Respiratory Physiology & Neurobiology最新文献

Objective

This study compares two methods of citric acid-induced cough in guinea pigs in whole-body plethysmography (WBP) and double chamber plethysmography (DCP) to evaluate their efficacy.

Methods

Sixteen specific pathogen-free (SPF) and sixteen conventionally-bred (CON) animals were exposed to 0.4 M citric acid aerosol. They underwent cough provocation using both DCP and WBP methods. The number of coughs and latency to the first cough were recorded and analysed using statistical methods to determine significant differences between the two techniques.

Results

WBP resulted in significantly higher cough counts (WBP vs. DCP: 13±9 vs 2±3 for SPF; 14±8 vs 5±5 for CON; p<0.0001) and shorter latency (WBP vs. DCP: 59±6 s vs 159±14 s for SPF; 77±4 s vs 112±12 s for CON; p<0.0001) compared to DCP in both groups.

Conclusion

Methodological differences substantially impact cough responses. WBP provides a more reliable and physiologically relevant methodology for cough assessment, suggesting the need for standardized protocols in cough research to enhance translational relevance.

Intravenous rapid injection of fentanyl causes respiratory depression (severe apneas), leading to sudden death, which constitutes the deadliest drug reaction among overdoses of synthetic opioids. Here we asked whether acute inhalation of overdose fentanyl would also result in similar respiratory failure and death. The anesthetized and spontaneously breathing rats with tracheal cannulation were exposed to aerosolized fentanyl at 100 mg/m³ (FNT_H) or 30 mg/m³ (FNT_L) for 10 min. Minute ventilation (V_E), electromyography (EMG) of the internal and external intercostal muscles and thyroarytenoid muscles (EMG_II, EMG_EI, and EMG_TA), heart rate and arterial blood pressure were recorded. During the exposure, FNT_H and FNT_L immediately triggered bradypnea (40 % reduction, p < 0.05) with T_E prolonged and then gradually decreased V_E by 40 % (P < 0.05) after a brief V_E recovery. The initial T_E prolongation (apneas) were characterized by the cessation of EMG_EI activity with enhanced tonic discharges of EMG_TA and EMG_II. After termination of the exposure, the cardiorespiratory responses to FNT_L returned to the baseline values 30 min later, while those to FNT_H were greatly exacerbated (P < 0.05), leading to ventilatory and cardiac arrest occurred 16.4 ± 4.7 min and 19.3 ± 4.5 min respectively after the onset of FNT_H. The ventilatory arrest was featured by cessation of both EMG_EI and EMG_II and augmentation of tonic EMG_TA. Our results suggest that acute exposure to an overdose of fentanyl aerosol leads to death through initially inducing a brief central and upper airway obstructive apnea as well as chest wall rigidity followed by gradual severe hypoventilation, bradycardia and hypotension, and eventual cardiorespiratory arrest in anesthetized rats.

Background and methods

Little is known about self-induced cognitive trance (SICT) on respiratory function. The aims of this prospective, single-center, non-randomized, open-label study of healthy volunteers, were to characterize spirometry changes during SICT, confirm the safety of this technique, and investigate the potential clinical benefits of SICT.

Results

Nine people participated. There were no significant difference in FEV1 FVC or FEF 25–75 before, during, and after SICT. There were significant improvements in grip strength during SICT (+2.2 kg/5.7 %, p<0.05) and in self-efficacy score related to physical activity at the end of the trance. One participant had a significant worsening of FEV1 during SICT in the context of a recent upper airway infection.

Conclusion

SICT does not significantly modify spirometry data in healthy volunteers and can improve self-efficacy related to physical activity. SICT should probably be performed with caution during upper airway infections.

Intermittent hypoxia (IH) and intermittent transcutaneous electrical stimulation (ITES) might benefit patients with obstructive sleep apnea (OSA). However, the therapeutic value of combined IH and ITES in OSA is unknown. In this prospective, randomized, controlled crossover study, normoxia (air exposure for 50 min before sleep and sham stimulation for 6 h during sleep), IH (5 repeats of 5 min 10–12 % O₂ alternating with 5 min air for 50 min, and sham stimulation for 6 h), ITES (air exposure for 50 min and 6 repeats of 30 min transcutaneous electrical stimulation alternating with 30 min of sham stimulation for 6 h), and IH&ITES (10–12 % O₂ alternating with air for 50 min and transcutaneous electrical stimulation alternating with sham stimulation for 6 h) were administered to patients with OSA over four single-night sessions. The primary endpoint was difference in OSA severity between the interventions according to apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). The efficacy was response to IH, ITES, IH&ITES defined as a ≥50 % reduction in AHI compared with normoxia. Twenty participants (17 male, 3 female) completed the trial. The median (IQR) AHI decreased from 14.5 (10.8, 17.5) events/h with normoxia to 6.9 (3.9, 14.8) events/h with IH (p=0.020), 5.7 (3.4, 9.1) events/h with ITES (p=0.001), and 3.5 (1.8, 6.4) events/h with IH&ITES (p=0.001). AHI was significantly different between IH and IH&ITES (p=0.042) but not between ITES and IH&ITES (p=0.850). For mild-moderate OSA (n=17), IH, ITES, and IH&ITES had a significant effect on AHI (p=0.013, p=0.001, p=0.001, respectively) compared with normoxia, but there were no differences in post hoc pairwise comparisons between intervention groups. No serious adverse events were observed. In conclusion, IH, ITES, and IH&ITES significantly reduced OSA severity. IH&ITES showed better efficacy in mild-moderate OSA than IH and was comparable to ITES. Our data do not support recommending IH&ITES over ITES for OSA.

Assessing cough effectiveness, using Cough Peak Flow, is crucial for patients with Neuromuscular Diseases, such as Amyotrophic Lateral Sclerosis. Impaired cough function can contribute to respiratory decline and failure. The goal of the study is to determine the correlation between diaphragmatic excursion and cough expiratory phase, potentially utilizing ultrasonographic indices to estimate Cough Peak Flow in these patients. Twenty-two patients were enrolled in this study. The upward displacement of the diaphragm was measured with ultrasonography during voluntary cough expiration and Cough Peak Flow was simultaneously measured. A multivariable linear regression model was built to quantify the association between Cough Peak Flow and diaphragm expiratory excursion. There is significative relationship between Cough Peak Flow and diaphragm excursion with a Pearson’s r coefficient of 0.86 observed in the patients group. Multiple linear regression analysis for Cough Peak Flow (Adjusted R² = 0.86) revealed significant associations between Cough Peak Flow and expiratory excursion (adjusted β-coefficient: 64.78, 95 %, CI: 51.50–78.07, p<0.001) and sex (adjusted β-coefficient: −69.06; 95 % CI: −109.98 to −28.15, p=0.001). Our results predict the cough effectiveness by using M-mode diaphragmatic sonography with a potentially significant impact on therapeutic choices.

Objective

This study aimed to explore the influence of different spontaneous breathing trials (SBTs) on regional ventilation distribution in patients with prolonged mechanical ventilation (PMV).

Methods

A total of 24 patients with PMV were analyzed retrospectively. They received three different SBT modes which are automatic tube compensation (ATC), continuous positive airway pressure (CPAP), and T-piece (TP), over three days, and every SBT lasted two hours. Electrical impedance tomography (EIT) was used to monitor the SBT process and five-minute EIT data from five periods (pre-SBT which is t0, at the beginning and the end of the first hour SBT are t1 and t2, at the beginning and the end of the second hour SBT are t3 and t4) were analyzed.

Results

In all PMV patients, the temporal skew of aeration (TSA) values at t3 were significantly different in three SBTs (ATC: 18.18±22.97; CPAP: 20.42±17.01; TP:11.26±11.79; p=0.05). In the weaning success group, TSA (t1) values were significantly different too (ATC: 11.11±13.88; CPAP: 19.09±15.77; TP: 9.09±12.74; p=0.04). In the weaning failure group, TSA (t4) values were significantly different in three SBTs (ATC: 36.67±18.46; CPAP: 15.38±11.69; TP: 17.65±17.93; p=0.04). The patient’s inspiratory effort (Global flow index at t1) in patients with weaning failure under CPAP (3.51±4.31) was significantly higher than that in the ATC (1.15±1.47) and TP (0.89±1.28). The SBT mode with the best ventilation uniformity may be the one that activates the respiratory muscles the most which may be the optimal SBT. The SBT mode of most uniform ventilation distribution settings varies from patient to patient.

Conclusion

The regional ventilation distribution was different for each individual, making the SBT with the best ventilation distribution of patients need to be personalized. EIT is a tool that can be considered for real-time assessment.

Activity-related dyspnea in chronic lung disease is centrally related to dynamic (_dyn) inspiratory constraints to tidal volume expansion. Lack of reference values for exertional inspiratory reserve (IR) has limited the yield of cardiopulmonary exercise testing in exposing the underpinnings of this disabling symptom. One hundred fifty apparently healthy subjects (82 males) aged 40–85 underwent incremental cycle ergometry. Based on exercise inspiratory capacity (IC_dyn), we generated centile-based reference values for the following metrics of IR as a function of absolute ventilation: IR_dyn1 ([1-(tidal volume/IC_dyn)] x 100) and IR_dyn2 ([1-(end-inspiratory lung volume/total lung capacity] x 100). IR_dyn1 and IR_dyn2 standards were typically lower in females and older subjects (p<0.05 for sex and age versus ventilation interactions). Low IR_dyn1 and IR_dyn2 significantly predicted the burden of exertional dyspnea in both sexes (p<0.01). Using these sex and age-adjusted limits of reference, the clinician can adequately judge the presence and severity of abnormally low inspiratory reserves in dyspneic subjects undergoing cardiopulmonary exercise testing.

The goal of the current study was to identify the role of the glucocorticoids in the respiratory effects of proinflammatory cytokines. For this purpose intravenous injections of TNF-α were used in anesthetized spontaneously breathing rats before and after pretreatment of dexamethasone, a synthetic steroid with predominant glucocorticoid activity. Dexamethasone was injected intraperitoneally at a dose of 1 mg/kg. TNF-α was administrated into the tail vein at a dose of 40 mg/kg. We found that dexamethasone pretreatment eliminated the cytokine-induced increase in pulmonary ventilation and decrease in the hypoxic ventilatory response. Dexamethasone had a pronounced rapid effect on the respiratory activity of TNF-α as early as 30 minutes after administration. Therefore, we assume that this mechanism of action of dexamethasone was non-genomic, associated with the blocking of secondary mediators of the cytokine response.

Background

Long COVID is defined as persistency of symptoms, such as exertional dyspnea, twelve weeks after recovery from SARS-CoV-2 infection.

Objectives

To investigate ventilatory efficiency by the use of cardiopulmonary exercise testing (CPET) in patients with exertional dyspnea despite normal basal spirometry after 18 (T₁₈) and 36 months (T₃₆) from COVID-19 pneumonia.

Methods

One hundred patients with moderate-critical COVID-19 were prospectively enrolled in our Long COVID program. Medical history, physical examination and lung high-resolution computed tomography (HRCT) were obtained at hospitalization (T₀), 3 (T₃) and 15 months (T₁₅). All HRCTs were revised using a semi-quantitative CT severity score (CSS). Pulmonary function tests were obtained at T₃ and T₁₅. CPET was performed in a subset of patients with residual dyspnea (mMRC ≥ 1), at T₁₈ and at T₃₆.

Results

Remarkably, at CPET, ventilatory efficiency was reduced both at T₁₈ (V’_E/V’CO₂ slope = 31.4±3.9 SD) and T₃₆ (V’_E/V’CO₂ slope = 31.28±3.70 SD). Furthermore, we identified positive correlations between V’_E/V’CO₂ slope at T₁₈ and T₃₆ and both percentage of involvement and CSS at HRCT at T₀, T₃ and T₁₅. Also, negative linear correlations were found between V’_E/V’CO₂ slope at T₁₈ and T₃₆ and DL_CO at T₃ and T₁₅.

Conclusions

At eighteen months from COVID-19 pneumonia, 20 % of subjects still complains of exertional dyspnea. At CPET this may be explained by persistently reduced ventilatory efficiency, possibly related to the degree of lung parenchymal involvement in the acute phase of infection, likely reflecting a damage in the pulmonary circulation.

High-altitude environments present extreme conditions characterized by low barometric pressure and oxygen deficiency, which can disrupt brain functioning and cause edema formation. The objective of the present study is to investigate several biomolecule expressions and their role in the development of High Altitude Cerebral Edema in a rat model. Specifically, the study focuses on analyzing the changes in total arginase, nitric oxide, and lipid peroxidation (MDA) levels in the brain following acute hypobaric hypoxic exposure (7620 m, SO₂=8.1 %, for 24 h) along with the histopathological assessment. The histological examination revealed increased TNF-α activity, and an elevated number of mast cells in the brain, mainly in the hippocampus and cerebral cortex. The research findings demonstrated that acute hypobaric hypoxic causes increased levels of apoptotic cells, shrinkage, and swelling of neurons, accompanied by the formation of protein aggregation in the brain parenchyma. Additionally, the level of nitric oxide and MDA was found to have increased (p<0.0001), however, the level of arginase decreased indicating active lipid peroxidation and redox imbalance in the brain. This study provides insights into the pathogenesis of HACE by evaluating some biomolecules that play a pivotal role in the inflammatory response and the redox landscape in the brain. The findings could have significant implications for understanding the neuronal dysfunction and the pathological mechanisms underlying HACE development.