Expiratory Duration Research Articles

Glutamatergic and purinergic transmitters and astrocyte modulation in the synaptic transmission in the NTS of rats exposed to short-term sustained hypoxia.

There is evidence that astrocytes modulate synaptic transmission in the nucleus tractus solitarius (NTS) interacting with glutamatergic and purinergic mechanisms. Here, using in situ working heart-brainstem preparations, we evaluated the involvement of astrocyte and glutamatergic/purinergic neurotransmission in the processing of autonomic and respiratory pathways in the NTS of control and rats exposed to sustained hypoxia (SH). Baseline autonomic and respiratory activities and the responses to chemoreflex activation (KCN) were evaluated before and after microinjections of fluorocitrate (FCt, an astrocyte metabolic inhibitor), kynurenic acid, and pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS) (nonselective antagonists of glutamatergic and purinergic receptors) into the rostral aspect of the caudal commissural NTS. FCt had no effects on the baseline parameters evaluated but reduced the bradycardic response to chemoreflex activation in SH rats. FCt combined with kynurenic acid and PPADS in control rats reduced the baseline duration of expiration, which was attenuated after SH. FCt produced a large increase in PN frequency discharge in control rats, which was reduced after SH, indicating a reduction in the astrocyte modulation after SH. The data show that 1) the bradycardic component of the peripheral chemoreflex is reduced in SH rats after astrocytes inhibition, 2) the inhibition of astrocytes in the presence of double antagonists in the NTS affects the modulation of baseline duration of expiration in control but not in SH rats, and 3) the autonomic and respiratory responses to chemoreflex activation are mediated by glutamatergic and purinergic receptors in the rostral aspect of the caudal commissural NTS.NEW & NOTEWORTHY Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats.

Diagnosis of patients with chronic heart failure implementing wavelet transform and machine learning techniques

Chronic heart failure (CHF) is a significant public health concern due to its increasing prevalence, high number of hospital admissions, and associated mortality. Its prevalence is progressively increasing due to the aging of the population and the decrease in mortality from acute myocardial infarction, among other medical advancements. Consequently, the incidence of CHF predominantly affects older age groups, doubling its prevalence every decade, becoming one of the main causes of mortality in patients older than 65 years. The main objective of this study is to apply machine learning based techniques to determine the best models to classify patients with chronic heart failure through their respiratory pattern. These patterns have been characterized from time series such as inspiratory and expiratory times, breathing duration, and tidal volume obtained from the respiratory flow signal. Based on the behavior of the respiratory pattern, CHF patients were classified into patients with non-periodic breathing, with periodic breathing, and with Cheyene-Stokes respiration (CSR). Time-frequency and statistical techniques have been implemented to analyze these features, and then various classification methods have been applied to define the optimal model with the best accuracy rates. These models could help to better understand the evolution of this disease and in early diagnosis.

Percent duration of heart rate acceleration within the respiratory cycle: a novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes. The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 s. A 5-min R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthened when TE increased but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.NEW & NOTEWORTHY In healthy adults who regulated their breathing across nine combinations of inspiration and expiration durations, we used averaged pattern waveform technique to quantify the durations of heart rate acceleration and deceleration within the respiratory cycle. The percent duration of acceleration showed a strong correlation with traditional heart rate asymmetry indexes, which evaluate the magnitude and number of beat-to-beat changes. This new approach opens a window to explore the asymmetric features of heart rate variability.

Wearing surgical face mask has no significant impact on auscultation assessment.

During the COVID-19 pandemic, universal mask-wearing became one of the main public health interventions. Because of this, most physical examinations, including lung auscultation, were done while patients were wearing surgical face masks. The aim of this study was to investigate whether mask wearing has an impact on pulmonologist assessment during auscultation of the lungs. This was a repeated measures crossover design study. Three pulmonologists were instructed to auscultate patients with previously verified prolonged expiration, wheezing, or crackles while patients were wearing or not wearing masks (physician and patients were separated by an opaque barrier). As a measure of pulmonologists' agreement in the assessment of lung sounds, we used Fleiss kappa (K). There was no significant difference in agreement on physician assessment of lung sounds in all three categories (normal lung sound, duration of expiration, and adventitious lung sound) whether the patient was wearing a mask or not, but there were significant differences among pulmonologists when it came to agreement of lung sound assessment. Clinicians and health professionals are safer from respiratory infections when they are wearing masks, and patients should be encouraged to wear masks because our research proved no significant difference in agreement on pulmonologists' assessment of auscultated lung sounds whether or not patients wore masks.

Exploring Serotonergic mechanisms in Opioid Induced Respiratory Depression

Opioids profoundly depress breathing which can be fatal in the case of overdose. Despite growing knowledge of the pontine and medullary respiratory control circuits that are inhibited by opioids, the circuit and cellular mechanisms of opioid induced respiratory depression are not fully understood. Serotonin neurons located in the caudal medullary raphe modulate breathing and possess mu opioid receptors. Therefore, we hypothesized that serotonin-producing raphe neurons contribute to opioid induced respiratory depression. To test this, we employed to experimental approaches: 1) arterially perfused in situ working heart brainstem preparations and 2) ex vivo acute brain slice electrophysiology to identify and characterize serotonin neuron inputs onto brainstem respiratory neurons. To specifically activate serotonin neurons, we used ePet-Cre::Ai32 mice which Cre-dependently express channelrhodopsin-2, a light-activated cation channel, in serotonin neurons. At the circuit level, using the in situ preparation, we found that activation of caudal medullary raphe serotonin neurons increased respiratory rate by decreasing inspiratory and expiratory duration. Fentanyl application blocked the respiratory effects induced by serotonin neuron activation which were subsequently restored using naloxone. These results suggest serotonin neurons in the caudal medullary raphe are inhibited by opioids. To characterize the serotonin-mediated mechanisms at the cellular level, we made acute brain slices containing dorsal raphe neurons and lateral parabrachial neurons from ePet-Cre::Ai32 mice. We verified that optical stimulation resulted in action potentials and serotonin release from dorsal raphe serotonin neurons. Optically evoked serotonin release caused 5HT1A receptor-mediated outward currents in dorsal raphe serotonin neurons. To locate and characterize serotonin neuron inputs onto lateral parabrachial neurons, we performed whole-cell voltage clamp recordings from lateral parabrachial neurons and delivered paired light pulses (10 ms duration, 50 ms interval). We observed optically evoked inhibitory post-synaptic currents (IPSCs) that were blocked by the GABA-A receptor antagonist gabazine (1 μM). Optically evoked IPSCs had long latency (&gt; 5 ms) and high jitter (&gt; 1 ms), indicating stimulation of serotonin terminals resulted in polysynaptic GABA release onto lateral parabrachial neurons. Future work will examine the influence of opioids on this raphe-parabrachial circuit. Uncovering the role of serotonin neurons in opioid induced respiratory depression may reveal targets for restoring breathing in the presence of opioids or other conditions where life-threatening apneas occur. This work was supported by the National Institutes of Health (NIDA) R01DA047978-05 grant to ESL. 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.

The effect of the lateral hypothalamic leptin circuit on cardiorespiratory control

In addition to its well-known roles in regulating metabolic homeostasis, leptin signaling in the brain has also been critically involved in cardiovascular and respiration functions. Although the central mechanisms mediating leptin’s effect on metabolic control have been extensively studied and elucidated, the neural substrates by which leptin exert its effect on cardiovascular and respiratory functions remain incompletely understood. Leptin receptors (LepRs) are expressed distinct hypothalamic nuclei, including the lateral hypothalamic area (LHA), a brain region historically known as the “feeding center”. We recently performed anterograde tract-tracing of LHA LepR-positive neurons and observed a broad but regionally enriched pattern of projections throughout the brain, including, but not limited to the brain regions involved in sympathetic control of cardiovascular function and breathing, such as the periaqueductal gray and ventrolateral medullar. Based on these preliminary neuroanatomical observations, we hypothesized that the LHA leptin circuit is critically involved in cardiorespiratory control. To test this hypothesis, we generated mice expressing hM3Dq-mCherry or mCherry (control) specifically in LHA LepR+ neurons by performing stereotaxic microinjection of Cre-dependent AAV-DIO-hM3Dq-mCherry or AAV-DIO-mCherry into the LHA of LepR-Cre+ mice. These mice were then subjected to radiotelemetry recording of blood pressure and whole-body plethysmography to evaluate the respiratory function. We found that chemogenetic activation of LHA LepR+ neurons by intraperitoneal injection of deschloroclozapine (DCZ, 0.5 mg/Kg) significantly elevated blood pressure (p&lt;0.01) and heart rate (p&lt;0.01) independently of locomotor activity. Whole-body plethysmography further revealed that activation of LHA LepR+ neurons also drastically increased the respiratory rate (p&lt;0.0001) and minute ventilation (p&lt;0.001) without a significant change in the tidal volume. Increased respiratory rate was associated with shortening both inspiratory and expiratory durations. These results identify the LHA as a novel hypothalamic node through which the circulating metabolic hormone leptin might influence cardiorespiratory control. This work is supported by the grants from the National Institute of Health (HL127673 and HL153274 to HC). 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.

Changes in preBötzinger Complex neuron discharge associated with changes in PCO2 in decerebrate rabbits

Background: Maskrey and Nicol reported a strong increase in minute ventilation with increase in PCO2 (J Physiol 1980, 301: 49-58). We investigated a) whether there was a ceiling to this effect at high CO2 levels and b) whether the change in ventilation was associated with specific changes in respiratory neurons in the preBötzinger complex (preBC). Methods: The study was approved by the local Animal Care Committee and conformed to NIH standards. Adult New Zealand White rabbits (3-4 kg) were anesthetized, tracheotomized, ventilated, decerebrated and vagotomized. Phrenic nerve activity was recorded from the C5 rootlet, time averaged and used to calculate inspiratory (TI) and expiratory durations (TE) and peak phrenic activity (PPA). PPA was normalized to the value at PCO2 50mmHg. Individual neurons were recorded in the functionally identified preBC using multichannel electrodes at increasing CO2 levels. Statistical analysis used the Wilcoxon signed-rank test to determine changes in respiratory parameters between CO2 levels and Friedman RM-ANOVA to determine changes in neuronal discharge frequency (Fn). A generalized linear mixed model was used to determine associations between CO2-dependent changes in TI, TE, PPA, and changes in Fn for different neuron types. p&lt;0.05 indicated a significant difference. Results: In 34 animals, the increase in minute ventilation with increasing PCO2 was due mostly to the change in PPA. The increase in respiratory rate was due mostly to a decrease in TE. There was little increase in respiratory output at PCO2 &gt; 50 mmHg. In 209 neurons, increasing PCO2 increased Fn in inspiratory augmenting (I aug, n= 70, p&lt;0.0001 for CO2 30 vs 40 and 40 vs 50mmHg), I parabolic (I para, n=43, p&lt;0.0001 for CO2 40 vs 50 mmHg), pre-inspiratory (pre-I, n=35, p&lt;0.01 for CO2 30 vs 40 mmHg), and expiratory decrementing (E dec, n=44, p&lt;0.01 for CO2 40 vs 50 mmHg) neurons, but not in I dec (n=8) and non-respiratory modulated (NRM, n=9) neurons. The strongest correlation was found between the changes in phase timing and PPA and Fn in I aug and pre-I neurons. Conclusion: We found a ceiling effect to the increase in respiratory output at PCO2 levels &gt; 50 mmHg. Inspiratory preBC neuron subtypes were more affected by the changes in PCO2. NIH R01HL159546. 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.

Inhibition of glutamatergic interneurons of the lateral parafacial region of mice attenuates the ventilatory response to hypercapnia

The lateral parafacial region (pFL) generates the expiratory motor activity during hypercapnia. It was demonstrated that this region contains excitatory neurons and interneurons (with local projections), with a population of glutamatergic neurons that are silent under resting conditions, but become active at the end of expiration, simultaneously with active expiration, in response to hypercapnia/acidosis. However, the role of pFL glutamatergic interneurons in regulating pulmonary ventilation during hypercapnia is unclear. Herein, we hypothesized that the inhibition of pFL glutamatergic interneurons attenuates the ventilatory responses to hypercapnia. Therefore, we evaluated the effects of the chemogenetic inhibition of pFL glutamatergic interneurons of non-anesthetized mice on ventilatory parameters during resting and hypercapnia. We used genetically modified mice expressing the enzyme cre recombinase in glutamatergic VGLUT2-positive neurons (CEUA 1143/2022), and injected unilaterally in the pFL region a cre-dependent adeno-associated retrograde virus to express the FLP recombinase, followed by a cre- and FLP-dependent virus to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (hM4D-Gi) only in pFL glutamatergic interneurons. Using whole-body plethysmography, we measured respiratory frequency (fR), tidal volume (VT), pulmonary ventilation (VE), duration of respiratory cycle, inspiration (DI) and expiration (DE) at normocapnia and hypercapnia (7% CO2) after activating the hM4D-Gi in the pFL glutamatergic interneurons with JHU 37160 (0.1 mg/kg; i.p.). Data are expressed as mean ± standard deviation. By analyzing the expression of mCherry fluorescent protein, we found a significant number of glutamatergic interneurons in the pFL region (68.22 ± 11.7; n=18). At normocapnia, JHU injection did not change the ventilatory parameters of VGLUT2(cre/cre + hM4D-Gi) (n=18) and VGLUT2(cre/cre) (n=12) mice [(ΔfR: -2.4±51 vs 0.2±48 cpm; p=0.88) (ΔVT: -1.3±4 vs -0.2±1 μL·g−1; p=0.39) (ΔVE: -39 ±1198 vs -71±607 μL·g−1·min−1; p=0.72) (ΔCycle duration: 5.3±41 vs -1.9±45 ms; p=0.65) (ΔDI: 6.6±14 vs 6±20 ms; p=0.92) (ΔDE: -1.3±35 vs -1.6±31 ms; p=0.97)]. On the other hand, JHU injection attenuated the hypercapnia-induced ventilatory responses of VGLUT2(cre/cre + hM4D-Gi) (n=18) mice when compared to VGLUT2(cre/cre) (n=9) [(ΔfR: 67±69 vs 157±41 cpm; p=0.0003) (ΔVT: 3.8±5 vs 11.9±4 μL·g−1; p&lt;0.0001) (ΔVE: 2052±2197 vs 5374±1773 μL·g−1·min−1; p&lt;0.0001) (Δcycle duration: -46±50 vs -107±49 ms; p=0.002) (ΔDI: -3.7±16 vs -21±19 ms; p=0.011) (ΔDE: -42±41 vs -86±36 ms; p=0.01)]. In conclusion, our data demonstrate that the pFL glutamatergic interneurons are important for the ventilatory response of mice to hypercapnia. FAPESP, CNPq and CAPES. 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.

Inhalation of Aerosolized Fentanyl Induces Respiratory Disorder and Sudden Death in Anesthetized Rats

In synthetic opioids, fentanyl (FNT) is the deadliest in clinical settings, resulting from respiratory disorder (RD) including ventilatory depression (dVE) and apnea. Rapid intravenous injection of FNT has been reported to cause immediately central and upper airway obstructive apnea that is mediated by vagal afferents in anesthetized rat (Zhuang J et al, 2012 and 2023). Here we asked whether acute inhalation of FNT also induced similar RD. EMGs of the internal and external intercostal muscles and thyroarytenoid muscles (EMGII, EMGEI, and EMGTA), minute ventilation (VE), heart rate and arterial blood pressure were recorded in anesthetized rats exposed to aerosolized FNT for 10 min. Immediately after exposure to FNT at 100 mg/m3, the rats showed apneas and remarkable prolongation of expiratory duration (TE) associated with hypotension and bradycardia. The apneas were characterized by cessation of EMGEI activity (central apnea) with enhanced tonic discharges of EMGTA (vocal closure, i.e., obstructive apnea) and EMGII (expiratory muscle constriction, i.e., chest wall rigidity). After a brief rebound at ~0.5 min exposure when the cardiorespiratory activities almost recovered to the baseline level, the rats presented gradual dVE by reduction of VT and fR, lasting for approximately 10 min. Apneas and ventilatory arrest subsequently occurred, leading to cardiac arrest a few minutes later. In contrast, FNT at 50 mg/m3 initially failed to significantly change VE, but subsequently developed gradual dVE (70% reduction) with significant TE prolongation, bradycardia and hypotension. These cardiorespiratory responses disappeared 30 min later. Our results suggest that acute exposure to a lethal dose of aerosolized FNT initially induces both central and upper airway obstructive apnea followed by dVE and ventilatory arrest, which is responsible for the sudden death in anesthetized rats. Supported by NIH R01 grants HL163512 and DA059063. 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.

Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing.

Fentanyl elicits profound disturbances in ventilatory control processes in humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on the frequency of breathing (Freq), tidal volume (TV), and minute ventilation (MV = Freq × TV) are resolved, then depression of breathing is no longer a concern. The results of the present study challenge this concept with findings, as they reveal that while the apparent inhibitory effects of fentanyl (75μg/kg, IV) on Freq, TV, and MV in adult male rats were fully resolved within 15 min, many other fentanyl-induced responses were in full effect, including opposing effects on respiratory timing parameters. For example, although the effects on Freq were resolved at 15 min, inspiratory duration (Ti) and end inspiratory pause (EIP) were elevated, whereas expiratory duration (Te) and end expiratory pause (EEP) were diminished. Since the effects of fentanyl on TV had subsided fully at 15 min, it would be expected that the administration of an opioid receptor (OR) antagonist would have minimal effects if the effects of fentanyl on this and other parameters had resolved. We now report that the intravenous injection of a 1.0mg/kg dose of the peripherally restricted OR antagonist, methyl-naloxone (naloxone methiodide, NLXmi), did not elicit arousal but elicited some relatively minor changes in Freq, TV, MV, Te, and EEP but pronounced changes in Ti and EIP. In contrast, the injection of a 2.5mg/kg dose of NLXmi elicited pronounced arousal and dramatic changes in many variables, including Freq, TV, and MV, which were not associated with increases in non-apneic breathing events such as apneas. The two compelling conclusions from this study are as follows: 1) the blockade of central ORs produced by the 2.5mg/kg dose of NLXmi elicits pronounced increases in Freq, TV, and MV in rats in which the effects of fentanyl had apparently resolved, and 2) it is apparent that fentanyl had induced the activation of two systems with counter-balancing effects on Freq and TV: one being an opioid receptor inhibitory system and the other being a non-OR excitatory system.

Evaluation of Fetal Breathing-Related Nasal Fluid Flow Doppler in the Third Trimester in Pregnant Women with Fetal Growth Restriction: Preliminary Observations.

To investigate the fetal breathing-related nasal fluid flow Doppler waveforms as an indicator of fetal respiratory function in fetuses diagnosed with fetal growth restriction (FGR) in the third trimester. This prospective, non-interventional case-control study was conducted on 96 pregnant women, including 23 pregnant women diagnosed with FGR in the third trimester as the FGR group and 73 healthy pregnant women with fetuses appropriate for gestational age (AGA) as the control group. Fetal breathing-related nasal fluid flow Doppler was examined in the fetuses of the participants. Inspiration and expiration duration, inspiration and expiration peak velocity, total breathing duration, and number of fetal breaths per minute were calculated. Both groups were similar in terms of the duration of inspiration, duration of expiration, and total breathing duration (p=0.463, p=0.711, p=0.520, respectively). Peak inspiratory velocity and peak expiratory velocity were significantly lower in the FGR group than in the control group, and the number of fetal breaths per minute was similar in both groups (p=0.027, p=0.012, p=0.768, respectively). When participants were regrouped into those whose newborn was admitted to the neonatal intensive care unit (NICU) after birth and those who were not, all fetal nasal fluid flow Doppler parameters were similar in both groups. Although the number of participants was too small to draw a definitive conclusion, FGR appears to be associated with a decrease in peak inspiratory and expiratory velocity. The clinical significance of changes in fetal breathing-related nasal fluid flow Doppler parameters in FGR is as yet unclear, and their use in clinical follow-up and predicting unfavorable perinatal outcomes are the subjects of future research.

Different effects of inspiratory duration and expiratory duration on heart rate deceleration capacity and heart rate asymmetry

PurposeLow values of heart rate deceleration capacity (DC) and heart rate asymmetry (HRA) are associated with cardiovascular risks. Slow respiration has been proven to enhance the magnitudes of these indexes, but individual inspiratory (TI) and expiratory (TE) durations were not controlled in most studies. This study aims to examine whether the effects of TI and TE on these indexes would be the same and, if not, how to adjust TI and TE to maximize the effect of slow respiration.MethodsWe evaluated 14 seated healthy young adults who randomly controlled their breathing to nine combinations of TI and TE, each chosen respectively from 2, 4, and 6 s. A 5-min R-R interval time series was obtained from each study period for further analysis.ResultsThe magnitude of DC increased when TI or TE increased, while that of acceleration capacity (AC) remained almost unchanged by TI. We further defined a new index as 100 × DC2/(DC2 + AC2) and found it to be correlated with conventional Guzik’s (r = 0.94) and Porta's (r = 0.99) indexes of HRA during different combinations of TI and TE. Increasing TI and increasing TE both enhanced the magnitudes of HRA indexes, with TI taking effect when ≤ 4 s, and TE taking effect when > 4 s. DC and HRA indexes were maximized with a TI of 4 s and a TE of 6 s.ConclusionWe suggest that a TI of 3–4 s with a TE of 7–6 s is an appropriate standard for slow respiration.

Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation.

Lung volume measurements are important for monitoring functional aeration and recruitment, and may help guide adjustments in ventilator settings. The expiratory phase of APRV may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (TExp). We hypothesized that expiratory flow rate would correlate with estimated lung volume (ELV), as measured using a modified nitrogen washout/washin technique in a large animal lung injury model. Eight pigs (35.2±1.0kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration (TLow), which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15mmHg in normal and Tween-injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC InView Tool. The expiratory flow-time slope and TExp were measured from the expiratory flow profile. Lung elastance increased with Tween-induced lung injury from 29.3±7.3cmH2O/L to 39.9±15.1cmH2O/L and chest wall elastance increased with increasing intra-abdominal pressures from 15.3±4.1cmH2O/L to 25.7±10.0cmH2O/L in the normal lung and 15.8±6.0cmH2O/L to 33.0±6.2cmH2O/L in the Tween-injured lung (p=0.39). ELV decreased from 1.90±0.83L in the Tween-Injured lung to 0.67±0.1L by increasing intra-abdominal pressures to 15mmHg. This had a significant correlation with a TExp decrease from 2.3±0.8s to 1.0±0.1s in the Tween-injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29±0.06L/s2 to 0.63±0.05L/s2 (ρ = 0.78). Changes in ELV over time, and the TExp and flow-time slope, can be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.

Cardiorespiratory patterns of male South American sea lions (Otaria flavescens) resting on land.

The goal of this study was to characterize the cardiorespiratory patterns of male South American sea lions (SASLs, Otaria flavescens) resting on land. We recorded respiratory and heart rate (n = 360 individuals studied) by observing the nostrils, chest movements and the impact of the heart on the thoracic wall. The sea lions breathe apneustically with a pause on inspiration, representing 74% of the respiratory cycle. The mean breathing frequency was 3.2 ± 1.0breathsmin-1, with a breathing cycle presenting periods of bradypneas, tachypneas, and long-term post-inspiratory pauses. The normal heart rate (nHR) was 73.4 ± 14.5beats min-1 and no significant differences were observed between age classes. All animals showed variability in HR in relation to respiratory phases (Inspiration: 101.2 ± 18.4beatsmin-1; post-inspiratory pause: 73.4 ± 14.5beatsmin-1; expiration: 64.6 ± 17.7beatsmin-1), consistent with respiratory sinus arrhythmia (RSA). The mean HR (measured during all respiratory phases) was 79.9 ± 22.7beatsmin-1, and was significantly different between age classes. The total duration of respiratory cycle, and duration of both inspiration and expiration, decreased with an increment in ambient temperature, with no variation in the pause duration. Heart rate during pause and expiration was significantly higher during high temperatures. Similar changes in cardiorespiratory patterns have been reported in other pinnipeds. Our results showed ontogenetic differences in development and typical variations with environmental and behavioral variables.

Efficacy of Marker-Based Motion Capture for Respiratory Cycle Measurement: A Comparison with Spirometry.

Respiratory rate monitoring is fundamental in clinical settings, and the accuracy of measurement methods is critical. This study aimed to develop and validate methods for assessing respiratory rate and the duration leof respiratory cycle phases in different body positions using optoelectronic plethysmography (OEP) based on a motion capture video system. Two analysis methods, the summation method and the triangle method were developed. The study focused on determining the optimal number of markers while achieving accuracy in respiratory parameter measurements. The results showed that most analysis methods showed a difference of ≤0.5 breaths per minute, with R2 ≥ 0.94 (p < 0.001) compared to spirometry. The best OEP methods for respiratory rate were the abdominal triangles and the sum of abdominal markers in all body positions. The study explored inspiratory and expiratory durations. The research found that 5-9 markers were sufficient to accurately determine respiratory time components in all body positions, reducing the marker requirements compared to previous studies. This interchangeability of OEP methods with standard spirometry demonstrates the potential of non-invasive methods for the simultaneous assessment of body segment movements, center of pressure dynamics, and respiratory movements. Future research is required to improve the clinical applicability of these methods.

Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry.

Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS. The immediate goal of mechanical ventilation in ARDS should be to prevent atelectrauma resulting from repetitive alveolar collapse and reopening. However, a long-term goal should be to re-open collapsed and edematous regions of the lung and reduce regions of high mechanical stress that lead to regional volutrauma. In this paper, we consider the proposed strategy used by the full-term newborn to open the fluid-filled lung during the initial breaths of life, by ratcheting tissues opened over a series of initial breaths with brief expirations. The newborn's cry after birth shares key similarities with the Airway Pressure Release Ventilation (APRV) modality, in which the expiratory duration is sufficiently short to minimize end-expiratory derecruitment. Using a simple computational model of the injured lung, we demonstrate that APRV can slowly open even the most recalcitrant alveoli with extended periods of high inspiratory pressure, while reducing alveolar re-collapse with brief expirations. These processes together comprise a ratchet mechanism by which the lung is progressively recruited, similar to the manner in which the newborn lung is aerated during a series of cries, albeit over longer time scales.

Identifi cation of objective indicators of respiratory disorders in primary schoolchildren who stutter

The article presents the results of studying the respiratory function and speech breathing in primary school age children who stutter (CWS) using psychological, pedagogical and instrumental methods to obtain an objective picture of the state of physiological and speech breathing in this category of children. The examination was aimed at studying physiological, phonation, and speech breathing. Electrophysiological examination of the respiratory function included: determination of the type of breathing; registration of vital capacity of the lungs (VC), forced expiratory duration (FVC), forced expiratory volume in the first second (FEV1) using pneumography, spirometry and peak flowmetry. The study results of physiological breathing of CWS showed in half of the children a decrease in the vital volume of air in the lungs, the presence of a mixed type of breathing, in some of them – respiratory rhythm insufficiency. The study results of the maximum phonation time showed that the duration of the phonation exhalation did not correspond to the norm in more than half of the children. A disorder of the formation of speech breathing was revealed. The results of the studied indicators by age and gender are presented. The obtained data are objective evidence of disorders of physiological, phonation, and speech breathing in primary schoolchildren who stutter which requires targeted corrective work to develop the function of breathing and speech breathing in these children.

Predicting sympathovagal balance using parameters of breathing patterns in abdominal breathing

Introduction. Abdominal breathing is utilized as a non-pharmacological treatment method for various stress-related conditions and autonomic dysfunctions. The objective of the study was to determine the predictors in the modulation of sympathovagal balance, as indicated by the ratio of low frequency to high frequency power of heart rate variability, by utilizing the respiratory pattern parameters recorded during the abdominal breathing model. Material and methods. The study involved a group of 101 healthy subjects, where the breathing pattern was recorded using a respiratory induction plethysmograph. Heart activity was estimated through electrocardiography, followed by heart rate variability analysis during both resting and abdominal breathing. Eight parameters of the breathing pattern were recorded in the subjects during resting breathing and abdominal breathing, presumed to be predictors of the ratio of low frequency to high frequency power of heart rate variability. Separate predictive models were created for this ratio for both the resting and abdominal breathing types. Results. The multilinear regression analysis revealed that the primary predictor with the highest predictive power for determining the balance between sympathetic and parasympathetic cardiac influence, as indicated by the low frequency spectral power to high frequency spectral power ratio, in individuals practicing abdominal breathing is Tidal Volume (unstandardized coefficient = 5.007). This was followed by the duration of expiration (coefficient = -3.831) and respiratory minute-volume (coefficient = 4.415), both of which were recorded during resting breathing. In the abdominal breathing model, the most effective predictors were found to be time-related parameters, specifically the frequency of breathing during abdominal breathing (coefficient = -5.953), the duration of the inspiratory phase (coefficient = -4.037), and the duration of the expiration phase (coefficient = -4.194). Conclusions. Abdominal breathing has the potential to normalize sympathovagal balance by adjusting the duration of inspiration or expiration. Further studies should be conducted to investigate the practical application of breathing pattern parameters in restoring the low frequency to high frequency (LF/HF) ratio, particularly in disorders characterized by elevated sympathovagal balance.

Respiratory Pattern Analysis for Different Breathing Types and Recording Sensors in Healthy Subjects.

Accurate monitoring of respiratory activity can lead to early identification and treatment of possible respiratory failure. However, spontaneous breathing can vary considerably. To quantify this variability, this study aimed at comparing the breathing pattern characteristics obtained from several recording sensors during different breathing types. Respiratory activity was recorded with a pneumotachograph and two inductive plethysmographic bands, thoracic and abdominal, in 23 healthy volunteers (age 21.5±1.2 years, 13 females). The subjects were asked to breathe at their natural rate, in successive stages: first freely, then through their nose, nose and mouth, mouth alone, and finally deep and shallow. Both band signals were compared to the pneumotach-derived (gold standard) volume signal. The time series of inspiratory and expiratory duration, total cycle duration and tidal volume were estimated from each of these signals, and also from the sum of the thoracic and abdominal bands. This composite signal showed the highest correlation with the volume signal for almost all subjects, and also had a significantly higher correlation with those obtained from the gold standard volume, compared to either band. In general, breathing parameters increased from basal to nose-mouth breathing, had a minimum in shallow breathing and a maximum in deep breathing. Women exhibited a significantly longer exhalation phase than men during deep breathing, in the combined bands and the gold standard volume. In conclusion, variations in respiratory cycle morphology in different breathing types can be well captured by the simple addition of abdominal and thoracic band signals.Clinical Relevance- Breathing pattern variability can be identified by the combination of abdominal and thoracic bands.

First Stabilize and then Gradually Recruit: A Paradigm Shift in Protective Mechanical Ventilation for Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed "baby lung"); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a "protective lung approach" (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an "open lung approach" (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a "stabilize lung approach" (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4-6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy.