Diaphragmatic Fatigue Research Articles

Features of inspiratory muscles’ functional state in chronic heart failure with preserved ejection fraction

BACKGROUND: It is known that chronic heart failure contributes to the development of multiple organ pathology, including skeletal muscle pathology. AIM: To determine the strength and electrical activity of the inspiratory muscles in patients with chronic heart failure with preserved left ventricular ejection fraction. MATERIAL AND METHODS: The study involved 80 patients of both sexes aged 45 to 74 years, who were divided into three groups: the first group consisted of 24 patients with stage IIA chronic heart failure, the second group consisted of 20 patients with stage I chronic heart failure, and the third group (control group) consisted of 36 patients without chronic heart failure. All patients underwent serum N-terminal fragment of natriuretic brain propeptide determination, 6-minute walk test, measurement of inspiratory muscle strength, and surface electromyography of the inspiratory muscles using three exercise tests. The statistical significance of differences between the groups was assessed using the Mann–Whitney test and Pearson χ2. RESULTS: It was found that when dividing the groups by gender, the maximum inspiratory pressure in women of the first group was lower than in women of the control group by 31.5% (p=0.006). In patients of the first group, a smaller increase in the amplitude of the diaphragm electromyogram was recorded in the 1st test — with maintaining an inspiratory effort of 30% power for 15 s by 27.9% (p=0.010), 26.1% (p=0.025) and 40.7% (p=0.033) at the 5th, 10th and 15th seconds, respectively, in the 2nd test — with maintaining an inspiratory effort of 50% power for 5 s, by 32.6% (p=0.041) at the 5th second, in the 3rd test — with maintaining an inspiratory effort of 70% power for 5 s, by 42.8% (p=0.009) at the 5th second compared to the control group. At the same time, a more pronounced decrease in the electromyogram frequency was noted in the 1st sample — by 24.2% (p=0.048), 24.7% (p=0.030) compared to the control group, which serves as a sign of fatigue. On the accessory inspiratory muscles, the amplitude increase was higher in patients of the first group compared to the control group, which indicates activation of additional motor units: on the external intercostal muscles in the 1st sample — by 31.7% (p=0.032), 37.9% (p=0.044), in the 2nd sample — by 28.9% (p=0.048), 43.1% (p=0.036); on the sternocleidomastoid muscle in the 1st sample — by 66.1% (p=0.033), 49.4% (p=0.043), in the 2nd sample — by 128.6% (p=0.032). CONCLUSION: In patients with chronic heart failure stage IIA, surface electromyography using stress tests revealed diaphragm fatigue and increased activity of accessory inspiratory muscles.

Influence of an inspiratory muscle fatigue protocol on older adults on respiratory muscle strength and heart rate variability. A randomized controlled trial.

Inspiratory muscle fatigue has been shown to have effects on the autonomic nervous system and physical condition. This study aimed to evaluate the influence of an inspiratory muscle fatigue protocol on respiratory muscle strength and heart rate variability in older adults. A randomized controlled clinical trial with double-blinding was carried out involving 24 individuals over 60 years old who demonstrated physical independence in walking and movement. Participants were distributed randomly into three groups: Inspiratory muscle fatigue, activation and control. Measurements of heart rate variability, diaphragmatic ultrasound, and maximum inspiratory pressure were taken at two stages: prior to the intervention (T1) and directly after treatment (T2). The inspiratory muscle fatigue group exhibited decrease scores in respiratory and heart rate variability subsequent to undergoing the diaphragmatic fatigue intervention compared to both the activation and control groups (p < 0.05). Conversely, the activation group demonstrated higher values in heart rate variability and respiratory capacity variables following the inspiratory muscle activation training (p < 0.05). Fatigue of the inspiratory musculature appears to negatively impact heart rate variability and inspiratory muscle strength in older adults. https://clinicaltrials.gov/study/NCT06269042, identifier: NCT06269042.

No effect of aerobic fitness on exercise-induced diaphragm fatigue in females.

We tested the hypothesis that the incidence and magnitude of diaphragm fatigue following high-intensity exercise would be lower in females with a high aerobic capacity (Hi-Fit) compared with healthy females with an average aerobic fitness (Avg-Fit). Participants were assigned to groups based on their peak O2 uptake (V̇o2peak) obtained during cycle exercise: Hi-Fit n = 9, V̇o2peak ≥ 56.1 ± 3.4 mL·kg-1·min-1 versus Avg-Fit n = 9, V̇o2peak ≤ 35.7 ± 4.9 mL·kg-1·min-1. On the second day, diaphragm fatigue was assessed before and after constant load exercise test to exhaustion. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess diaphragm fatigue by measurement of transdiaphragmatic twitch pressure (Pdi,tw). Both groups exercised at >90% of V̇o2peak for a similar duration (Hi-Fit: 546.1 ± 177.8 vs. Avg-Fit: 559.3 ± 175.0 s, P = 0.9). Diaphragm fatigue was defined as a ≥15% reduction in Pdi,tw, approximately two times greater than the coefficient of variation. The mean group average reduction in Pdi,tw following exercise in the Hi-Fit (17.5%) and Avg-Fit groups (12.2%) was not different between groups (P = 0.2). The Hi-Fit group performed exercise at a higher absolute work rate that elicited significantly greater ventilatory work and inspiratory muscle force output. The Hi-Fit group did not experience greater fatigue compared with the Avg-Fit group, which we attribute to a greater reliance on accessory respiratory muscle recruitment, to training-induced increases in the aerobic capacity of the diaphragm, or a combination of the two. In summary, aerobic fitness is not predictive of exercise-induced diaphragm fatigue in healthy females.NEW & NOTEWORTHY We hypothesized that females with a high aerobic capacity would be resistant to exercise-induced diaphragm fatigue relative to healthy but untrained females. We assessed the pressure generated by the diaphragm following exhaustive exercise by stimulating the phrenic nerves. The magnitude and incidence of fatigue were similar between groups. Despite having higher ventilatory demands during exercise highly trained females were resistant to greater diaphragm fatigue. Aerobic fitness is not predictive of exercise-induced diaphragm fatigue in females.

Uncovering Diaphragm Cramp in SIDS and Other Sudden Unexpected Deaths.

The diaphragm is the primary muscle of respiration. Here, we disclose a fascinating patient's perspective that led, by clinical reasoning alone, to a novel mechanism of spontaneous respiratory arrests termed diaphragm cramp-contracture (DCC). Although the 7-year-old boy survived its paroxysmal nocturnal "bearhug pain apnea" episodes, essentially by breathing out to breathe in, DCC could cause sudden unexpected deaths in children, especially infants. Diaphragm fatigue is central to the DCC hypothesis in SIDS. Most, if not all, SIDS risk factors contribute to it, such as male sex, young infancy, rebreathing, nicotine, overheating and viral infections. A workload surge by a roll to prone position or REM-sleep inactivation of airway dilator or respiratory accessory muscles can trigger pathological diaphragm excitation (e.g., spasms, flutter, cramp). Electromyography studies in preterm infants already show that diaphragm fatigue and sudden temporary failure by transient spasms induce apneas, hypopneas and forced expirations, all leading to hypoxemic episodes. By extension, prolonged spasm as a diaphragm cramp would induce sustained apnea with severe hypoxemia and cardiac arrest if not quickly aborted. This would cause a sudden, rapid, silent death consistent with SIDS. Moreover, a unique airway obstruction could develop where the hypercontracted diaphragm resists terminal inspiratory efforts by the accessory muscles. It would disappear postmortem. SIDS autopsy evidence consistent with DCC includes disrupted myofibers and contraction band necrosis as well as signs of agonal breathing from obstruction. Screening for diaphragm injury from hypoxemia, hyperthermia, viral myositis and excitation include serum CK-MM and skeletal troponin-I. Active excitation could be visualized on ultrasound or fluoroscopy and monitored by respiratory inductive plethysmography or electromyography.

Influence of an inspiratory muscle fatigue protocol on healthy youths on respiratory muscle strength, vertical jump performance and muscle oxygen saturation: a randomized controlled trial

BackgroundInspiratory muscle fatigue has been shown to have effects on limbs blood flow and physical performance. This study aimed to evaluate the influence of an inspiratory muscle fatigue protocol on respiratory muscle strength, vertical jump performance and muscle oxygen saturation in healthy youths.MethodsA randomized and double-blinded controlled clinical trial, was conducted. Twenty-four participants aged 18–45 years, non-smokers and engaged in sports activity at least three times a week for a minimum of one year were enrolled in this investigation. Participants were randomly assigned to three groups: Inspiratory Muscle Fatigue (IMFG), Activation, and Control. Measurements of vertical jump, diaphragmatic ultrasound, muscle oxygen saturation, and maximum inspiratory pressure were taken at two stages: before the intervention (T1) and immediately after treatment (T2).ResultsThe IMFG showed lower scores in muscle oxygen saturation and cardiorespiratory variables after undergoing the diaphragmatic fatigue intervention compared to the activation and control groups (p < 0.05). For the vertical jump variables, intragroup differences were found (p < 0.01), but no differences were shown between the three groups (p > 0.05).ConclusionsInspiratory muscle fatigue appears to negatively impact vertical jump performance, muscle oxygen saturation and inspiratory muscle strength in healthy youths.Trial registrationClinicalTrials.gov ID: NCT06271876. Date of registration 02/21/2024. https://clinicaltrials.gov/study/NCT06271876.

Differential effects of exercise intensity and tolerable duration on exercise-induced diaphragm and expiratory muscle fatigue.

We investigated the effect of exercise intensity and tolerable duration on the development of exercise-induced diaphragm and expiratory muscle fatigue. Ten healthy adults (25 ± 5 yr; 2 females) cycled to intolerance on three separate occasions: 1) 5% below critical power (<CP; heavy intensity); 2) ∼25% of the difference (Δ) between CP and peak ramp-incremental power (Δ25; severe intensity "longer"); and 3) ∼50% Δ (Δ50; severe intensity "shorter"). Diaphragm and expiratory muscle fatigue were quantified as a pre- to 5 min postexercise reduction in magnetically evoked transdiaphragmatic (Pditw) and gastric (Pgatw) twitch pressures, respectively. Exercise time was 34.5 ± 6.2 min, 10.2 ± 2.6 min, and 4.9 ± 0.7 min for <CP, Δ25, and Δ50 conditions, respectively. Oxygen uptake (V̇o2) at end-exercise was lower during <CP (87 ± 6% V̇o2peak) relative to Δ25 (97 ± 4% V̇o2peak) and Δ50 (99 ± 4% V̇o2peak) (P < 0.001). The pre- to postexercise decrease in Pditw was greater after Δ25 (-22 ± 12%) versus <CP (-13 ± 8%; P = 0.0499) and Δ50 (-14 ± 12%; P = 0.045). Conversely, the decrease in Pgatw from pre- to postexercise was not different between trials (<CP: -23 ± 15%; Δ25: -29 ± 15%; Δ50: -25 ± 16%) (P > 0.05). In conclusion, the magnitude of exercise-induced diaphragm fatigue was greater after longer-duration severe exercise than after shorter-duration severe and heavy exercise. By contrast, the magnitude of exercise-induced expiratory muscle fatigue was unaffected by exercise intensity and tolerable duration.NEW & NOTEWORTHY Exercise-induced respiratory muscle fatigue contributes to limiting exercise tolerance. Accordingly, better understanding the exercise conditions under which respiratory muscle fatigue occurs is warranted. Although heavy-intensity as well as short- and long-duration severe-intensity exercise performed to intolerance elicit diaphragm and expiratory muscle fatigue, we find, for the first time, that the relationship between exercise intensity, exercise duration, and the magnitude of exercise-induced fatigue is different for the diaphragm compared with the expiratory muscles.

Effects of aging on vasoconstrictor responses of diaphragm arterioles

Introduction: In health, the diaphragm is the most important inspiratory muscle and the only skeletal muscle that is continuously recruited throughout life. Because of the diaphragm’s importance to generating the exercise hyperpnea and wealth of evidence that diaphragm fatigue and exhaustion can impair exercise tolerance, we were interested in whether the exercise intolerance that attends older populations might be associated with altered diaphragm vasomotor control. While it is known that aging compromises peripheral skeletal muscle vasomotor control, it is not known if similar impairments are present in the respiratory muscle vasculature, namely the diaphragm. Therefore, we tested the hypothesis that advanced age decreases diaphragm arteriole contractile responses to alpha-adrenergic agonists. Methods: 4–5 month old Fischer rats and 22–24 month old Fischer rats were divided by age into two groups: young (Y) and old (O). In Y and O, diaphragm first order (1A) arterioles (~200μm diameter, ~2μm in length) were isolated, cannulated, and pressurized to develop spontaneous tone. Following this, contractile responses to cumulative doses of norepinephrine (NE) and phenylephrine (PE) (10−9 to 10−4M) were determined. Results and Conclusion: The physical characteristics of the two groups differed as O were heavier than Y. However, with respect to the diaphragm 1A arterioles, there were no differences in spontaneous tone development (%) or maximal diameter (μm) between Y (38 ± 4%; 132 ± 19μm) and O (37 ± 4%; 157 ± 14 μm; both P &gt;0.05). In diaphragm 1A arterioles, the maximal vasoconstrictor response to NE was also not different between O and Y animals (O: 37 ± 8% vs. Y: 45 ± 1%; p &gt; 0.05). However, the maximal vasoconstrictor response to PE was greater in Y compared to O (O: 29 ± 3% vs. Y: 39 ± 5%; p ≤ 0.05). These data support that aging may reduce a1 adrenergic receptor mediated vascular control, altering the vasoconstrictive responsiveness of diaphragm resistance vessels. We are increasing our group sizes to test the robustness of this conclusion. This work was supported by the Sustained Momentum for Investigators with Laboratories Established (SMILE) Grants awarded to T.I.M and D.C.P. by Kansas State University College of Veterinary Medicine and the National Institute on Aging 1R15AG078060 awarded to B.J.B and D.C.P. A.G.H and K.M.S. were financially supported by Ruth L. Kirschstein National Research Service Awards 1F31HL167618-01 and 1F31HL170643-01, respectively. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Diaphragmatic ultrasonography as a predictor of respiratory muscle fatigue in myasthenia gravis.

Easy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients. GMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N-TFdi and N-Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax. Thirty-four GMG patients and 30 healthy controls were enrolled. N-TFdi and N-Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15. DUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.

Diaphragmatic muscle function in term and preterm infants

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia—BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)—a measure of diaphragmatic strength, and the pressure–time index of the diaphragm (PTIdi)—a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi. Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function.What is Known:• The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively.• The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure–time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants.What is New:• Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue.• In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

Diaphragm Fatigue in SMNΔ7 Mice and Its Molecular Determinants: An Underestimated Issue.

Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons leading to muscle weakness and respiratory failure. Mitochondrial dysfunctions are found in the skeletal muscle of patients with SMA. For obvious ethical reasons, the diaphragm muscle is poorly studied, notwithstanding the very important role that respiratory involvement plays in SMA mortality. The main goal of this study was to investigate diaphragm functionality and the underlying molecular adaptations in SMNΔ7 mice, a mouse model that exhibits symptoms similar to that of patients with intermediate type II SMA. Functional, biochemical, and molecular analyses on isolated diaphragm were performed. The obtained results suggest the presence of an intrinsic energetic imbalance associated with mitochondrial dysfunction and a significant accumulation of reactive oxygen species (ROS). In turn, ROS accumulation can affect muscle fatigue, cause diaphragm wasting, and, in the long run, respiratory failure in SMNΔ7 mice. Exposure to the antioxidant molecule ergothioneine leads to the functional recovery of the diaphragm, confirming the presence of mitochondrial impairment and redox imbalance. These findings suggest the possibility of carrying out a dietary supplementation in SMNΔ7 mice to preserve their diaphragm function and increase their lifespan.

Enhanced endoplasmic reticulum RyR1 receptor phosphorylation leads to diaphragmatic dysfunction in septic rats

To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction. Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting. In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05). Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.

Paced breathing and respiratory movement responses evoked by bidirectional constant current stimulation in anesthetized rabbits.

Objective: Diaphragm pacing (DP) is a long-term and effective respiratory assist therapy for patients with central alveolar hypoventilation and high cervical spinal cord injury. The existing DP system has some limitations, especially high price, inconvenience preoperative evaluation methods and diaphragm fatigue easily. Our objective was to develop a DP system and evaluated reliability through hardware testing and animal experiments. Methods: A DP system with bidirectional constant current was designed, manufactured and tested. Effects of a wide range of stimulus amplitudes (range: .5-2.5mA) and frequencies (range: 10-250Hz) on airflow and corresponding inspired volume were investigated during DP. Differences in airflow characteristics under various stimulation parameters were evaluated using power function. ECG interference in diaphragm electromyography (EMGdi) was filtered out using stationary wavelet transform to obtain pure EMGdi (EMGdip). 80-min period with a tendency for diaphragm fatigue by root mean square (RMS) and centroid frequency (f c ) of EMGdip was studied. Results: The increase of stimulus frequency and amplitude in animals resulted in different degrees of increase in envoked volume. Significant difference in Airflow Index (b) between anesthesia and DP provided a simple, non-invasive and feasible solution for phrenic nerve conduction function test. Increased stimulation duration with the developed DP system caused less diaphragm fatigue. Conclusion: A modular, inexpensive and reliable DP was successfully developed. Its effectiveness was confirmed in animal experiments. Significance: This study is useful for design of future implantable diaphragmatic pacemakers for improving diaphragm fatigue and convenient assessment of respiratory activity in experiments.

Effects of hypoxia on exercise-induced diaphragm fatigue in healthy males and females.

Following high-intensity, normoxic exercise there is evidence to show that healthy females, on average, exhibit less fatigue of the diaphragm relative to males. In the present study, we combined hypoxia with exercise to test the hypothesis that males and females would develop a similar degree of diaphragm fatigue following cycle exercise at the same relative exercise intensity. Healthy young participants (n=10 male; n=10 female) with a high aerobic capacity (120% predicted) performed two time-to-exhaustion (TTE; ~85% maximum) cycle tests on separate days breathing either a normoxic or hypoxic (FiO2 =0.15) gas mixture. Fatigue of the diaphragm was assessed in response to cervical magnetic stimulation prior to, immediately post-exercise, 10-, 30-, and 60-min post-exercise. Males and females had similar TTE durations in normoxia (males: 690 ± 181 s; females: 852 ± 401 s) and hypoxia (males: 381 ± 160 s; females: 400 ± 176 s) (p > 0.05). Cycling time was significantly shorter in hypoxia versus normoxia in both males and females (p < 0.05) and did not differ on the basis of sex (p > 0.05). Following the hypoxic TTE tests, males and females experienced a similar degree of diaphragm fatigue compared to normoxia as shown by 20%-25% reductions in transdiaphragmatic twitch pressure. This occurred despite the fact that exercise time in hypoxia was substantially shorter relative to normoxia and the cumulative diaphragm work was lower. We also observed that females did not fully recover from diaphragm fatigue in hypoxia, whereas males did (p < 0.05). Sex differences in the rate of diaphragm contractility recovery following exercise in hypoxia might relate to sex-based differences in substrate utilization or diaphragm blood flow.

Co-activation of the diaphragm and external intercostal muscles through an adaptive closed-loop respiratory pacing controller.

Respiratory pacing is a promising alternative to traditional mechanical ventilation that has been shown to significantly increase the survival and quality of life after the neural control of the respiratory system has been compromised. However, current pacing approaches to achieve adequate ventilation tend to target only the diaphragm without pacing external intercostal muscles that are also activated during normal inspiration. Furthermore, the pacing paradigms do not allow for intermittent sighing, which carries an important physiological role. We hypothesized that simultaneous activation of the diaphragm and external intercostal muscles would improve the efficiency of respiratory pacing compared to diaphragm stimulation alone. We expanded an adaptive, closed-loop diaphragm pacing paradigm we had previously developed to include external intercostal muscle activation and sigh generation. We then investigated, using a rodent model for respiratory pacing, if simultaneous activation would delay the fatigability of the diaphragm during pacing and allow induction of appropriate sigh-like behavior in spontaneously breathing un-injured anesthetized rats (n = 8) with pacing electrodes implanted bilaterally in the diaphragm and external intercostal muscles, between 2nd and 3rd intercostal spaces. With this novel pacing system, we show that fatigability of the diaphragm was lower when using combined muscle stimulation than diaphragm stimulation alone (p = 0.014) and that combined muscle stimulation was able to induce sighs with significantly higher tidal volumes compared to diaphragm stimulation alone (p = 0.014). Our findings demonstrate that simultaneous activation of the inspiratory muscles could be used as a suitable strategy to delay stimulation-induced diaphragmatic fatigue and to induce a sigh-like behavior that could improve respiratory health.

An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

SEROPOSITIVE MYASTHENIA GRAVIS AS THE CAUSE OF MULTIPLE FAILED EXTUBATIONS AND A PROLONGED ICU STAY FOR COVID-19 PNEUMONIA: A CASE REPORT AND BRIEF LITERATURE REVIEW

SEROPOSITIVE MYASTHENIA GRAVIS AS THE CAUSE OF MULTIPLE FAILED EXTUBATIONS AND A PROLONGED ICU STAY FOR COVID-19 PNEUMONIA: A CASE REPORT AND BRIEF LITERATURE REVIEW

Diaphragm Dysfunction and Rehabilitation Strategy in Patients With Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) affects the whole body and causes many extrapulmonary adverse effects, amongst which diaphragm dysfunction is one of the prominent manifestations. Diaphragm dysfunction in patients with COPD is manifested as structural changes, such as diaphragm atrophy, single-fibre dysfunction, sarcomere injury and fibre type transformation, and functional changes such as muscle strength decline, endurance change, diaphragm fatigue, decreased diaphragm mobility, etc. Diaphragm dysfunction directly affects the respiratory efficiency of patients and is one of the important pathological mechanisms leading to progressive exacerbation of COPD and respiratory failure, which is closely related to disease mortality. At present, the possible mechanisms of diaphragm dysfunction in patients with COPD include systemic inflammation, oxidative stress, hyperinflation, chronic hypoxia and malnutrition. However, the specific mechanism of diaphragm dysfunction in COPD is still unclear, which, to some extent, increases the difficulty of treatment and rehabilitation. Therefore, on the basis of the review of changes in the structure and function of COPD diaphragm, the potential mechanism of diaphragm dysfunction in COPD was discussed, the current effective rehabilitation methods were also summarised in this paper. In order to provide direction reference and new ideas for the mechanism research and rehabilitation treatment of diaphragm dysfunction in COPD.

Sex, gender and the pulmonary physiology of exercise.

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.

Ultrasonographic assessment of diaphragmatic contraction and relaxation properties: correlations of diaphragmatic displacement with oesophageal and transdiaphragmatic pressure

Transdiaphragmatic (Pdi) and oesophageal pressures (Pes) are useful in understanding the pathophysiology of the respiratory system. They provide insight into respiratory drive, intrinsic positive end-expiratory pressure, diaphragmatic fatigue and weaning...