Respiratory Physiology & Neurobiology最新文献

Introduction

The interaction between the cardiovascular and respiratory systems in healthy subjects is determined by the autonomic nervous system and reflected in respiratory sinus arrhythmia. Recently, another pattern of cardio-respiratory coupling (CRC) has been proposed linking synchronization of heart and respiratory system. However, CRC has not been studied precisely in heart failure (HF) with reduced ejection fraction (EF) (HFrEF) according to the myocardial recovery.

Methods

10-min resting electrocardiography measurements were performed in persistent HFrEF patients (n=40) who had a subsequent left ventricular EF (LVEF) of ≤ 40 %, HF with recovered EF patients (HFrecEF) (n=41) who had a subsequent LVEF of > 40 % and healthy controls (n=40). Respiratory frequency, respiratory rate, CRC index, time-domain, frequency-domain and nonlinear heart rate variability indices were obtained using standardized software-Kubios™. CRC index was defined as respiratory high-frequency peak minus heart rate variability high-frequency peak.

Results

Respiratory rate was positively correlated with high-frequency (HF) peak (Hz) in both persistent HFrEF group (p<0.001) and HFrecEF group (p<0.001), while respiratory rate was negatively correlated with HF power (ms²) in the healthy controls (p<0.05). CRC index was lowest in the persistent HFrEF group followed by HFrecEF and was high in healthy controls (0.008 vs 0.012 vs 0.056 Hz, p=0.03).

Conclusion

CRC index was lowest in patients with impaired myocardial recovery, which indicates that cardio-respiratory synchrony is stronger in persistent HFrEF. This may represent a higher HF peak (Hz)/lower HF power (ms²) and abnormal sympathovagal balance in persistent HFrEF group compared to healthy controls. Further work is underway to tests this hypothesis and determine the utility of CRC index in HF phenotypes and its utility as a potential biomarker of response with neuromodulation.

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the methyl-CPG-binding protein 2 (Mecp2) gene. Frequent apneas and irregular breathing are prevalent in RTT, and also occur in rodent models of the disorder, including Mecp2^Bird and Mecp2^R168X mice. Sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT (Abdala et al., 2014). Targeting the 5HT1a receptor alone also improves respiration in RTT mice (Levitt et al., 2013). However, the contribution of D2-like receptors in correcting these respiratory disturbances remains untested. PAOPA, a dopamine D2-like receptor positive allosteric modulator, and quinpirole, a dopamine D2-like receptor orthosteric agonist, were used in conjunction with whole-body plethysmography to evaluate whether activation of D2-like receptors is sufficient to improve breathing disturbances in female heterozygous Mecp2^Bird/+ and Mecp2^R168X/+ mice. PAOPA did not significantly change apnea incidence or irregularity score in RTT mice. PAOPA also had no effect on the ventilatory response to hypercapnia (7 % CO₂). In contrast, quinpirole reduced apnea incidence and irregularity scores and improved the hypercapnic ventilatory response in Mecp2^R168X/+ and Mecp2^Bird/+ mice, while also reducing respiratory rate. These results suggest that D2-like receptors could contribute to the positive effects of sarizotan in the correction of respiratory abnormalities in Rett syndrome. However, positive allosteric modulation of D2-like receptors alone was not sufficient to evoke these effects.

Introduction

Dissolved-phase ¹²⁹Xe MRI metrics suggest that gas diffusion may be more compromised at submaximal lung inflation compared to maximal inflation. We hypothesized that this diffusion deficit could be detected by comparing the carbon monoxide transfer coefficient (Kco) at submaximal lung inflation to that measured routinely at total lung capacity (TLC).

Methods

Asthma and COPD patients performed carbon monoxide diffusion tests, first at maximal lung inflation for routine Kco and alveolar volume VA and then, at a 30 % reduced inflation (redux; obtaining Kco_redux and VA_redux). At both inflations mixing efficiency was determined as VA/TLC and VA_redux/TLC_redux to examine a potential effect on Kco_redux/Kco behavior.

Results

In normal subjects (n=36), median Kco_redux/Kco amounted to 130 [IQR:122–136]% as expected for normal Kco recruitment response. However, 60 % of asthma patients (49/83) and 80 % of COPD patients (44/55) showed reduced Kco recruitment at submaximal inflation (Kco_redux/Kco<122 %). In the asthma group, with otherwise normal routine Kco, Kco_redux/Kco was significantly correlated with RV/TLC ratio (r=-0.53;P<0.001), but not with VA/TLC. In COPD patients, all with abnormal routine Kco, abnormal Kco_redux/Kco response occurred in those patients with lower FEV₁, higher RV/TLC and lower VA/TLC (P<0.01 for all).

Conclusion

Sizeable portions of COPD and asthma patients showed a lack of normal Kco recruitment at submaximal lung inflation, related to high RV/TLC. In asthma, this was the case despite normal Kco at full lung inflation, suggesting that hyperinflation at lung volumes less than TLC affects the carbon monoxide diffusion rate constant by distorting pulmonary capillaries and alveolar–capillary membranes.

The airway epithelium is located at the interactional boundary between the external and internal environments of the organism and is often exposed to harmful environmental stimuli. Inflammatory response that occurs after airway epithelial stress is the basis of many lung and systemic diseases. Chloride intracellular channel 4 (CLIC4) is abundantly expressed in epithelial cells. The purpose of this study was to investigate whether CLIC4 is involved in the regulation of lipopolysaccharide (LPS)-induced inflammatory response in airway epithelial cells and to clarify its potential mechanism. Our results showed that LPS induced inflammatory response and decreased CLIC4 levels in vivo and in vitro. CLIC4 silencing aggravated the inflammatory response in epithelial cells, while overexpression of CLIC4 combined with LPS exposure significantly decreased the inflammatory response compared with cells exposed to LPS without CLIC4 overexpression. By labeling intracellular chloride ions with chloride fluorescent probe MQAE, we showed that CLIC4 mediated intracellular chloride ion-regulated LPS-induced cellular inflammatory response.

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.