arterial pressure (MAP) were less at exhaustion for women (94 ± 6 vs. 111 ± 7 beats/min and 121 ± 5 vs. 150 ± 6 mmHg, respectively). The target force and change in MAP during the fatiguing contraction were exponentially related to endurance time ( r 2 = 0.68 and r 2 = 0.64, respectively), whereas the change in MAP was linearly related to target force ( r 2 = 0.51). The difference in fatigability of men and women when performing a submaximal contraction was related to the absolute contraction intensity and was limited by mechanisms that were distal to the activation of muscle.
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Dick, T. E., and E. van Lunteren. "Fiber subtype distribution of pharyngeal dilator muscles and diaphragm in the cat." Journal of Applied Physiology 68, no. 5 (May 1, 1990): 2237–40. http://dx.doi.org/10.1152/jappl.1990.68.5.2237.
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In previous studies differences were frequently found between the pharyngeal dilator muscles and the thoracic respiratory muscles in their patterns of electrical and mechanical activity during the respiratory cycle, with both resting and stimulated breathing. However, little is known about the intrinsic properties of the pharyngeal muscles and how they relate to the intrinsic properties of the diaphragm. In the present study, the fiber subtype distributions of two pharyngeal dilator muscles, the geniohyoid and the sternohyoid, were ascertained histochemically in the cat. The geniohyoid and the sternohyoid muscles had a preponderance of fast glycolytic (FG) fibers (mean 48 and 55%, respectively), a smaller number of fast oxidative-glycolytic (FOG) fibers (mean 36 and 31%, respectively), and few slow oxidative (SO) fibers (mean 16 and 14%, respectively). The percentages of SO fibers of both hyoid muscles were significantly (P less than 0.01) lower than that of the costal diaphragm, and the percentages of FOG and FG fibers were significantly higher than that of the diaphragm. In conclusion, the geniohyoid and sternohyoid muscles have histochemical characteristics usually associated with fast contraction and intermediate endurance properties.
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Katagiri, M., R. N. Young, R. S. Platt, T. M. Kieser, and P. A. Easton. "Respiratory muscle compensation for unilateral or bilateral hemidiaphragm paralysis in awake canines." Journal of Applied Physiology 77, no. 4 (October 1, 1994): 1972–82. http://dx.doi.org/10.1152/jappl.1994.77.4.1972.
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In humans and some animals, the surviving respiratory muscles are able to compensate fully for unilateral, and partially for bilateral, hemidiaphragm paralysis. To examine differential activity of individual respiratory muscles after unilateral or bilateral diaphragm paralysis, length and electromyogram (EMG) of left costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis were measured directly in five awake canines after implantation with sonomicrometry transducers and bipolar EMG electrodes under three conditions: during normal breathing (NOFRZ), after infusion of local anesthetic (bupivacaine) through a cervical phrenic nerve cuff to induce reversible contralateral hemidiaphragm (CNFRZ), and after bilateral diaphragm (BIFRZ) paralysis. From NOFRZ to CNFRZ, costal, crural, parasternal, and transversus abdominis increased shortening and EMG activity to compensate for contralateral diaphragm paralysis, but the increase in activity was not equivalent for each muscle. With BIFRZ, parasternal and transversus abdominis showed further increases in activity, coordinated between both inspiration and expiration. Normalized intrabreath profiles revealed dynamic differences in development of muscle activity within each breath as paralysis worsened. Review of simultaneous muscle activities showed coordinated interactions among the compensating muscles: passive shortening of transversus, and lengthening of costal and crural, coincided with increased active inspiratory shortening of parasternal. We conclude that an integrated strategy of respiratory muscle compensation for unilateral or bilateral diaphragm paralysis occurs among chest wall, abdominal, and diaphragm segmental muscles, with relative contributions of individual muscles adjusted according to the degree of diaphragm dysfunction.
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Aljuraifani, Rafeef, Ryan E. Stafford, Leanne M. Hall, Wolbert van den Hoorn, and Paul W. Hodges. "Task-specific differences in respiration-related activation of deep and superficial pelvic floor muscles." Journal of Applied Physiology 126, no. 5 (May 1, 2019): 1343–51. http://dx.doi.org/10.1152/japplphysiol.00704.2018.
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The female pelvic floor muscles (PFM) are arranged in distinct superficial and deep layers that function to support the pelvic/abdominal organs and maintain continence, but with some potential differences in function. Although general recordings of PFM activity show amplitude modulation in conjunction with fluctuation in intra-abdominal pressure such as that associated with respiration, it is unclear whether the activities of the two PFM layers modulate in a similar manner. This study aimed to investigate the activation of the deep and superficial PFM during a range of respiratory tasks in different postures. Twelve women without pelvic floor dysfunction participated. A custom-built surface electromyography (EMG) electrode was used to record the activation of the superficial and deep PFM during quiet breathing, breathing with increased dead space, coughing, and maximal and submaximal inspiratory and expiratory efforts. As breathing demand increased, the deep PFM layer EMG had greater coherence with respiratory airflow at the frequency of respiration than the superficial PFM ( P = 0.038). During cough, the superficial PFM activated earlier than the deep PFM in the sitting position ( P = 0.043). In contrast, during maximal and submaximal inspiratory and expiratory efforts, the superficial PFM EMG was greater than that for the deep PFM ( P = 0.011). These data show that both layers of PFM are activated during both inspiration and expiration, but with a bias to greater activation in expiratory tasks/phases. Activation of the deep and superficial PFM layers differed in most of the respiratory tasks, but there was no consistent bias to one muscle layer.NEW & NOTEWORTHY Although pelvic floor muscles are generally considered as a single entity, deep and superficial layers have different anatomies and biomechanics. Here we show task-specific differences in recruitment between layers during respiratory tasks in women. The deep layer was more tightly modulated with respiration than the superficial layer, but activation of the superficial layer was greater during maximal/submaximal occluded respiratory efforts and earlier during cough. These data highlight tightly coordinated recruitment of discrete pelvic floor muscles for respiration.
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Hershenson, M. B., Y. Kikuchi, and S. H. Loring. "Relative strengths of the chest wall muscles." Journal of Applied Physiology 65, no. 2 (August 1, 1988): 852–62. http://dx.doi.org/10.1152/jappl.1988.65.2.852.
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We hypothesized that during maximal respiratory efforts involving the simultaneous activation of two or more chest wall muscles (or muscle groups), differences in muscle strength require that the activity of the stronger muscle be submaximal to prevent changes in thoracoabdominal configuration. Furthermore we predicted that maximal respiratory pressures are limited by the strength of the weaker muscle involved. To test these hypotheses, we measured the pleural pressure, abdominal pressure (Pab), and transdiaphragmatic pressure (Pdi) generated during maximal inspiratory, open-glottis and closed-glottis expulsive, and combined inspiratory and expulsive maneuvers in four adults. We then determined the activation of the diaphragm and abdominal muscles during selected maximal respiratory maneuvers, using electromyography and phrenic nerve stimulation. In all subjects, the Pdi generated during maximal inspiratory efforts was significantly lower than the Pdi generated during open-glottis expulsive or combined efforts, suggesting that rib cage, not diaphragm, strength limits maximal inspiratory pressure. Similarly, at high lung volumes, the Pab generated during closed-glottis expulsive efforts was significantly greater than that generated during open-glottis efforts, suggesting that the latter pressure is limited by diaphragm, not abdominal muscle, strength. As predicted, diaphragm activation was submaximal during maximal inspiratory efforts, and abdominal muscle activation was submaximal during open-glottis expulsive efforts at midlung volume. Additionally, assisting the inspiratory muscles of the rib cage with negative body-surface pressure significantly increased maximal inspiratory pressure, whereas loading the rib cage muscles with rib cage compression decreased maximal inspiratory pressure. We conclude that activation of the chest wall muscles during static respiratory efforts is determined by the relative strengths and mechanical advantage of the muscles involved.
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Jennings, Donald B. "Respiratory Control During Exercise: Hormones, Osmolality, Strong Ions, and Paco2." Canadian Journal of Applied Physiology 19, no. 3 (September 1, 1994): 334–49. http://dx.doi.org/10.1139/h94-027.
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For optimal performance of exercising muscle, the charge state of proteins must be maintained; the pH environment of protein histidine imidazole groups must be coordinated with their pK. During exercise, increasing temperature and osmolality as well as changes in strong ions affect the pK of imidazole groups. Production of strong organic anions also decreases the concentration difference between strong cations and anions (strong ion difference, or [SID]), causing a metabolic acidosis in peripheral tissues. Central chemoreceptors regulate [Formula: see text] in relation to the [SID] of brain fluids to maintain a "constant" brain [H+]. In addition, increased osmolality, angiotensin II, and vasopressin during exercise may stimulate circumventricular organs of the brain and interact with chemical control of ventilation. Changes in [SID] of brain fluids during exercise are negligible compared to systemic decreases in [SID]; thus, regulation of [Formula: see text] to maintain brain [H+] homeostasis cannot simultaneously compensate for greater changes in [SID] in peripheral tissues. Key words: circumventricular organs, central chemoreception, angiotensin II, vasopressin, alphastat theory
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Saito, M., T. Mano, S. Iwase, K. Koga, H. Abe, and Y. Yamazaki. "Responses in muscle sympathetic activity to acute hypoxia in humans." Journal of Applied Physiology 65, no. 4 (October 1, 1988): 1548–52. http://dx.doi.org/10.1152/jappl.1988.65.4.1548.
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Responses in muscle sympathetic activity (MSA) to acute hypoxia were studied in 13 healthy male subjects under hypobaric hypoxic conditions at a simulated altitude of 4,000, 5,000, and 6,000 m. Efferent postganglionic MSA was recorded directly with a tungsten microelectrode inserted percutaneously into the tibial nerve. Heart rate (HR) and respiratory rate (RR) were counted respectively from the R wave of an electrocardiogram and from the respiratory tracing recorded by the strain-gauge method. The average values of the MSA burst rate and total activity of MSA (burst rate x mean burst amplitude) at 4,000, 5,000, and 6,000 m were 36.4 +/- 2.6, 39.1 +/- 3.1, and 40.2 +/- 4.2 (SE) bursts/min and 616 +/- 138, 794 +/- 190, and 764 +/- 227 arbitrary units, respectively. These values were significantly higher than the values of 27.1 +/- 2.9 bursts/min and 446 +/- 28 at sea level. HR increased significantly at altitudes, but RR did not show significant change. Under severe hypoxic conditions beyond 5,000 m, there were large interindividual differences in the MSA responsiveness to hypoxia. The results indicate that MSA is activated under hypoxia by stimulating the chemoreceptors. However, the central controlling mechanisms that would be affected by hypoxia may also influence the MSA responsiveness under severe hypoxia.
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Park, Song-Young, Matthew J. Rossman, Jayson R. Gifford, Leena P. Bharath, Johann Bauersachs, Russell S. Richardson, E. Dale Abel, J. David Symons, and Christian Riehle. "Exercise training improves vascular mitochondrial function." American Journal of Physiology-Heart and Circulatory Physiology 310, no. 7 (April 1, 2016): H821—H829. http://dx.doi.org/10.1152/ajpheart.00751.2015.
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Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-γ coactivator-1α and the downstream targets cytochrome c oxidase subunit IV isoform 1, isocitrate dehydrogenase ( Idh) 2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser1177), and suppressed reactive oxygen species generation (all P < 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function.
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Rozand, Vianney, Jonathon W. Senefeld, Christopher W. Sundberg, Ashleigh E. Smith, and Sandra K. Hunter. "Differential effects of aging and physical activity on corticospinal excitability of upper and lower limb muscles." Journal of Neurophysiology 122, no. 1 (July 1, 2019): 241–50. http://dx.doi.org/10.1152/jn.00077.2019.
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Corticospinal tract excitability can be altered by age, physical activity (PA), and possibly sex, but whether these effects differ between upper and lower limb muscles is unknown. We determined the influence of age, PA, and sex on corticospinal excitability of an upper limb and a lower limb muscle during submaximal contractions by comparing stimulus-response curves of motor evoked potentials (MEPs). Transcranial magnetic stimulation (TMS) was used to evoke stimulus-response curves in active muscles by incrementally increasing the stimulator intensity from below the active motor threshold (AMT) until a plateau in MEP amplitudes was achieved. Stimulus-response curves were analyzed from the first dorsal interosseous (FDI) of 30 young (23.9 ± 3.8 yr) and 33 older (72.6 ± 5.6 yr) men and women and the vastus lateralis (VL) of 13 young (23.2 ± 2.2 yr) and 25 older (72.7 ± 5.5 yr) men and women. Corticospinal excitability was determined by fitting the curves with a four-parameter sigmoidal curve and calculating the maximal slope (slopemax). PA was assessed with triaxial accelerometry, and participants were dichotomized into high-PA (>10,000 steps/day, n = 15) or low-PA (<10,000 steps/day, n = 43) groups. Young adults had larger FDI MEP amplitudes (% maximum amplitude of compound muscle action potential) at higher TMS intensities (120–150% AMT) and greater slopemax than older adults ( P < 0.05), with no differences between high- and low-PA groups ( P > 0.05). VL MEP amplitudes and slopemax, however, were lower in the high-PA than low-PA participants, with no age or sex differences. These data suggest that aging and PA, but not sex, differentially influence the excitability of the corticospinal tracts projecting to muscles of the upper compared with the lower limb. NEW & NOTEWORTHY Excitability of the corticospinal tract projecting to the first dorsal interosseous assessed with transcranial magnetic stimulation was reduced with age but independent of regular physical activity (steps/day) and sex of the individual. In contrast, corticospinal excitability of the vastus lateralis was not affected by age but was reduced in individuals achieving more than the physical activity recommendations of 10,000 steps/day. Aging and activity differentially affect corticospinal excitability of upper and lower limb muscles.
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Salminen, A., P. Saari, and M. Kihlström. "Age- and sex-related differences in lipid peroxidation of mouse cardiac and skeletal muscles." Comparative Biochemistry and Physiology Part B: Comparative Biochemistry 89, no. 4 (January 1988): 695–99. http://dx.doi.org/10.1016/0305-0491(88)90310-0.
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Shephard, R. J., E. Bouhlel, H. Vandewalle, and H. Monod. "Muscle mass as a factor limiting physical work." Journal of Applied Physiology 64, no. 4 (April 1, 1988): 1472–79. http://dx.doi.org/10.1152/jappl.1988.64.4.1472.
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Maximal exercise has been performed by eight men and eight women, using four types of ergometer (2-leg, 1-leg, arm + shoulder, and arm) while breathing room air and while breathing 12% O2. Results have been related to anthropometric estimates of muscle mass in the active limbs. Although significant sex differences of O2 transfer and power output are shown, the sex-specific aerobic performance was roughly proportional to active muscle volume (both when comparing individuals on a given type of ergometer and when comparing average scores of the several types of ergometer). However, the relationship was closer for steady power output than for peak O2 intake (where the scores for arm work were boosted by the use of accessory muscles and by hyperventilation). When breathing 12% O2, the 2-leg performance was substantially reduced (an average of 28.7% for O2 transport and 19.2% for power output). This effect dropped to 9.1% for O2 transport and 12% for power output in one-leg ergometry and was negligible for arm or arm plus shoulder work. It is argued that because of difficulty in perfusing small muscles, arm work is limited largely by the intrinsic power of the active muscles, that single-leg ergometry is limited rather equally by central circulatory and muscular factors, and that two-leg ergometry is almost entirely dependent on the central circulatory transport of O2.
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Smith, C. A., D. M. Ainsworth, K. S. Henderson, and J. A. Dempsey. "Differential timing of respiratory muscles in response to chemical stimuli in awake dogs." Journal of Applied Physiology 66, no. 1 (January 1, 1989): 392–99. http://dx.doi.org/10.1152/jappl.1989.66.1.392.
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We assessed changes in respiratory muscle timing in response to hyperpnea and shortened inspiratory and expiratory times caused by chemoreceptor stimuli in six awake dogs. Durations of postinspiratory inspiratory activity of costal and crural diaphragm (PIIA), the delay in diaphragm electromyogram (EMG) after the initiation of inspiratory airflow, postexpiratory expiratory activity of the transversus abdominis (PEEA), and the delay of abdominal expiratory muscle activity after the initiation of expiratory airflow were measured. In control, four out of six dogs showed PIIA [8–10% of expiratory time (TE)]; all showed delay of diaphragm [19% of inspiratory time (TI)], delay of abdominal muscle activation (21% of TE), and PEEA (24% of TI). Hypercapnia decreased PIIA (4–9% of TE), maintained diaphragm delay at near control values (23% of TI), increased PEEA (36% of TI), eliminated delay of abdominal muscle activation (4% of TE), and decreased end-expiratory lung volume (EELV). Hypocapnic hypoxia increased PIIA (24–25% of TE), eliminated diaphragm delay (3% of TI), eliminated PEEA (3% of TI), reduced delay of abdominal muscle activation (14% of TE), and increased EELV. Most of these effects of hypoxic hypocapnia vs. hypercapnia on the within-breath EMG timing parameters corresponded to differences in the magnitude of expiratory muscle activation. These changes exerted significant influences on flow rates and EELV.
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Schaeffer, Michele R., Cassandra T. Mendonca, Marc C. Levangie, Ross E. Andersen, Tanja Taivassalo, and Dennis Jensen. "Physiological mechanisms of sex differences in exertional dyspnoea: role of neural respiratory motor drive." Experimental Physiology 99, no. 2 (December 6, 2013): 427–41. http://dx.doi.org/10.1113/expphysiol.2013.074880.
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Kinkead, Richard, and Evelyn Schlenker. "Sex-based differences in respiratory control: Progress in basic physiology and clinical research." Respiratory Physiology & Neurobiology 245 (November 2017): 1–3. http://dx.doi.org/10.1016/j.resp.2017.08.013.
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Park, Song-Young, Jayson R. Gifford, Robert H. I. Andtbacka, Joel D. Trinity, John R. Hyngstrom, Ryan S. Garten, Nikolaos A. Diakos, et al. "Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?" American Journal of Physiology-Heart and Circulatory Physiology 307, no. 3 (August 1, 2014): H346—H352. http://dx.doi.org/10.1152/ajpheart.00227.2014.
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Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s−1·mg−1, P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g−1·min−1, P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s−1·mg−1, P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.
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Foltz, Steven, Fang Wu, Nasab Ghazal, Jennifer Q. Kwong, H. Criss Hartzell, and Hyojung J. Choo. "Sex differences in the involvement of skeletal and cardiac muscles in myopathic Ano5−/− mice." American Journal of Physiology-Cell Physiology 322, no. 2 (February 1, 2022): C283—C295. http://dx.doi.org/10.1152/ajpcell.00350.2021.
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Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by recessive mutations in the Anoctamin-5 gene ( ANO5, TMEM16E). Although ANO5 myopathy is not X-chromosome linked, we performed a meta-analysis of the research literature and found that three-quarters of patients with LGMD-R12 are males. Females are less likely to present with moderate to severe skeletal muscle and/or cardiac pathology. Because these sex differences could be explained in several ways, we compared males and females in a mouse model of LGMD-R12. This model recapitulates the sex differences in human LGMD-R12. Only male Ano5−/− mice had elevated serum creatine kinase after exercise and exhibited defective membrane repair after laser injury. In contrast, by these measures, female Ano5−/− mice were indistinguishable from wild type. Despite these differences, both male and female Ano5−/− mice exhibited exercise intolerance. Although exercise intolerance of male mice can be explained by skeletal muscle dysfunction, echocardiography revealed that Ano5−/− female mice had features of cardiomyopathy that may be responsible for their exercise intolerance. These findings heighten concerns that mutations of ANO5 in humans may be linked to cardiac disease.
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Lionikas, A., D. A. Blizard, D. J. Vandenbergh, M. G. Glover, J. T. Stout, G. P. Vogler, G. E. McClearn, and L. Larsson. "Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage." Physiological Genomics 16, no. 1 (December 16, 2003): 141–52. http://dx.doi.org/10.1152/physiolgenomics.00103.2003.
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The aim of the study was to explore the genetic architecture influencing weight of fast- and slow-twitch skeletal muscles. The weights of the slow-twitch soleus, the mixed gastrocnemius, the fast-twitch tibialis anterior (TA), and extensor digitorum longus (EDL) muscles were 11–34% greater ( P < 0.001) in 200-day-old C57BL/6J (B6) than in DBA/2J (D2) mice. Male muscles were 13–28% larger than female ( P < 1 × 10−5, no strain by sex interaction). The sex-related difference in muscle weight, however, varied significantly among the 23 derivative BXD recombinant inbred (RI) strains (strain by sex interaction for soleus, P < 0.01; TA, P < 1 × 10−4; EDL, not significant; and gastrocnemius, P < 0.001). Quantitative trait loci (QTL) affecting muscle weight were mapped in an F2 intercross of B6 and D2 mice (B6D2F2) and BXD RIs. A total of 10 autosomal, muscle-specific, but not muscle-type-specific, QTL, explaining a total of 5.4, 7.7, 22.9, and 8.6% of phenotypic variance for soleus, TA, EDL, and gastrocnemius muscles, respectively, were found across chromosomes 1 (Chr 1), 2, 3 (female-specific), 5 (two), 6, 7, 8, and 9 in B6D2F2 mice. The QTL on Chr 8 for EDL and the female-specific QTL on Chr 3 for gastrocnemius muscles were statistically significant, but the remaining QTL were at the suggestive level of statistical significance. Ten QTL on Chr 1, 2, 4, 5, 7, 8, 14, 17 (two), and 19 were identified in BXD RIs. Half of the QTL in BXD RIs had pleiotropic effects and were at the suggestive level of significance (except for the significant QTL for gastrocnemius muscle on Chr 17). The B6D2F2 nominated QTL on Chr 8 for EDL weight was validated in BXD RIs ( P < 0.03). Support intervals for the QTL on Chr 1 and 5 overlapped between B6D2F2 and BXD RIs. An epistatic interaction between markers on Chr 1 and 17 affected gastrocnemius weight in BXD RIs. The interaction was not, however, validated in the B6D2F2 population. Our results indicate that the differences in muscle weight in the B6 and D2 segregating populations were the outcome of a polygenic system, with each factor contributing a small amount to the phenotypic variance and the genetic architecture affecting muscle weight was muscle specific, but not muscle-type specific, and in some instances sex specific.
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Strittmatter, Rachel R., and James C. Schadt. "Sex differences in the respiratory response to hemorrhage in the conscious, New Zealand white rabbit." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 5 (May 2007): R1963—R1969. http://dx.doi.org/10.1152/ajpregu.00494.2006.
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In conscious animals, the response to hemorrhage is biphasic. During phase 1, arterial pressure is maintained. Phase 2 is characterized by profound hypotension. Despite allied roles, less is known about the integrated cardiovascular and respiratory response to blood loss in conscious animals. We evaluated cardiorespiratory changes during hemorrhage to test the hypotheses that 1) respiratory rate (RR) and blood gases do not change during phase 1; 2) RR increases during phase 2; and 3) RR and blood gas changes during hemorrhage are similar in males and females. We measured mean arterial pressure, RR, and blood gases during hemorrhage in 16 conscious, chronically prepared, male and female New Zealand white rabbits. We removed venous blood until mean arterial pressure was ≤40 mmHg. Sex did not affect mean arterial pressure, heart rate, PaO2, PaCO2, or pH during hemorrhage or the blood loss required to induce phase 2. PaCO2 decreased significantly from 37 ± 1 to 33 ± 1 and 29 ± 1 mmHg ( P < 0.001) during phase 1 and 2, respectively. Before hemorrhage, PaO2 was 87 ± 2 mmHg. PaO2 was unchanged in phase 1 (92 ± 2 mmHg) but increased in phase 2 (101 ± 2 mmHg; P < 0.001). Body temperature, PvCO2 (thoracic vena cava), and ventilation-perfusion mismatch (A-a gradient) were unchanged during phases 1 and 2. Neither sex increased RR during phase 1. While males doubled RR during phase 2, RR in females did not change ( P < 0.001). Thus, while PaCO2 decreases in phase 1 and phase 2, the decreases are achieved in different ways across the two phases and in the two sexes.
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Lingappan, Krithika, Weiwu Jiang, Lihua Wang, and Bhagavatula Moorthy. "Sex-specific differences in neonatal hyperoxic lung injury." American Journal of Physiology-Lung Cellular and Molecular Physiology 311, no. 2 (August 1, 2016): L481—L493. http://dx.doi.org/10.1152/ajplung.00047.2016.
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Male sex is considered an independent predictor for the development of bronchopulmonary dysplasia (BPD) after adjusting for other confounders. BPD is characterized by an arrest in lung development with marked impairment of alveolar septation and vascular development. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. In this investigation, we tested the hypothesis that male neonatal mice will be more susceptible to hyperoxic lung injury and will display larger arrest in lung alveolarization. Neonatal male and female mice (C57BL/6) were exposed to hyperoxia [95% FiO2, postnatal day (PND) 1–5] and euthanized on PND 7 and 21. Extent of alveolarization, pulmonary vascularization, inflammation, and modulation of the NF-κB pathway were determined and compared with room air controls. Macrophage and neutrophil infiltration was significantly increased in hyperoxia-exposed animals but was increased to a larger extent in males compared with females. Lung morphometry showed a higher mean linear intercept (MLI) and a lower radial alveolar count (RAC) and therefore greater arrest in lung development in male mice. This was accompanied by a significant decrease in the expression of markers of angiogenesis (PECAM1 and VEGFR2) in males after hyperoxia exposure compared with females. Interestingly, female mice showed increased activation of the NF-κB pathway in the lungs compared with males. These results support the hypothesis that sex plays a crucial role in hyperoxia-mediated lung injury in this model. Elucidation of the sex-specific molecular mechanisms may aid in the development of novel individualized therapies to prevent/treat BPD.
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Holmbäck, Anna Maria, Michelle M. Porter, David Downham, Jesper L. Andersen, and Jan Lexell. "Structure and function of the ankle dorsiflexor muscles in young and moderately active men and women." Journal of Applied Physiology 95, no. 6 (December 2003): 2416–24. http://dx.doi.org/10.1152/japplphysiol.00517.2002.
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The aim was to investigate determinants of ankle dorsiflexor muscle (DF) strength and size in moderately active young men and women ( n = 30; age 20–31 yr). Concentric (Con) and eccentric (Ecc) strength were measured isokinetically. Magnetic resonance imaging was used to determine the muscle cross-sectional area (CSA). Multiple biopsies were obtained from the tibialis anterior muscle to determine total numbers, areas (Area I and II) and proportions (Prop I and II) of type I and II fibers, respectively, and relative contents of myosin heavy chain (MHC) isoforms MHC1, MHC2a, and MHC2x. Women had lower Con and Ecc strength (24 and 27%; P < 0.01), smaller CSA (19%; P < 0.001), lower Ecc DF specific strength (strength/CSA) (10%; P < 0.01), and smaller Area I and Area II (21 and 31%; P < 0.01) than men. Prop I, MHC1, estimated total number of fibers, and Con DF specific strength were similar for both sexes. Con DF strength was up to 72% determined by CSA and Prop I, and Ecc DF strength was up to 81% determined by CSA, Prop I, and sex; variables other than CSA explained at most 9%. Body weight and fiber areas explained >50% of the variation in CSA. In conclusion, CSA was the predominant determinant of DF strength, CSA was to a great extent determined by the body weight and the sizes of muscle fibers, and sex differences in Ecc specific strength require further study.
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Maarsingh, E. J. W., L. A. van Eykern, A. B. Sprikkelman, M. O. Hoekstra, and W. M. C. van Aalderen. "Respiratory muscle activity measured with a noninvasive EMG technique: technical aspects and reproducibility." Journal of Applied Physiology 88, no. 6 (June 1, 2000): 1955–61. http://dx.doi.org/10.1152/jappl.2000.88.6.1955.
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A new method is being developed to investigate airway obstruction in young children by means of noninvasive electromyography (EMG) of diaphragmatic and intercostal muscles. The purpose of this study was to evaluate the reproducibility of the EMG measurements. Eleven adults, 39 school children (20 healthy, 19 asthmatic), and 16 preschool children were studied during tidal breathing on separate occasions: two for adults with a time interval of 3 wk and three for children with time intervals of 1 and 24 h. Single electrodes were placed on the second intercostal space left and right of the sternum and at the height of the frontal and the dorsal diaphragm. Bipolar electrode pairs were placed on the rectus abdominis muscle. A newly designed digital physiological amplifier without any analog filtering was used to measure the EMG signals. Except for the average dorsal diaphragm EMG derivation in healthy school children on the second occasion, a significant correlation between the mean peak-to-peak inspiratory activity of average diaphragmatic and intercostal EMG was found in the different age groups on the different measurement occasions ( P< 0.05). To assess the repeatability, we described the agreement between the repeated measurements within the same subjects. No significant differences were found between the measurements on the separate occasions. Our observations indicate that the EMG signals derived from the diaphragm and intercostal muscles are, in different age groups with and without asthma, reproducible during tidal breathing.
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Stock, Matt S., Dustin J. Oranchuk, Adam M. Burton, and David C. Phan. "Age-, sex-, and region-specific differences in skeletal muscle size and quality." Applied Physiology, Nutrition, and Metabolism 45, no. 11 (November 2020): 1253–60. http://dx.doi.org/10.1139/apnm-2020-0114.
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Ultrasonography-derived cross-sectional area (CSA) and echo intensity (EI) are increasingly utilized by investigators to study muscle size and quality, respectively. We sought to examine age, sex, and region (proximal, middle, distal) differences in vastus lateralis and rectus femoris CSA and EI, and determine whether correction for subcutaneous fat thickness influences the magnitude of EI differences. Fifteen younger men (mean age = 23 years), 15 younger women (aged 21 years), 11 older men (aged 74 years), and 15 older women (aged 70 years) participated. Clear differences were observed among age, sex, and region for vastus lateralis CSA (p ≤ 0.013, d = 0.38–0.73), whereas rectus femoris CSA was only different between younger and older participants at the proximal region (p = 0.017, d = 0.65). Uncorrected EI was greatest at the distal region of both muscles (p < 0.001, d = 0.59–1.38), with only the younger men having significantly lower EI values than the other groups (p ≤ 0.043, d = 0.37–0.63). Subcutaneous fat correction resulted in a marked increase in the magnitude of sex-specific EI differences (p ≤ 0.032, d ≥ 0.42). Additionally, subcutaneous fat correction increased the uniformity of EI throughout the thigh. These findings highlight considerable region-specific differences in muscle size and quality among younger and older men and women and highlight the need to correct for subcutaneous fat thickness when examining EI. Novelty Rectus femoris CSA is similar between younger and older adults except at the most proximal site evaluated. Age- and sex-specific differences in uncorrected EI are nonuniform across the thigh. Correction for subcutaneous fat thickness substantially increased EI in women, resulting in greater sex differences.
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Dempsey, Jerome A., and Peter D. Wagner. "Exercise-induced arterial hypoxemia." Journal of Applied Physiology 87, no. 6 (December 1, 1999): 1997–2006. http://dx.doi.org/10.1152/jappl.1999.87.6.1997.
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Exercise-induced arterial hypoxemia (EIAH) at or near sea level is now recognized to occur in a significant number of fit, healthy subjects of both genders and of varying ages. Our review aims to define EIAH and to critically analyze what we currently understand, and do not understand, about its underlying mechanisms and its consequences to exercise performance. Based on the effects on maximal O2uptake of preventing EIAH, we suggest that mild EIAH be defined as an arterial O2 saturation of 93–95% (or 3–4% <rest), moderate EIAH as 88–93%, and severe EIAH as <88%. Both an excessive alveolar-to-arterial[Formula: see text] difference (a-a Do 2) (>25–30 Torr) and inadequate compensatory hyperventilation (arterial [Formula: see text] >35 Torr) commonly contribute to EIAH, as do acid- and temperature-induced shifts in O2 dissociation at any given arterial [Formula: see text]. In turn, expiratory flow limitation presents a significant mechanical constraint to exercise hyperpnea, whereas ventilation-perfusion ratio maldistribution and diffusion limitation contribute about equally to the excessivea-a Do 2. Exactly how diffusion limitation is incurred or how ventilation-perfusion ratio becomes maldistributed with heavy exercise remains unknown and controversial. Hypotheses linked to extravascular lung water accumulation or inflammatory changes in the “silent” zone of the lung's peripheral airways are in the early stages of exploration. Indirect evidence suggests that an inadequate hyperventilatory response is attributable to feedback inhibition triggered by mechanical constraints and/or reduced sensitivity to existing stimuli; but these mechanisms cannot be verified without a sensitive measure of central neural respiratory motor output. Finally, EIAH has detrimental effects on maximal O2 uptake, but we have not yet determined the cause or even precisely identified which organ system, involved directly or indirectly with O2 transport to muscle, is responsible for this limitation.
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Tomita, Hidehito, Yoshiki Fukaya, Tomomi Ueda, Shota Honma, Eriya Yamashita, Yoshiji Yamamoto, Etsuko Mori, and Katsuyoshi Shionoya. "Deficits in task-specific modulation of anticipatory postural adjustments in individuals with spastic diplegic cerebral palsy." Journal of Neurophysiology 105, no. 5 (May 2011): 2157–68. http://dx.doi.org/10.1152/jn.00569.2010.
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We examined whether individuals with spastic diplegic cerebral palsy (SDCP) have the ability to utilize lower leg muscles in anticipatory postural adjustments (APAs) associated with voluntary arm movement while standing, as well as the ability to modulate APAs with changes in the degree of postural perturbation caused by arm movement. Seven individuals with spastic diplegia (SDCP group, 12–22 yr of age) and seven age- and sex-matched individuals without disability (control group) participated in this study. Participants flexed both shoulders and lifted a load under two different load conditions, during which electromyographic activities of focal and postural muscles were recorded. Although the timing of anticipatory activation of the erector spinae and medial hamstring (MH) muscles was similar in the two participant groups, that of the gastrocnemius (GcM) muscle was significantly later in the SDCP group than in the control group. An increase in anticipatory postural muscle activity with an increase in load was observed in MH and GcM in the control group but not in GcM in the SDCP group. The degree of modulation in MH was significantly smaller in the SDCP group than in the control group. An additional experiment confirmed that these differences in APAs between the two participant groups were unlikely to be attributable to their differences in initial standing posture before load lift. The present findings suggest that lower leg muscles play a minor role in APAs in individuals with spastic diplegia. In addition, it is likely that these individuals have difficulty modulating anticipatory postural muscle activity with changes in the degree of postural perturbation.
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Franco, Patricia, Benjamin Putois, Aurore Guyon, Aude Raoux, Maria Papadopoulou, Anne Guignard-Perret, Flora Bat-Pitault, Sarah Hartley, and Sabine Plancoulaine. "Sleep during development: Sex and gender differences." Sleep Medicine Reviews 51 (June 2020): 101276. http://dx.doi.org/10.1016/j.smrv.2020.101276.
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Meza, Sonia, Manuel Mendez, Michele Ostrowski, and Magdy Younes. "Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects." Journal of Applied Physiology 85, no. 5 (November 1, 1998): 1929–40. http://dx.doi.org/10.1152/jappl.1998.85.5.1929.
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Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (Vt) and elastance (Vt sp ⋅ E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the[Formula: see text] (difference between eupneic[Formula: see text] and CO2 apneic threshold) and by ΔRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2–5 min each) until PB developed or the subject awakened. End-tidal [Formula: see text], Vt, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(ΔPaw + Pmus)/Pmus], where ΔPaw is peak Paw − continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. [Formula: see text]ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to −3.5 min−1). With use of stepwise regression, PSV(PB) was significantly correlated with Vt sp( P = 0.001), E ( P = 0.00009),[Formula: see text]( P = 0.007), and ΔRR ( P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 Vt sp + 0.3E − 0.4 [Formula: see text] − 0.34 ΔRR − 3.4 ( r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5–3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a[Formula: see text] apneic threshold exists during sleep at 1.5–5.8 Torr below eupneic[Formula: see text], 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.
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Ueno, Ryo, Takashi Nagai, Nathaniel A. Bates, Timothy E. Hewett, and Nathan D. Schilaty. "Sex differences in passive and active stiffness of the knee flexor muscles during dynamic perturbation test: principal component analysis." Somatosensory & Motor Research 37, no. 4 (September 23, 2020): 293–99. http://dx.doi.org/10.1080/08990220.2020.1824905.
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Kocha, K. M., C. E. Genge, and C. D. Moyes. "Origins of interspecies variation in mammalian muscle metabolic enzymes." Physiological Genomics 43, no. 14 (July 2011): 873–83. http://dx.doi.org/10.1152/physiolgenomics.00025.2011.
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Do the transcriptional mechanisms that control an individual's mitochondrial content, PGC1α (peroxisome proliferator-activated receptor γ coactivator-1α) and NRF1 (nuclear respiratory factor-1), also cause differences between species? We explored the determinants of cytochrome c oxidase (COX) activities in muscles from 12 rodents differing 1,000-fold in mass. Hindlimb muscles differed in scaling patterns from isometric (soleus, gastrocnemius) to allometric (tibialis anterior, scaling coefficient = −0.16). Consideration of myonuclear domain reduced the differences within species, but interspecies differences remained. For tibialis anterior, there was no significant scaling relationship in mRNA/g for COX4-1, PGC1α, or NRF1, yet COX4-1 mRNA/g was a good predictor of COX activity (r2 = 0.55), PGC1α and NRF1 mRNA correlated with each other (r2 = 0.42), and both could predict COX4-1 mRNA (r2 = 0.48 and 0.52) and COX activity (r2 = 0.55 and 0.49). This paradox was resolved by multivariate analysis, which explained 90% of interspecies variation, about equally partitioned between mass effects and PGC1α (or NRF1) mRNA levels, independent of mass. To explore the determinants of PGC1α mRNA, we analyzed 52 mammalian PGC1α proximal promoters and found no size dependence in regulatory element distribution. Likewise, the activity of PGC1α promoter reporter genes from 30 mammals showed no significant relationship with body mass. Collectively, these studies suggest that not all muscles scale equivalently, but for those that show allometric scaling, transcriptional regulation of the master regulators, PGC1α and NRF1, does not account for scaling patterns, though it does contribute to interspecies differences in COX activities independent of mass.
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Peng, Heng, Takuji Kawamura, Hiroshi Akiyama, Lili Chang, Risa Iwata, and Isao Muraoka. "Effects of sex differences on breath-hold diving performance." Respiratory Physiology & Neurobiology 293 (November 2021): 103721. http://dx.doi.org/10.1016/j.resp.2021.103721.
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