Respiratory Physiology & Neurobiology最新文献

Background

The forced oscillation technique (FOT) enables non-invasive measurement of respiratory system impedance. Limited data exists on how changes in operating lung volume (OLV) impact FOT-derived measures of airway resistance (Rrs) and reactance (Xrs).

Objectives

This study examined the reproducibility and responsiveness of FOT-derived measures of Rrs and Xrs during simulated changes in OLV.

Methods

Participants simulated breathing at six OLVs: total lung capacity (TLC), ∼50% of inspiratory reserve volume (IRV₅₀), ∼two-times tidal volume (VT₂), tidal volume (VT), ∼50% of expiratory reserve volume (ERV₅₀), and residual volume (RV), on a commercially available FOT device. Each simulated OLV manuever was performed in triplicate and in random order. Total Rrs and Xrs were recorded at 5, 11, and 19 Hz.

Results

Twelve healthy participants (2 female) completed the study (weight: 76.5 ± 13.6 kg, height: 178.6 ± 9.7 cm, body mass index: 23.9 ± 3.1 kg/m²). Reproducibility of Rrs and Xrs at VT, VT₂ and IRV₅₀ was good to excellent (Range: ICC: 0.89–0.98, 95% confidence interval (CI): 0.70–0.98), while reproducibility at TLC, RV, and ERV₅₀ was poor to excellent (Range: ICC: 0.60–0.98, 95% CI: 0.36–0.97). Rrs and Xrs were not different between VT and VT₂ at any frequency (P > .05). With lung hyperinflation from VT to TLC, Rrs and Xrs decreased at all three frequencies (e.g., At 5 Hz Rrs: mean difference (MD): − 0.89, 95%CI: − 0.03 to − 1.75, P = .04; Xrs: MD: − 0.56, 95%CI: − 0.25 to − 0.86, P < .01). With lung hypoinflated from VT to RV, Rrs increased, and Xrs decreased for all frequencies (e.g., MD at 5 Hz, Rrs: MD: 2.31, 95%CI: 0.94–3.67, P < .01; Xrs: MD: −2.53, 95%CI: −4.02 to −1.04, P < .01).

Conclusion

FOT-derived measures of airway Rrs and Xrs are reproducible across a range of OLV’s, and are responsive to hyper- and hypo-inflation of the lung. To further understand the impact of lung hyper- and hypo-inflation on FOT-derived airway impedance additional study is required in individuals with pathological variations in operating lung volume.

Purpose

To investigate the correlation between volume of carbon dioxide elimination (V̇CO₂) and end-tidal carbon dioxide (PETCO₂) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model.

Methods

Respiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion.

Results

Prior to ARDS induction, mean (SD) CO, V̇CO₂, PETCO₂, and dead space to tidal volume ratio (V_d/V_t) were 4.16 (1.10) L/min, 103.69 (18.06) ml/min, 40.72 (3.88) mmHg and 0.25 (0.09) respectively. Partial correlation coefficients between average CO, V̇CO₂, and PETCO₂ were 0.44 (95% confidence interval: 0.18–0.69) and 0.50 (0.18–0.74), respectively. After ARDS induction, mean CO, V̇CO₂, PETCO₂, and V_d/V_t were 3.33 (0.97) L/min, 113.71 (22.97) ml/min, 50.17 (9.73) mmHg and 0.40 (0.08). Partial correlations between CO and V̇CO₂ was 0.01 (−0.31 to 0.37) and between CO and PETCO₂ was 0.35 (−0.002 to 0.65).

Conclusion

ARDS may limit the utility of volumetric capnography to monitor CO.

Purpose

To determine the association between exercise capacity based on peak oxygen uptake (VO_2peak) and resting cardiorespiratory coupling (CRC) levels in athletes and non-athletes’ subjects.

Methods

A cross-sectional study was carried out in 42 apparently healthy male subjects, aged between 20 and 40 years old. The participants were allocated into athletes (n = 21) and non-athletes (n = 21) groups. Resting electrocardiogram and respiratory movement (RESP) were simultaneously acquired during 15 min in supine position and quiet breathing. The beat-to-beat heart period (HP) and RESP series were determined from the recorded signals. Traditional analysis of HP based on frequency domain indexes was performed considering the high-frequency (0.15 – 0.45 Hz) components. To compute the CRC, the linear association between HP and RESP series was determined via squared coherence function and directionality of interaction was investigated through the causal extension of this approach. The exercise capacity was assessed through incremental cardiopulmonary exercise testing in order to determine the VO_2peak.

Results

Traditional analysis of HP based on high-frequency index was not correlated with exercise capacity in the athletes (r = −0.1, p = 0.5) and non-athletes (r = −0.1, p = 0.3) cohorts. However, resting CRC values was associated with exercise capacity in athletes (r = 0.4, p = 0.03), but not in the non-athletes group (r = −0.2, p = 0.3).

Conclusion

These results suggest that improved resting values of CRC is associated with higher exercise capacity (VO_2peak) in endurance athletes. Moreover, frequency domain of HP was not sensitive to identifying this relationship, probably because effects of training on parasympathetic modulation might be affected by respiratory dynamics, and this influence has a directionality (i.e., from RESP to HP).

Breathing requires distinct patterns of neuronal activity in the brainstem. The most critical part of the neuronal network responsible for respiratory rhythm generation is the preBötzinger Complex (preBötC), located in the ventrolateral medulla. This area contains both rhythmogenic glutamatergic neurons and also a high number of inhibitory neurons. Here, we aimed to analyze the activity of glycinergic neurons in the preBötC in anesthetized mice. To identify inhibitory neurons, we used a transgenic mouse line that allows expression of Channelrhodopsin 2 in glycinergic neurons. Using juxtacellular recordings and optogenetic activation via a single recording electrode, we were able to identify neurons as inhibitory and define their activity pattern in relation to the breathing rhythm. We could show that the activity pattern of glycinergic respiratory neurons in the preBötC was heterogeneous. Interestingly, only a minority of the identified glycinergic neurons showed a clear phase-locked activity pattern in every respiratory cycle. Taken together, we could show that neuron identification is possible by a combination of juxtacellular recordings and optogenetic activation via a single recording electrode.

In the elderly, airway infections are associated with impaired airway defense behaviors, leading to an increased risk of airway infection. The muscles of the chest and abdominal wall are essential for performing effective airway defense manoeuvres, however, very little is known about their function in aging. Here in the 6- and 24-months old Fischer 344 rat model of aging, we assess the contractility and fatigability of chest (the pectoralis major muscle) and abdominal wall (external abdominal oblique) muscles. We assessed muscle function using an ex vivo approach, measuring isometric specific forces normalised to muscle CSA, via a platinum plate field stimulations at a range of frequencies (5–150 Hz) for 1 s. Surprisingly, we did not observe any effect of age on the specific force and fatigue properties of the pectoral muscle. However, in 24-months old rats, EAO specific force was reduced by ∼32 %. These finding suggest that not all respiratory muscles are equally vulnerable to age-associated weakness.

Low level activation of mu-opioid receptors (MORs) in neonatal rat brainstem-spinal cord preparations increases inspiratory burst amplitude recorded on cervical spinal roots. We tested whether: (1) MOR activation with an endogenous ligand, such as endomorphin-2, increases inspiratory burst amplitude, (2) disinhibition of GABAergic or glycinergic inhibitory synaptic transmission is involved, and (3) inflammation alters endomorphin-2 effects. Using neonatal rat (P0-P3) brainstem-spinal cord preparations, bath-applied endomorphin-2 (10–200 nM) increased inspiratory burst amplitude and decreased burst frequency. Blockade of GABAA receptors (picrotoxin), glycine receptors (strychnine), or both (picrotoxin and strychnine) did not abolish endomorphin-2-induced effects. In preparations isolated from neonatal rats injected 3 h previously with lipopolysaccharide (LPS, 0.1 mg/kg), endomorphin-2 continued to decrease burst frequency but abolished the burst amplitude increase. Collectively, these data indicate that disinhibition of inhibitory synaptic transmission is unlikely to play a role in endomorphin-2-induced changes in inspiratory motor output, and that different mechanisms underlie the endomorphin-2-induced increases in inspiratory burst amplitude and decreases in burst frequency.

Acute, intermittent hypoxia (AIH) induces ventilatory long-term facilitation (vLTF) in awake, freely behaving rats under poikilocapnic and isocapnic experimental conditions. Establishing pre-clinical methods for vLTF induction that more closely align with successful protocols in humans and anesthetized rats would minimize dissonance in experimental findings and improve translational aspects of vLTF. Here, we tested several levels of low-dose CO₂ supplementation during and after AIH to determine 1) the lowest amount of inspired CO₂ that would maintain isocapnia in rats during a vLTF protocol, and 2) the net impact of supplemental CO₂ on vLTF expression. Rats received one of four levels of inspired CO₂ (0%, 0.5%, 1% or 2%) administered during AIH and for the 60 min following AIH to quantify vLTF. Our findings indicated that 2% inspired CO₂ was sufficient to maintain isocapnia across the AIH protocol and reveal significant vLTF. These findings provide evidence-based support for using 2% supplemental CO₂ during and after AIH when assessing vLTF in rats.

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation long-term. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426–21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL-ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence.