Respiratory Physiology & Neurobiology最新文献

Accumulation of reactive oxygen species during hyperoxia together with secondary bacteria-induced inflammation leads to lung damage in ventilated critically ill patients. Antioxidant N-acetylcysteine (NAC) in combination with surfactant may improve lung function. We compared the efficacy of NAC combined with surfactant in the double-hit model of lung injury. Bacterial lipopolysaccharide (LPS) instilled intratracheally and hyperoxia were used to induce lung injury in Wistar rats. Animals were mechanically ventilated and treated intravenously with NAC alone or in combination with intratracheal surfactant (poractant alfa; PSUR+NAC). Control received saline. Lung functions, inflammatory markers, oxidative damage, total white blood cell (WBC) count and lung oedema were evaluated during 4 hrs. Administration of NAC increased total antioxidant capacity (TAC) and decreased IL-6. This effect was potentiated by the combined administration of surfactant and NAC. In addition, PSUR+NAC reduced the levels of TNFα, IL-1ß, and TAC compared to NAC only and improved lung injury score. The combination of exogenous surfactant with NAC suppresses lung inflammation and oxidative stress in the experimental double-hit model of lung injury.

It is well-established that the brainstem is responsible for the automatic control of breathing, however, cortical areas control perception and conscious breathing. This study investigated activity in the prefrontal cortex (PFC) during breathing difficulty using functional near-infrared spectroscopy (fNIRS). It was hypothesized that extrinsic inspiratory loads will elicit regional changes in PFC activity and increased perception ratings, as a function of load magnitude and type. Participants were exposed to varying magnitudes of resistive (R) and pressure threshold (PT) inspiratory loads to increase breathing effort. Perception ratings of breathing effort and load magnitude were positively correlated (p < 0.05). PT loads were rated more effortful than R loads (p < 0.05). Differences in perceived effort were a function of inspiratory pressure-time-product (PTP) and inspiratory work of breathing (WoB). PFC activity increased with the largest PT load (p < 0.01), suggesting that the PFC is involved in processing respiratory stimuli. The results support the hypothesis that the PFC is an element of the neural network mediating effortful breathing perception.

The transient receptor potential (TRP) channels regulate physiological and pathological processes. Changes in their activity and sensitivity may be involved in the pathophysiology of asthma. The present study investigates the effect of an inhaled TRPV4 channel blocker HC-067047 in an experimental guinea pig model of ovalbumin-induced allergic asthma. We monitored the effect of 50 nM, 100 nM, and 150 nM HC-067047 concentrations on airway defense reflexes in vivo and tracheal smooth muscle contractility in vitro. The anti-inflammatory action of HC-067047 was investigated by analysis of chronic inflammation markers from lung homogenates. The results suggest that HC-067047 can suppress airway defense reflexes in vivo and acetylcholine-induced contractility in vitro. Immunological analysis revealed that TRPV4 channel blockade leads to a decrease in the levels of inflammatory cytokines. An effect on airway defence reflexes and airway inflammation was observed using tested concentrations (50 mM, 100 mM, 150 mM) of HC-067047. The effects of HC-067047 on both airway defense reflexes and inflammation underline the role of TRPV4 channels in asthma and uncover therapeutic targets for developing innovative drugs in asthma therapy.

Intrapulmonary percussive ventilation (IPV) has been postulated to enhance mucociliary clearance by improving tracheobronchial sputum rheological properties. The IPV effects on linear (viscoelasticity) and non-linear (flowing) rheological properties of 40 sputum samples collected from 19 patients with muco-obstructive lung diseases were investigated ex-vivo. Each sputum sample was split into 4 aliquots. These aliquots were independently placed in a circuit connected on one side to an IPV device and on the other side to a lung model that simulated spontaneous adult breaths. IPV was superimposed on simulated breathing. Three aliquots were exposed to a different IPV setting, modifying either percussion frequency or amplitude (4 Hz-200 L/min, 10 Hz-200 L/min, 10 Hz-140 L/min). One aliquot was only exposed to breathing (IPV was switched off, control condition). Each aliquot underwent 5 min of the pre-fixed mechanical stimulation before being recollected to proceed to rheological analysis. Neither percussion frequencies nor amplitudes had a significant impact on any sputum rheological properties studied. These results need to be confirmed in vivo.

Heart rate variability (HRV) as an index of cardiac autonomic control in acute lung injury (ALI) has been evaluated in anaesthetized rats intratracheally instilled with bacterial lipopolysaccharide (LPS) and ventilated with breathing frequency of 60/min, 40% oxygen, inspiratory time 40%, tidal volume of 6 mL/kg. ECG was recorded before and 30, 60, 120, 180 and 240 min after LPS or saline (control) administration. HRV was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD and spectral power in high frequency (HF) band. Lactate in plasma, and oxidative stress, IL-1β, IL-5, IL-12p70 and IL-13 and galectin-3 in heart tissue raised in LPS-injured rats. Overall HRV magnitude (SDRR) and marker of vagal heart rate control (RMSSD), as well as frequency domain parameter, spectral power HF was increased 120 and 180 min since ALI onset. In conclusion, LPS-induced ALI is accompanied by altered vagal cardiac control mediated by autonomic nervous system, likely based on the close relationship between immune response and vagally mediated autonomic nervous activity.

Oscillometry has been around for almost 70 years, but there are still many unknowns. The test is performed during tidal breathing and is therefore free from patient-dependent factors that could influence the results. The Forced Oscillation Technique (FOT), which requires minimal patient cooperation, is gaining ground, particularly with elderly patients and children. In pulmonology, it is a valuable tool for assessing obstructive conditions (with a distinction between central and peripheral obstruction) and restrictive disorders (intrapulmonary and extrapulmonary). Its sensitivity allows the assessment of bronchodilator and bronchoconstrictor responses. Different lung diseases show different patterns of changes in FOT, especially studied in asthma and chronic obstructive pulmonary disease. Because of these differences, many studies have analysed the usefulness of this technique in different areas of medicine. In this paper, the authors would like to present the basics of oscillometry with the areas of its most recent clinical applications.

In pulmonary surfactant (PS) the coexistence of the ordered (Lo) and disordered (Ld) lipid phases would be essential for an optimal activity. Electron spin resonance (ESR) of PS labeled with 5-doxil stearic acid shows two spectral components called S and W. S/W ratio could be understood as the ratio between the probe population in Lo and in Ld. Although the specificity of S/W as an indicator of Lo/Ld has not yet been demonstrated, S/W has been used qualitatively to study changes in Lo/Ld. The goal of this paper is to stablish the correlation between S/W parameter and the amount of lipids in Ld (%Ld) measured by the ESR TEMPO technique described in our previous work.

S/W and %Ld were measured in different PS samples under different experimental conditions. The results showed an inverse correlation between S/W and %Ld (r = −0.983; p < 0.001). We demonstrated that the S/W is sensible to the changes of Lo/Ld and can be used to quantify the %Ld.

Vagal sensory inputs to the brainstem can alter breathing through the modulation of pontomedullary respiratory circuits. In this study, we set out to investigate the localised effects of modulating lateral parabrachial nucleus (LPB) activity on vagally-evoked changes in breathing pattern. In isoflurane-anaesthetised and instrumented mice, electrical stimulation of the vagus nerve (eVNS) produced stimulation frequency-dependent changes in diaphragm electromyograph (dEMG) activity with an evoked tachypnoea and apnoea at low and high stimulation frequencies, respectively. Muscimol microinjections into the LPB significantly attenuated eVNS-evoked respiratory rate responses. Notably, muscimol injections reaching the caudal LPB, previously unrecognised for respiratory modulation, potently modulated eVNS-evoked apnoea, whilst muscimol injections reaching the intermediate LPB selectively modulated the eVNS-evoked tachypnoea. The effects of muscimol on eVNS-evoked breathing rate changes occurred without altering basal eupneic breathing. These results highlight novel roles for the LPB in regulating vagally-evoked respiratory reflexes.

Many studies have been conducted in the search for the mechanism underlying CNS-oxygen toxicity (OT), which may be fatal when diving with a closed-circuit apparatus. We investigated the influence of hyperbaric oxygen (HBO) on blood glucose level (BGL) in Mn-superoxide dismutase (SOD2) knockdown mice regarding CNS-OT in particular under stress conditions such as hypoglycemia or hyperglycemia. Two groups of mice were used: SOD2 knockdown (Heterozygous, HET) mice and their WT family littermates. Animals were exposed to HBO from 2 up to 5 atmosphere absolute (ATA). Blood samples were drawn before and after each exposure for measurement of BGL. The mice were sacrificed following the final exposure, which was at 5 ATA. We used RT-PCR and Western blot to measure levels of glucose transporter 1 (GLUT1) and hypoxia inducible factor (HIF)1a in the cortex and hippocampus. In the hypoglycemic condition, the HET mice were more sensitive to oxidative stress than the WT. In addition, following exposure to sub-toxic HBO, which does not induce CNS-OT, BGL were higher in the HET mice compared with the WT. The expression of mRNA of GLUT1 and HIF-1a decreased in the hippocampus in the HET mice, while the protein level decreased in the HET and WT following HBO exposure. The results suggest that the higher BGL following HBO exposure especially at SOD2 HET mice is in part due to reduction in GLUT1 as a consequence of lower HIF-1a expression. This may add part to the puzzle of the understanding the mechanism leading to CNS-OT.

The study aimed to identify whether pelvic floor muscles modulate length with breathing, and if any length changes induced by breathing relate to abdominal cavity displacement and intra-abdominal pressure. To investigate these relationships, displacement of pelvic landmarks that related to pelvic floor muscle length using transperineal ultrasound imaging, breath volume, intra-abdominal pressure, abdominal and ribcage displacement, and abdominal and anal sphincter muscle electromyography were measured during quiet breathing and breathing with increased dead-space in ten healthy men. Pelvic floor muscle landmark displacement modulated with ribcage motion during breathing. This relationship was stronger for: i) motion of the urethrovesical junction (puborectalis muscle length change) than the mid-urethra landmark (striated urethral sphincter muscle length change), and ii) dead-space breathing in standing than dead-space breathing in supine or quiet breathing in standing. In most (but not all) participants, the urethrovesical junction descended during inspiration and elevated during expiration. Striated urethral sphincter length changes during the respiratory cycle was independent of intra-abdominal pressure. In summary, breathing involves pelvic floor muscle length changes and is consistent with the role of these muscles during respiration to aid maintenance of continence, lung ventilation and/or provision of support to the abdominal cavity. Clinicians who train pelvic floor muscles need to be aware that length change of pelvic floor muscles is expected with breathing.