Auswahl der wissenschaftlichen Literatur zum Thema „Respiratory muscles Physiology Sex differences“

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.

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.

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.

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.

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.

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.

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.

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

"May 2002." Bibliography: leaves 123-144. Aspects of the control of ventilation and an upper airway dilator muscle (genioglossus) are compared between healthy men and women, in an attempt to identify a gender difference that may contribute to the high male prevalence of sleep apnea.

Dyspnea, the awareness of an increase in breathing discomfort, is commonly experienced during physical activity in healthy individuals and in patients with cardiopulmonary disease. It is well established that the intensity of perceived dyspnea is consistently higher during exercise in healthy women compared to men, regardless of age, height, and weight. However, the mechanism(s) of this sex-related difference in activity-related dyspnea is/are poorly understood and represented the primary focus of this thesis.Compared to men, women have smaller lungs, narrower airways, and weaker breathing muscles. These anatomical differences manifest as greater mechanical constraints on ventilation, particularly during the stress of exercise when ventilatory requirements are high. In addition, the amount of work the breathing muscles must perform in order to move a given volume of air into and out of the lungs during exercise is considerably higher in women than men. It is reasonable to predict that, because of these differences, the central nervous system must activate the respiratory muscles (particularly the diaphragm) to a greater extent during exercise in women compared to men to achieve the same level of ventilation and that this higher respiratory muscle activation may account for the increased perception of activity-related dyspnea in women. While it is not feasible to directly measure the neural output of the brains' respiratory control center at rest or during exercise in humans, central neural respiratory motor drive can be assessed indirectly by quantifying the electromyogram of the crural diaphragm (EMGdi) using a special electrode catheter positioned in an individual's esophagus. To date, no previous study, in health or disease, has examined whether the combination of relatively greater dynamic mechanical ventilatory constraints and a higher EMGdi (i.e., neuromechanical uncoupling of the respiratory system) during exercise in women is responsible, at least in part, for sex differences in activity-related dyspnea. To address this important question we compared detailed assessments of EMGdi, respiratory muscle function, ventilation, breathing pattern, operating lung volumes, cardio-metabolic function, and dyspnea intensity and unpleasantness ratings during symptom-limited incremental bicycle exercise testing in 25 healthy, young (20-40 yrs) women and 25 age-matched men. Our results demonstrated relatively greater mechanical constraints on tidal volume expansion at any given ventilation during exercise in women compared to men. The present study was the first to demonstrate that esophageal electrode catheter-derived measures of EMGdi were consistently higher at any given ventilation during exercise in women compared with men and that these differences reflected, in large part, the presence of relatively greater dynamic mechanical ventilatory constraints in women. In keeping with the results of previous studies, sensory intensity and unpleasantness ratings of dyspnea were higher at any given ventilation during submaximal exercise in women compared to men. However, in contrast to our a priori hypothesis, these perceptual differences could not be readily explained by greater neuromechanical uncoupling of the respiratory system, but primarily reflected the awareness of a relatively higher EMGdi (or central neural respiratory motor drive) needed to achieve any given ventilation during exercise in the setting of greater dynamic mechanical ventilatory constraints in women. These findings may have implications for our understanding of the physiological mechanisms of sex differences in activity-related dyspnea in variants of health (e.g., aging) and in patients with cardiopulmonary disease.
La dyspnée, définie comme la conscience d'une augmentation de gêne respiratoire, est souvent connu pendant l'activité physique chez les sujets sains ainsi que chez les patients ayant une maladie cardio-pulmonaire. Il est bien établi que l'intensité de la dyspnée perçue est systématiquement plus élevée au cours de l'exercice chez les femmes en bonne santé par rapport aux hommes, indépendamment de l'âge, de la taille et du poids. Cependant le/les mécanisme(s) de cette différence sont mal compris et la clarification de ceux-ci comportent l'objet principal de la thèse en question.Comparativement aux hommes, les femmes ont de plus petits poumons, des voies respiratoires plus étroites et des muscles respiratoires plus faibles. Ces différences anatomiques se manifestent par de plus grandes contraintes mécaniques sur la ventilation, en particulier pendant le stress de l'exercice lorsque les besoins ventilatoires sont élevés. Par conséquent, le travail que les muscles respiratoires doivent effectuer afin de déplacer un volume défini d'air dans les poumons pendant l'exercice est considérablement plus élevé chez les femmes que chez les hommes. En raison de ces différences, nous prévoyons que le système nerveux central doit activer les muscles respiratoires (notamment le diaphragme) dans une plus grande mesure chez les femmes pour atteindre le même niveau de ventilation et que cette activation supérieure peut expliquer la perception accrue de la dyspnée liée à l'activité chez les femmes. Même s'il n'est pas possible de mesurer directement les signaux envoyés par le centre de contrôle respiratoire chez l'homme, le contrôle moteur de la respiration peut être évalué indirectement en quantifiant l'électromyogramme du diaphragme crural (EMGdi) en utilisant un cathéter à électrode spécialisée placée dans l'oesophage d'un individu. À ce jour, aucune étude n'a examiné si la combinaison de contraintes ventilatoires mécaniques plus grandes et d'un EMGdi plus élevé pendant l'exercice chez les femmes est responsable des différences de sexe dans la dyspnée liée à l'activité. Nous avons donc comparé des évaluations détaillées de EMGdi, de fonction musculaire respiratoire, de ventilation, de modèle de respiration, de volumes pulmonaires opérationnels, de fonction cardio-métabolique, et d'intensité de la dyspnée et des cotes de désagréments lors de tests d'exercice incrémental de vélo dans 25 jeunes (20-40 yrs) femmes saines et 25 hommes sains du même âge. Nos résultats démontrent des contraintes mécaniques sur l'expansion du volume courant pendant l'exercice plus fortes chez les femmes par rapport aux hommes. La présente étude est la première à démontrer que les mesures de cathéter à électrodes œsophagiennes dérivés de EMGdi étaient systématiquement plus élevés peu importe le niveau de ventilation au cours de l'exercice chez les femmes par rapport aux hommes et que ces différences reflètent, en grande partie, la présence de contraintes ventilatoires mécaniques dynamiques relativement plus grande chez les femmes. En accord avec les résultats d'études antérieures, l'intensité sensorielle et le désagrément de dyspnée ont été supérieurs à n'importe quelle ventilation donnée au cours de l'exercice sous-maximal chez les femmes par rapport aux hommes. Cependant, contrairement à notre hypothèse a priori, ces différences de perception ne peuvent être facilement expliquées par un plus grand découplage neuromécanique du système respiratoire et reflètent la conscience d'une EMGdi relativement élevée (ou moteur d'entraînement respiratoire neural central) nécessaire pour atteindre une ventilation donnée pendant l'exercice dans le cadre de contraintes ventilatoires mécaniques dynamiques plus grande chez les femmes. Ces résultats pourraient avoir des implications dans notre compréhension des mécanismes de différences de sexe dans la dyspnée liée à l'activité dans les variantes de la santé et chez les patients ayant une maladie cardio-pulmonaire.

The aim of this investigation was to compare the acute anabolic and catabolic responses of male and female vastus lateralis (VL) and soleus (SOL) muscles in response to resistance exercise (RE). Muscle biopsies from the VL of 7 males (26±3 y, 75±8 kg) and 7 females (25±3 y, 59±5 kg) were obtained before, and 2 and 6 h after 4 x 7 supine-squat, and 4 x 14 calf-press exercises at maximal effort using inertial ergometry. The mRNA levels of select myogenic (MyoD, myogenin, MRF4), proteolytic (atrogin-1 , MuRF-1), myostatin, and inflammatory (IL-6, -8, -15) genes were quantified using real-time RT-PCR. Male VL vs SOL: The SOL had higher basal mRNA levels of myogenic, proteolytic, and inflammatory genes. After exercise, the myogenic response was similar between the VL and SOL. Both muscles increased MuRF-1 similarly at 2 h, whereas 6 h post-RE proteolytic gene expression (GE) was suppressed in the VL but not in the SOL. The SOL had a reduction in myostatin GE, and a more robust inflammatory response compared to the VL. These findings indicate a more favorable growth response in the VL. Gender comparisons: VL – Basally, the male VL had higher levels of myogenic, proteolytic, myostatin, and inflammatory mRNA compared to the female VL. After exercise, both genders increased myogenic GE similarly. Both genders increased MuRF-1 initially, with females also increasing atrogin-1 and myostatin post-RE. At 6 h, males decreased proteolytic GE to below basal levels. Females also had a greater inflammatory response than males. These findings indicate a greater growth response to RE in the male VL as compared to the female VL. SOL – After exercise, both genders increased myogenic GE in the SOL, but only males increased MyoD expression. Males increased MuRF-1 mRNA but decreased myostatin GE, while females decreased atrogin-1. The inflammatory response was similar between males and females. Despite the modest differences, the net response of the female and male SOL was similar, and indicated a molecular response slightly favorable for growth.
School of Physical Education, Sport, and Exercise Science

"May 2002."
Bibliography: leaves 123-144.
xiv, 144 leaves : ill. ; 30 cm.
Aspects of the control of ventilation and an upper airway dilator muscle (genioglossus) are compared between healthy men and women, in an attempt to identify a gender difference that may contribute to the high male prevalence of sleep apnea.
Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2002