Respiratory Cycle Research Articles

Superfast Lombard response in free-flying, echolocating bats

Acoustic cues are crucial to communication, navigation, and foraging in many animals, which hence face the problem of detecting and discriminating these cues in fluctuating noise levels from natural or anthropogenic sources. Such auditory dynamics are perhaps most extreme for echolocating bats that navigate and hunt prey on the wing in darkness by listening for weak echo returns from their powerful calls in complex, self-generated umwelts.1,2 Due to high absorption of ultrasound in air and fast flight speeds, bats operate with short prey detection ranges and dynamic sensory volumes,3 leading us to hypothesize that bats employ superfast vocal-motor adjustments to rapidly changing sensory scenes. To test this hypothesis, we investigated the onset and offset times and magnitude of the Lombard response in free-flying echolocating greater mouse-eared bats exposed to onsets of intense constant or duty-cycled masking noise during a landing task. We found that the bats invoked a bandwidth-dependent Lombard response of 0.1-0.2 dB per dB increase in noise, with very short delay and relapse times of 20ms in response to onsets and termination of duty-cycled noise. In concert with the absence call time-locking to noise-free periods, these results show that free-flying bats exhibit a superfast, but hard-wired, vocal-motor response to increased noise levels. We posit that this reflex is mediated by simple closed-loop audio-motor feedback circuits that operate independently of wingbeat and respiration cycles to allow for rapid adjustments to the highly dynamic auditory scenes encountered by these small predators.

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia.

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2-80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

Inhibition of somatostatinergic interneurons of the lateral parafacial region reduces the ventilatory response to hypercapnia of mice

The lateral parafacial region (pFL), which contains excitatory and inhibitory neurons and interneurons, generates active expiration in response to hypercapnia. Inhibition of inhibitory somatostatinergic (Sst)-positive neurons in parafacial region increases pulmonary ventilation, while hypercapnia inhibits some of them intrinsically. However, the role of pFL Sst-positive interneurons (with local projections) in regulating pulmonary ventilation during hypercapnia is unclear. We hypothesized that the pFL Sst-positive interneurons control the pulmonary ventilation of mice under normocapnia and hypercapnia, as part of a local neural network. Herein, we evaluated the impact of pFL Sst-positive interneurons inhibition on pulmonary ventilation of non-anesthetized mice during normocapnia and hypercapnia. We used genetically modified mice, expressing the cre recombinase in Sst-positive neurons, and injected unilaterally a cre-dependent adeno-associated (AAV) retrograde virus in the pFL region to express the FLP recombinase, followed by a cre- and FLP-dependent AAV to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (hM4D-Gi) in the pFL Sst-positive interneurons. We used whole-body plethysmography to measure the respiratory frequency (fR), tidal volume (VT), pulmonary ventilation (VE), as well as the duration of the respiratory cycle, inspiration (DI) and expiration (DE) at normocapnia and hypercapnia (7% CO2) after activation of hM4D-Gi in the pFL Sst-positive interneurons using JHU 37160 (JHU; 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 Sst-positive interneurons (73.43 ± 10.52) in the pFL region (n=14). JHU administration did not affect the ventilatory parameters of Sst(cre/cre) (n= 9) and Sst(cre/cre + hM4D-Gi) (n= 14) groups at normocapnia [(Δ fR: 6.5 ± 33.56 vs. -14.86 ± 49.03 cpm; p= 0.42) (Δ VT: 0.87 ± 1.15 vs. -0.97 ± 2.58 μL·g−1; p= 0.19) (Δ VE: 235.8 ± 388.8 vs. -315.9 ± 725.1 μL·g−1·min−1; p= 0.16) (Δ duration of the respiratory cycle: -13 ± 45.11 vs. 12.34 ± 53.07 ms; p= 0.39) (Δ DI: 10.36 ± 11.23 vs. 14.7 ± 16.38 ms; p= 0.62) (Δ DE: -23.36 ± 42.42 vs. -2.41± 53.58 ms; p= 0.48)]. On the other hand, JHU administration attenuated the hypercapnia-induced responses of all ventilatory parameters, such as fR (Δ: 44.57 ± 56.66 vs. 126± 21.28 cpm; p= 0.0002), VT (Δ: 1.32 ± 3.35 vs. 4.16 ± 2.56 μL·g−1; p= 0.04), VE (Δ: 948.7 ± 1407.1 vs. 2183 ± 909.4 μL·g−1·min−1; p= 0.03), duration of the respiratory cycle (Δ: -44.57 ± 46.31 vs. -122.1 ± 30.7 ms; p= 0.0002), DI (Δ: 6.79 ± 16.36 vs. -13.03 ± 10.19 ms; p= 0.003) and DE (Δ: -51.37 ± 37.50 vs. -109.1 ± 32.78 ms; p= 0.001) in the Sst(cre/cre + hM4D-Gi) compared with the Sst(cre/cre) group. Thus, we conclude that the pFL Sst-positive interneurons control the ventilatory parameters of mice during hypercapnia, but not during normocapnia. 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.

Internet of Things-Based Home Respiratory Muscle Training for Patients with Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

Whether Internet of Things (IoT)-based home respiratory muscle training (RMT) benefits patients with comorbid chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aims to evaluate the effectiveness of IoT-based home RMT for patients with COPD. Seventy-eight patients with stable COPD were randomly divided into two groups. The control group received routine health education, while the intervention group received IoT-based home RMT (30 inspiratory muscle training [IMT] and 30 expiratory muscle training [EMT] in different respiratory cycles twice daily for 12 consecutive weeks). Assessments took place pre-intervention and 12 weeks post-intervention, including lung function tests, respiratory muscle strength tests, the mMRC dyspnea scale, CAT questionnaires, the HAMA scale, and 6-month COPD-related readmission after intervention. Seventy-four patients with COPD were analyzed (intervention group = 38, control group = 36), and the mean age and FEV1 of the patients were 68.65 ± 7.40 years, 1.21 ± 0.54 L. Compared to those of the control population, the intervention group exhibited higher FEV1/FVC (48.23 ± 10.97 vs 54.32 ± 10.31, p = 0.016), MIP (41.72 ± 7.70 vs 47.82 ± 10.99, p = 0.008), and MEP (42.94 ± 7.85 vs 50.29 ± 15.74, p = 0.013); lower mMRC (2.00 [2.00-3.00] vs 1.50 [1.00-2.00], p < 0.001), CAT (17.00 [12.00-21.75] vs 11.00 [9.00-13.25], p < 0.001), and HAMA (7.00 [5.00-9.00] vs 2.00 [1.00-3.00], p < 0.001) scores; and a lower incidence rate of 6-month readmission (22% vs 5%, p = 0.033). Compared with no intervention, IoT-based home RMT may be a more beneficial intervention for patients with COPD.

Changes in insertion resistance of acupuncture accompanying respiratory cycle

Changes in insertion resistance of acupuncture accompanying respiratory cycle

On the Regulation of Arterial Blood Pressure by an Intracranial Baroreceptor

Introduction: There is significant evidence for the existence of an intracranial baroreceptor mechanism(s) capable of sensing physiological changes in cerebral blood flow (Marina et al., 2020). However, little is known about the sensitivity of this mechanism to changes in brain perfusion and its interaction with inputs from the peripheral (arterial) baroreceptors. The aim of this study was to characterise the cardiovascular responses to physiological changes in cerebral perfusion induced by experimental manipulations of intracranial pressure (ICP). Methods: The experiments were performed in adult Sprague-Dawley rats (250–300 g), anesthetized with urethane (induction: 1.3 g kg−1, i.p.; maintenance: 10–25 mg kg−1 h−1, i.v.). The femoral artery and vein were cannulated for measurement of arterial blood pressure (ABP) and administration of anaesthetic. The trachea was cannulated, and the animal was mechanically ventilated. The lateral cerebral ventricles were cannulated and connected via saline-filled catheters to a pressure transducer to record ICP and to a “water column” to allow controlled manipulation of ICP. The experiments included the denervation of the arterial baroceptors, stimulation of the aortic depressor nerve and recording of renal sympathetic nerve activity. Results: The resting ICP in rats anesthetized with urethane was 6.2 ± 0.7 mmHg (n=8). Following a small craniotomy that reduced ICP to 0 mmHg, ABP decreased by 11.2 mmHg (n=6) within 30 min. Restoring the integrity of the intracranial space increased ABP to the baseline level. Progressive increases in ABP were observed in response to experimentally-induced increases in ICP by 5, 10, 15 and 20 mmHg, revealing a linear relationship between ICP and systemic arterial pressure within the physiological range of ICP changes. In the absence of inputs from the arterial baroceptors (bilateral sino-aortic denervation and vagotomy) the ABP responses to ICP increases were preserved. Analysis of the ABP and heart rate responses to the electrical stimulation of the aortic depressor nerve suggested baroreflex re-setting at raised ICP. Renal nerve recordings demonstrated increased sympathetic activity at raised ICP (172 ± 34.91 % at 20 mmHg ICP (p=0.003; n=7) with markedly enhanced bursts of activity during the inspiratory phase of the respiratory cycle. Conclusion: These data demonstrate that the intracranial baroceptor mechanism is highly sensitive to changes in cerebral perfusion within the physiological range and suggest that cerebral blood flow is an important determinant of systemic ABP. The data suggest that at raised ICP the baroreflex control of sympathetic vasomotor activity is reset and provides effective control of arterial blood pressure at a higher level required to compensate for reduced brain perfusion. Marina, N., Christie, I.N., Korsak, A., Doronin, M., Brazhe, A., Hosford, P.S., Wells, J.A., Sheikhbahaei, S., Humoud, I., Paton, J.F. and Lythgoe, M.F., 2020. Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow. Nature Communications, 11(1), 131. This PhD Studentship is funded by the British Heart Foundation. 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.

Body Position Dependent Participation of Abdominal and Thoracic Breathing Movements During the Breathing Cycle

Aims: Both abdominal and thoracic breathing movements play important roles in the mechanics of breathing, participating differently in various body positions with abdominal breathing having a greater role. Recent studies showed that an early proning position of awake, non-intubated patients during the COVID-19 pandemic, even during pregnancy (PMID: 32320506, PMID: 33309507, PMID: 34915799) significantly affected the ventilatory parameters and mortality of SARS-CoV-2 patients. Thus, we hypothesized that in different body positions the participation of abdominal (AB) and thoracic breathing (TB) during the complete respiratory cycle (CRC) is different. To test this, we measured the participation of AB and TB to the CRC in different body positions under resting conditions. Methods: In young participants (N=26) age between 18 and 24 (M=21.3±1.6), changes in abdominal and chest circumferences were measured using plethysmography respiratory belts, during inhalation and exhalation in standing (ST), sitting (SI), supine (SU), prone (PR), and all on fours (AF) body positions. Respiratory frequency was also measured. Results: In different positions, the contribution of AB and TB to CRC were significantly different (F(4,100)=4.999, p=0.004, η2p=0.17). AB was significantly higher than TB in all positions (p&lt;0.001). More specifically, AB gradually increased, while TB gradually decreased in the following order: SU(AB/TB) = 74.8±12.9%/25.2%, ST = 69±16%/31%, PR = 66.8±20.2%/33.2%, SI = 65.5±14.8%/34.5%, AF = 61.1±15.1%/38.9%. A significantly higher value was measured in the SU position compared to AF (p&lt;0.001) and SI (p=0.011) positions; PR and ST positions showed intermediate values, which were not significantly different from those yielded by either of the other positions. Respiratory frequency was similar in different body positions. Conclusions: These data show that different body positions significantly affect the participation of abdominal and thoracic breathing during resting condition, underscoring not only the importance of respiratory distress patients positioning during hospitalization, but its usefulness in developing a respiratory training plan for elite athletes to optimize their physical and mental performance in competitive sports. AK: Ministry of Innovation and Technology (MIT) of Hungary-NRDI TKP2020-NKA-17, TKP2021-EGA-37, and National Research, Development, and Innovation Offce (NKFIH) OTKA K 132596 K_19, and Hungarian Academy of Sciences, Post-Covid 2021-34, and HUN-REN-SU: 02068 of Hungary, JT: ÚNKP-22-4-II-SE-4 (JT), TKP2021-EGA-25. 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.

Importance of both Hemidiaphragms in Maintaining Optimal Breathing Mechanics, Respiratory Rate, and Hemoglobin Oxygen Saturation: a Case Study

Background: The mechanical process of breathing consists of the abdominal breathing (AB) driven/generated by the diaphragm, and thoracic breathing (TB) generated by the intercostal muscles. The coordinated movements of the two portions of diaphragm account for 80% of the inspiration, although their exact roles are still investigated. While bilateral diaphragmatic paralysis causes severe shortness of breath, unilateral hemidiaphragm paralysis is asymptomatic at rest, making it challenging to diagnose. Objective: To measure and compare the amplitudes of abdominal and chest movements in different body positions between a healthy individual and an individual with unilateral diaphragmatic paralysis (phrenic nerve injury). Methods: Changes in the circumference of the abdomen and chest were measured during inhalation and exhalation with respiratory plethysmography belts (placed on standardized reproducible positions on the chest, and abdomen) in different body positions: sitting (SI), standing (ST), lying (SU) and prone (PR) in a healthy (H) individual and an individual with unilateral diaphragmatic paralysis. (Ph). Breathing frequency and other parameters were calculated from the measured signals. Furthermore, the blood oxygen saturation (SpO2) was measured with a pulse oximeter. Results: Percent (%) contribution of abdominal breathing H/Ph: SI: 29.6/16.0; ST: 72.8/50.3; SU: 90.6/-53.5; PR: 32.8/1.1. A negative sign shows paradoxical breathing. Respiratory rate (1/min) H/Ph: SI:18.7/19.4; ST: 19.0/15.0; SU: 15.9/37.5; PR: 16.6/35.9. Phase angle of abdominal and thoracic breathing curves (degrees) H/Ph: SI: 4.09/-5.73; ST: -20.82/-9.48; SU: 3.68/184.29; PR: 25.08/-26.51. In case of a negative sign, chest breathing precedes abdominal expansion, and vice versa in the case of a positive sign. A value around 180 degrees indicates paradoxical breathing, seen in Ph, when SpO2 significantly decreased: SI: 93% vs. SU: 82%. Conclusions: In different body positions, the amplitude changes of the abdomen and chest differed substantially during the complete respiratory cycle. Both portions of diaphragm are important because in unilateral phrenic nerve injury, abdominal breathing markedly decreased in most body positions compared to a healthy individual. Furthermore, paradoxical breathing occurred in a supine position, as indicated by a change in the phase angle. The lowest respiratory rate was measured in standing position (15/min), in which the participation of the abdomen/chest ratio was 50.3%, / 49.7%, while the highest value was obtained in supine position (38 breaths/min), which coincided by a decreased hemoglobin oxygen saturation / i.e. oxygen intake. In case of hemidiaphragm paralysis, the diminished mechanical breathing effciency requires a higher respiratory rate to sustain/maintain hemoglobin oxygen saturation. However, this elevated respiratory rate also increases energy consumption, potentially resulting in dyspnea during physical exertion / exercise. Ministry of Innovation and Technology (MIT) of Hungary-NRDI TKP2020-NKA-17, TKP2021-EGA-37, and National Research, Development, and Innovation Offce (NKFIH) OTKA K 132596 K_19, and Hungarian Academy of Sciences, Post-Covid 2021-34, and HUN-REN-SE: 02068 of Hungary. 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 role of electrical impedance tomography in predicting the failure of non-invasive ventilation in patients with COVID-19-associated hypoxemic acute respiratory failure: a prospective observational study

INTRODUCTION: Data on prediction of the failure of non-invasive lung ventilation (NIV) in patients with respiratory failure associated with COVID-19, based on electrical impedance tomography (EIT) patterns are limited. OBJECTIVE: To identify predictors of non-invasive lung ventilation failure in patients with respiratory insufficiency associated with COVID-19, using electrical impedance tomography data. MATERIALS AND METHODS: A monocenter prospective cohort observational study was conducted in patients with moderate-to-severe COVID-19-associated acute respiratory failure, who underwent NIV in the ICU (n = 43). EIT was used to measure the actual ventilation area (SVENT), hyperinflation area (SHYPER), ventilation delay zone (SRVD), and calculate the proportion of ventilated lungs (AVENT), proportion of hyperinflation area (ZHYPER), proportion of RVD area (ZRVD), as well as the duration of hyperinflation during one respiratory cycle (THYPER), and the ratio of hyperinflation time to inhalation time. RESULTS: The study included 43 patients admitted 15 (10–22) days after the onset of COVID-19. Patients with NIV failure (n = 34) had higher ZHYPER values on the first day (19.5 (16.3–30.5) in the NIV success group and 35.2 (25.0–45.0) in the failure group, AUROC 0.80, p = 0.004, Cut-off 39.7, Se 85 %, Sp 89 %) and the last day (20.6 (10.4–28.5) in the success group and 32.7 (26.4–43.3) in the failure group, AUROC 0.92, p = 0.003, Cut-off 32.7, Se 50 %, Sp 100 %), as well as a higher THYPER/TINSP ratio on the last day of NIV (37.5 (31.0–47.9) in the success group and 65.3 (43.7–88.4) in the failure group, AUROC 0.87, p = 0.001, Cut-off 52.7, Se 71 %, Sp 100 %). AVENT, ZRVD, and inhalation time did not show prognostic significance. CONCLUSIONS: EIT can predict the NIV failure in moderate-to-severe ARDS associated with COVID-19, based on the assessment of alveolar overdistention zones. Further research are needed to investigate this theory.

Impact of abdominal compression on heart and stomach motion for stereotactic arrhythmia radioablation.

To evaluate the effectiveness of abdominal compression (AC) as a respiratory motion management method for the heart and stomach during stereotactic arrhythmia radioablation (STAR). 4D computed tomography (4DCT) scans of patients imaged with AC or without AC (free-breathing: FB) were obtained from ventricular-tachycardia (VT) (n=3), lung cancer (n=18), and liver cancer (n=18) patients. Patients treated for VT were imaged both FB and with AC. Lung and liver patients were imaged once with FB or with AC, respectively. The heart, left ventricle (LV), LV components (LVCs), and stomach were contoured on each phase of the 4DCTs. Centre of mass (COM) translations in the left/right (LR), ant/post (AP), and sup/inf (SI) directions were measured for each structure. Minimum distances between LVCs and the stomach over the respiratory cycle were also measured on each 4DCT phase. Mann-Whitney U-tests were performed between AC and FB datasets with a significance of α=0.05. No statistical difference (all p values were>0.05) was found in COM translations between FB and AC patient datasets for all contoured cardiac structures. A reduction in COM translation with AC relative to FB was patient, direction, and structure specific for the three VT patients. A significant decrease in the AP range of motion of the stomach was observed under AC compared to FB. No statistical difference was found between minimum distances to the stomach and LVCs between FB and AC. AC was not a consistent motion management method for STAR, nor does not uniformly affect the separation distance between LVCs and the stomach. If AC is employed in future STAR protocols, the motion of the target volume and its relative distance to the stomach should be compared on two 4DCTs: one while the patient is FB and one under AC.

Wheatstone bridge sensor arrays in foil by robust μ-via technology combining femtosecond-laser drilling and pulsed electrodeposition

Flexible sensor arrays with multilevel circuits typically require complex production cycles leading to high costs and reliability issues. For establishing flexible arrays of strain sensors in Wheatstone bridge configurations structures on different levels within flexible films have to be connected by robust μ-via technology. Usually, dry etching is used to establish via-holes and direct current (DC) electrodeposition is used to fill them with copper. However, dry etching can lead to damages in the underlying electrode or incomplete removal of polymeric material, as inhomogeneities of polymeric foil thicknesses cannot completely be eliminated. This affects the quality of the plating and the reliability of the μ-via connections. It is aggravated by the fact that DC electroplated copper is often weakened by various defects, such as small voids. This article describes a reliable and less complex fabrication process for a Wheatstone bridge sandwich structure consisting of five polymer interlayers separating four metal layers. The femtosecond-laser μ-via drilling proved to be fast, material selective and therefore tolerant to inhomogeneities of polymeric foil thicknesses. Moreover, pulsed current (PC) electrodeposition significantly improved the quality of the copper filling. No voids were found using electron microscopy. Finally, the respiration monitoring sensors produced using this method were subjected to repetitive cycles of bending and relaxation. At a frequency of five cycles per second, reproducible cycles of signal changes were obtained, indicating the usefulness for detecting respiratory cycles of premature infants.

Mean airway pressure as a parameter of lung-protective and heart-protective ventilation

Mean airway pressure (MAP) is the mean pressure generated in the airway during a single breath (inspiration + expiration), and is displayed on most anaesthesia and intensive care ventilators. This parameter, however, is not usually monitored during mechanical ventilation because it is poorly understood and usually only used in research. One of the main determinants of MAP is PEEP. This is because in respiratory cycles with an I:E ratio of 1:2, expiration is twice as long as inspiration. Although MAP can be used as a surrogate for mean alveolar pressure, these parameters differ considerably in some situations. Recently, MAP has been shown to be a useful prognostic factor for respiratory morbidity and mortality in mechanically ventilated patients of various ages. Low MAP has been associated with a lower incidence of 90-day mortality, shorter ICU stay, and shorter mechanical ventilation time. MAP also affects haemodynamics: there is evidence of a causal relationship between high MAP and low perfusion index, both of which are associated with poor prognosis in mechanically ventilated patients. Elevated MAP values have also been associated with high central venous pressure and lactate, which are indicative of ventilator-associated right ventricular failure and tissue hypoperfusion, respectively. MAP, therefore, is an important parameter to measure in clinical practice. The aim of this review has been to identify the determinants of MAP, the pros and cons of using MAP instead of traditional protective ventilation parameters, and the evidence that supports the use of MAP in clinical practice.

Impact of respiratory cycle during mechanical ventilation on beat-to-beat right ventricle stroke volume estimation by pulmonary artery pulse wave analysis.

The same principle behind pulse wave analysis can be applied on the pulmonary artery (PA) pressure waveform to estimate right ventricle stroke volume (RVSV). However, the PA pressure waveform might be influenced by the direct transmission of the intrathoracic pressure changes throughout the respiratory cycle caused by mechanical ventilation (MV), potentially impacting the reliability of PA pulse wave analysis (PAPWA). We assessed a new method that minimizes the direct effect of the MV on continuous PA pressure measurements and enhances the reliability of PAPWA in tracking beat-to-beat RVSV. Continuous PA pressure and flow were simultaneously measured for 2-3min in 5 pigs using a high-fidelity micro-tip catheter and a transonic flow sensor around the PA trunk, both pre and post an experimental ARDS model. RVSV was estimated by PAPWA indexes such as pulse pressure (SVPP), systolic area (SVSystAUC) and standard deviation (SVSD) beat-to-beat from both corrected and non-corrected PA signals. The reference RVSV was derived from the PA flow signal (SVref). The reliability of PAPWA in tracking RVSV on a beat-to-beat basis was enhanced after accounting for the direct impact of intrathoracic pressure changes induced by MV throughout the respiratory cycle. This was evidenced by an increase in the correlation between SVref and RVSV estimated by PAPWA under healthy conditions: rho between SVref and non-corrected SVSD -0.111 (0.342), corrected SVSD 0.876 (0.130), non-corrected SVSystAUC 0.543 (0.141) and corrected SVSystAUC 0.923 (0.050). Following ARDS, correlations were SVref and non-corrected SVSD -0.033 (0.262), corrected SVSD 0.839 (0.077), non-corrected SVSystAUC 0.483 (0.114) and corrected SVSystAUC 0.928 (0.026). Correction also led to reduced limits of agreement between SVref and SVSD and SVSystAUC in the two evaluated conditions. In our experimental model, we confirmed that correcting for mechanical ventilation induced changes during the respiratory cycle improves the performance of PAPWA for beat-to-beat estimation of RVSV compared to uncorrected measurements. This was demonstrated by a better correlation and agreement between the actual SV and the obtained from PAPWA.

From nasal respiration to brain dynamic.

While breathing is a vital, involuntary physiological function, the mode of respiration, particularly nasal breathing, exerts a profound influence on brain activity andcognitive processes. This review synthesizes existing research on the interactions between nasal respiration and the entrainment of oscillations across brain regions involved in cognition. The rhythmic activation of olfactory sensory neurons during nasal respiration is linked to oscillations in widespread brain regions, including the prefrontal cortex, entorhinal cortex, hippocampus, amygdala, and parietal cortex, as well as the piriform cortex. The phase-locking of neural oscillations to the respiratory cycle, through nasal breathing, enhances brain inter-regional communication and is associated with cognitive abilities like memory. Understanding the nasal breathing impact on brain networks offers opportunities to explore novel methods for targeting the olfactory pathway as a means to enhance emotional and cognitive functions.

Advances in triboelectric nanogenerators for self‐powered wearable respiratory monitoring

AbstractTriboelectric nanogenerators (TENGs) have recently gained attention as a compelling platform technology for building wearable bioelectronics. Aside from being self‐powered, TENGs are lightweight, low in cost, rich in material choice, comfortable to wear, and increasingly versatile with advances in sensitivity and efficiency. Due to these features, TENGs have become appealing in biomedical sensing applications, especially for human respiration monitoring. A wealth of information can be collected by breath‐induced electrical signals, which are crucial in the analysis of a patient's respiratory condition and the early detection of harmful respiratory‐linked diseases. TENGs have thus been used to continuously collect important respiratory data, from the breathing patterns, flow rate, and intensity of an individual's respiratory cycle to the chemicals that may be present in their breath. This review paper provides an overview of recent developments in TENG‐based wearable respiratory monitoring as well as future opportunities and challenges for respiratory healthcare.

In-silico CT lung phantom generated from finite-element mesh.

Several lung diseases lead to alterations in regional lung mechanics, including ventilator- and radiation-induced lung injuries. Such alterations can lead to localized underventilation of the affected areas, resulting in the overdistension of the surrounding healthy regions. Thus, there has been growing interest in quantifying the dynamics of the lung parenchyma using regional biomechanical markers. Image registration through dynamic imaging has emerged as a powerful tool to assess lung parenchyma's kinematic and deformation behaviors during respiration. However, the difficulty in validating the image registration estimation of lung deformation, primarily due to the lack of ground-truth deformation data, has limited its use in clinical settings. To address this barrier, we developed a method to convert a finite-element (FE) mesh of the lung into a phantom computed tomography (CT) image, advantageously possessing ground-truth information included in the FE model. The phantom CT images generated from the FE mesh replicated the geometry of the lung and large airways that were included in the FE model. Using spatial frequency response, we investigated the effect of " imaging parameters" such as voxel size (resolution) and proximity threshold values on image quality. A series of high-quality phantom images generated from the FE model simulating the respiratory cycle will allow for the validation and evaluation of image registration-based estimations of lung deformation. In addition, the present method could be used to generate synthetic data needed to train machine-learning models to estimate kinematic biomarkers from medical images that could serve as important diagnostic tools to assess heterogeneous lung injuries.

Presión media de la vía aérea: ¿parámetro integrador de ventilación pulmonar y circulatoria protectoras?

Mean airway pressure (MAP) is the mean pressure generated in the airway during a single breath (inspiration+expiration), and is displayed on most anaesthesia and intensive care ventilators. This parameter, however, is not usually monitored during mechanical ventilation because it is poorly understood and usually only used in research. One of the main determinants of MAP is PEEP. This is because in respiratory cycles with an I:E ratio of 1:2, expiration is twice as long as inspiration. Although MAP can be used as a surrogate for mean alveolar pressure, these parameters differ considerably in some situations. Recently, MAP has been shown to be a useful prognostic factor for respiratory morbidity and mortality in mechanically ventilated patients of various ages. Low MAP has been associated with a lower incidence of 90-day mortality, shorter ICU stay, and shorter mechanical ventilation time. MAP also affects haemodynamics: there is evidence of a causal relationship between high MAP and low perfusion index, both of which are associated with poor prognosis in mechanically ventilated patients. Elevated MAP values have also been associated with high central venous pressure and lactate, which are indicative of ventilator-associated right ventricular failure and tissue hypoperfusion, respectively. MAP, therefore, is an important parameter to measure in clinical practice. The aim of this review has been to identify the determinants of MAP, the pros and cons of using MAP instead of traditional protective ventilation parameters, and the evidence that supports the use of MAP in clinical practice.

Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam

As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal.A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally,in vivodosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated.The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these filmsin vivoto validate the targeting.The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation andin vivodosimetry.

MousePZT: A simple, reliable, low-cost device for vital sign monitoring and respiratory gating in mice under anesthesia.

Small animal studies in biomedical research often require anesthesia to reduce pain or stress experienced by research animals and to minimize motion artifact during imaging or other measurements. Anesthetized animals must be closely monitored for the safety of the animals and to prevent unintended effects of altered physiology on experimental outcomes. Many currently available monitoring devices are expensive, invasive, or interfere with experimental design. Here, we present MousePZT, a low-cost device based on a simple piezoelectric sensor, with a custom circuit and computer software that allows for measurements of both respiratory rate and heart rate in a non-invasive, minimal contact manner. We find the accuracy of the MousePZT device in measuring respiratory and heart rate matches those of commercial systems. Using the widely-used gas isoflurane and injectable ketamine/xylazine combination, we also demonstrate that changes in respiratory rate are more easily detected and can precede changes in heart rate associated with variations in anesthetic depth. Additional circuitry on the device outputs a respiration-locked trigger signal for respiratory-gating of imaging or other data acquisition and has high sensitivity and specificity for detecting respiratory cycles. We provide detailed instruction documents and all necessary microcontroller and computer software, enabling straightforward construction and utilization of this device.