Diaphragmatic Activity Research Articles

Feasibility of transesophageal phrenic nerve stimulation

BackgroundEvery year, more than 2.5 million critically ill patients in the ICU are dependent on mechanical ventilation. The positive pressure in the lungs generated by the ventilator keeps the diaphragm passive, which can lead to a loss of myofibers within a short time. To prevent ventilator-induced diaphragmatic dysfunction (VIDD), phrenic nerve stimulation may be used.ObjectiveThe goal of this study is to show the feasibility of transesophageal phrenic nerve stimulation (TEPNS). We hypothesize that selective phrenic nerve stimulation can efficiently activate the diaphragm with reduced co-stimulations.MethodsAn in vitro study in saline solution combined with anatomical findings was performed to investigate relevant stimulation parameters such as inter-electrode spacing, range to target site, or omnidirectional vs. sectioned electrodes. Subsequently, dedicated esophageal electrodes were inserted into a pig and single stimulation pulses were delivered simultaneously with mechanical ventilation. Various stimulation sites and response parameters such as transdiaphragmatic pressure or airway flow were analyzed to establish an appropriate stimulation setting.ResultsPhrenic nerve stimulation with esophageal electrodes has been demonstrated. With a current amplitude of 40 mA, similar response figures of the diaphragm activation as compared to conventional stimulation with needle electrodes at 10mA were observed. Directed electrodes best aligned with the phrenic nerve resulted in up to 16.9 % higher amplitude at the target site in vitro and up to 6 cmH20 higher transdiaphragmatic pressure in vivo as compared to omnidirectional electrodes. The activation efficiency was more sensitive to the stimulation level inside the esophagus than to the inter-electrode spacing. Most effective and selective stimulation was achieved at the level of rib 1 using sectioned electrodes 40 mm apart.ConclusionDirected transesophageal phrenic nerve stimulation with single stimuli enabled diaphragm activation. In the future, this method might keep the diaphragm active during, and even support, artificial ventilation. Meanwhile, dedicated sectioned electrodes could be integrated into gastric feeding tubes.

Influence of mild pulmonary congestion on diaphragmatic mobility and activities of daily living in chronic kidney disease: An experimental and clinical study

BackgroundPulmonary congestion is a strong predictor of mortality and cardiovascular events in chronic kidney disease (CKD); however, the effects of the mild form on functionality have not yet been investigated. The objective of this study was to assess the influence of mild pulmonary congestion on diaphragmatic mobility (DM) and activities of daily living (ADL) in hemodialysis (HD) subjects, as well as compare ADL behavior on dialysis and non-dialysis days. In parallel, experimentally induce CKD in mice and analyze the resulting pulmonary and functional repercussions. MethodsThirty subjects in HD underwent thoracic and abdominal ultrasonography, anthropometric assessment, lung and kidney function, respiratory muscle strength assessment and symptoms analysis. To measure ADL a triaxial accelerometer was used over seven consecutive days. Twenty male mice were randomized in Control and CKD group. Thoracic ultrasonography, TNF-α analysis in kidney and lung tissue, exploratory behavior and functionality assessments were performed. ResultsMild pulmonary congestion caused a 26.1% decline in DM (R2=.261; P=.004) and 20% reduction in walking time (R2=.200; P=.01), indicating decreases of 2.23mm and 1.54min, respectively, for every unit increase in lung comet-tails. Regarding ADL, subjects exhibited statistically significant differences for standing (P=.002), walking (P=.034) and active time (P=.002), and number of steps taken (P=.01) on days with and without HD. In the experimental model, CKD resulted in increased levels of TNF-α on kidneys (P=.037) and lungs (P=.02), attenuation of exploratory behavior (P=.01) and significant decrease in traveled distance (P=.034). Thoracic ultrasonography of CKD mice showed presence of B-lines. ConclusionThe mild pulmonary congestion reduced DM and walking time in subjects undergoing HD. Individuals were less active on dialysis days. Furthermore, the experimental model implies that the presence of pulmonary congestion and inflammation may play a decisive role in the low physical and exploratory performance of CKD mice.

A Multichannel EMG System for Spatial Measurement of Diaphragm Activities

An important aspect of mechanical ventilation is the recognition and quantification of spontaneous respiratory effort. However, a measurement of flows and pressures often used for this purpose is prone to error. A promising alternative is to detect diaphragmatic contractions, directly. A method recently proposed is to acquire the diaphragm electromyography (EMG) signals using surface electrodes. However, this method is often limited by disturbances and electrode placements for some applications in which the patient is moving, such as rehabilitation or breathing training. In this work, we present a novel noninvasive method that addresses these problems. This method is based on a novel dry electrode belt, which can be used to comfortably derive EMG signals from the thorax, in combination with a developed electrical measurement system. The modular multichannel system is capable of simultaneously deriving and digitizing 32 differential EMG channels and sending them to a personal computer (PC). A specific digital signal processing chain allows combining the data into one robust overall signal. In addition, the signals derived from the thorax can be used to obtain information regarding the spatiotemporal propagation of the diaphragm EMG. To verify the functionality, the system is characterized. Subsequently, subject measurements are performed. From these, the spatiotemporal propagation of diaphragm EMG on the thorax can be identified. For better visualization, this propagation is graphically displayed in a 3-D model. In addition, it is shown how the combination of all signals can be used to obtain a robust overall signal that can be used to control ventilators.

The effect of proportional assist ventilation on the electrical activity of the human diaphragm during exercise.

What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P<0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P=0.151) but was significantly lower during medium (25%, P=0.02) and high (36%, P<0.001) levels of PAV. The pressure-time product of the diaphragm (PTPdi ) was lower across PAV unloading conditions (P<0.05). The EMGdi was significantly lower in medium and high PAV conditions (P=0.035 and P<0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r=0.61, P=0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease.

Targeting drug or gene delivery to the phrenic motoneuron pool.

Phrenic motoneurons (PhrMNs) innervate diaphragm myofibers. Located in the ventral gray matter (lamina IX), PhrMNs form a column extending from approximately the third to sixth cervical spinal segment. Phrenic motor output and diaphragm activation are impaired in many neuromuscular diseases, and targeted delivery of drugs and/or genetic material to PhrMNs may have therapeutic application. Studies of phrenic motor control and/or neuroplasticity mechanisms also typically require targeting of PhrMNs with drugs, viral vectors, or tracers. The location of the phrenic motoneuron pool, however, poses a challenge. Selective PhrMN targeting is possible with molecules that move retrogradely upon uptake into phrenic axons subsequent to diaphragm or phrenic nerve delivery. However, nonspecific approaches that use intrathecal or intravenous delivery have considerably advanced the understanding of PhrMN control. New opportunities for targeted PhrMN gene expression may be possible with intersectional genetic methods. This article provides an overview of methods for targeting the phrenic motoneuron pool for studies of PhrMNs in health and disease.

OR26-4 Glucocorticoid Receptor Expression and Signaling During Critical Illness, in Relation to the Duration of Illness and the Systemic Glucocorticoid Availability: A Prospective, Observational, Cross-Sectional Human and a Translational Mouse Study

Abstract Critically ill patients are thought to develop maladaptive glucocorticoid-resistance which convinces many clinicians to administer stress doses of glucocorticoids to overcome this state of glucocorticoid-resistance. However, supportive data arises mainly from whole blood cells. It is currently not known if the observed changes in regulators and markers of glucocorticoid signaling and activity are also present in other cell and tissue types with a role in critical illness. We quantified regulators and markers of glucocorticoid signaling and activity in several cell and tissue types in critically ill humans and animals and in healthy controls. We found that throughout critical illness, glucocorticoid activity appeared suppressed in neutrophils, but upregulated in monocytes and skeletal muscle. Also in vital tissues GRα-signaling was altered in a tissue-specific, largely time-independent manner. Increasing systemic glucocorticoid availability increased glucocorticoid activity in adipose tissue, diaphragm and lung, whereas in immune cells and other tissues regulatory pathways counteracted. These data argue against glucocorticoid-treatable generalized glucocorticoid resistance and rather point towards an adaptive response in each specific cell or tissue type to optimally guide the beneficial actions of glucocorticoids to the tissues that need it while protecting collateral undesirable effects in tissue that are harmed by elevated systemic glucocorticoid availability. Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.

Abdominal and Pelvic Floor Activity Related to Respiratory Diaphragmatic Activity in Subjects with and without Non-Specific Low Back Pain.

One of the advances in physiotherapy in recent years is the exploration and treatment by ultrasound imaging. This technique makes it possible to study the relationship between the musculature of the anterolateral wall of the abdomino-pelvic cavity, the pelvic floor muscles and the diaphragm muscle, among others, and thus understand their implication in non-specific low back pain (LBP) in pathological subjects regarding healthy subjects. Objective: To evaluate by RUSI (rehabilitative ultrasound imaging) the muscular thickness at rest of the abdominal wall, the excursion of the pelvic floor and the respiratory diaphragm, as well as to study their activity. Methodology: Two groups of 46 subjects each were established. The variables studied were: non-specific low back pain, thickness and excursion after tidal and forced breathing, pelvic floor (PF) excursion in a contraction and thickness of the external oblique (EO), internal oblique (IO) and transverse (TA) at rest. Design: Cross-sectional observational study. Results: Good-to-excellent reliability for measurements of diaphragm thickness at both tidal volume (TV) (inspiration: 0.763, expiration: 0.788) and expiration at forced volume (FV) (0.763), and good reliability for inspiration at FV (0.631). A correlation was found between the EO muscle and PF musculature with respect to diaphragmatic thickness at TV, inspiration and expiration, and inspiration at FV, in addition to finding significant differences in all these variables in subjects with LBP. Conclusion: Subjects with LBP have less thickness at rest in the OE muscle, less excursion of the pelvic diaphragm, less diaphragmatic thickness at TV, in inspiration and expiration, and in inspiration to FV.

Diaphragm electrical activity during weaning of nasal high-flow therapy in preterm infants

ObjectiveTo determine whether electrical activity of the diaphragm (Edi) changes with weaning nasal high-flow (HF) therapy in preterm infants according to a standardised protocol.DesignProspective observational cohort study.SettingNeonatal intensive care unit.PatientsPreterm...

Quantitative evaluation of diaphragmatic motion during forced breathing in chronic obstructive pulmonary disease patients using dynamic chest radiography.

ObjectiveTo quantitatively evaluate the bilateral diaphragmatic motion difference during forced breathing between chronic obstructive pulmonary disease (COPD) patients and healthy individuals using dynamic chest radiography technique.MethodsThis prospective study included the COPD patients (n: 96, f/m: 17/79, age: 66 ± 8 years old) and healthy individuals (n: 50, f/m: 42/8, age: 53 ± 5 years old) that underwent dynamic chest radiography with a flat panel X-ray detector system during forced breathing in a standing position. After analyzing the excursions, duration and velocity of diaphragmatic motion were automatically calculated using the postprocessing software. The parameters of diaphragmatic motion including excursion, duration, velocity, inhalation/exhalation times were assessed in all subjects for both diaphragms. The correlation between lung function parameters and diaphragmatic motion excursions were further evaluated.ResultsThe excursions of diaphragmatic motion in COPD patients were significantly decreased in COPD patients compared with healthy individuals during forced breathing (P < 0.05). The excursion in COPD patients was 35.93 ± 13.07 mm vs. 41.49 ± 12.07 mm in healthy individuals in the left diaphragm, and 32.05 ± 12.29 mm in COPD patients vs. 36.88 ± 10.96 mm in healthy individuals in the right diaphragm. The duration of diaphragmatic motion significantly decreased in COPD patients, compared with the healthy individuals (P < 0.05). The inhalation time in COPD patients was 2.03 ± 1.19 s vs. 2.53 ± 0.83 s in healthy individuals in the left diaphragm and 1.94 ± 1.32 s in COPD patients vs. 2.23 ± 1.21 s in healthy individuals in the right diaphragm. The exhalation time was 4.77 ± 1.32 s in COPD patients vs. 6.40 ± 2.73 s in healthy individuals in the left diaphragm and 4.94 ± 3.30 s in COPD patients vs. 6.72 ± 2.58 s in healthy individuals in the right diaphragm. The peak velocity of diaphragmatic motion showed no significant difference between COPD and healthy groups. The excursions of bilateral diaphragmatic motion showed moderate correlation with FEV1/FVC (r = 0.44, P < 0.001). Multi-linear regression analysis showed that the excursions of bilateral diaphragm are significantly associated with COPD occurrence (P < 0.05).ConclusionThe excursions and duration of diaphragmatic motion during forced breathing are significantly decreased in COPD patients, compared with healthy individuals. Our study showed that precise bilateral diaphragmatic motion activity can be evaluated by dynamic chest radiography.

Assessment of diaphragmatic mobility by chest ultrasound and basic echocardiography in patients with malignant pleural effusion undergoing pleurodesis

Background Malignant pleural effusion (MPE) is prevalent, and in cases such as aging patients as well as increased long-term survival for metastatic cancers, the number of patients will continue to elevate in the near future. Aim To assess both the diaphragmatic mobility using chest ultrasound and basic echocardiography before and after pleurodesis in patients with MPE. Patients and methods This study included 35 patients with MPE; the diagnosis is based on positive pleural fluid cytology, thoracoscopic biopsy, and fitted for chemical pleurodesis by bleomycin. Baseline chest ultrasound was done to for assess the diaphragmatic mobility and basic echocardiography. Chemical pleurodesis was done through intrapleural injection of 1 IU/kg bleomycin as a sclerosing agent in 100 ml of normal saline. Results Regarding outcome, 17 (48.6%) patients succeeded (defined as absent lung sliding and no reaccumulation of pleural fluid in the lines examined) and 7 (20%) patients failed (known as reaccumulation of pleural fluid and (even with) no presence of lung sliding). There was a statistically substantial decrease in the diaphragmatic excursion (mobility) at 2 weeks and at 2 months after pleurodesis than before. A significant relation was detected between outcome of the studied patients with lung sliding before pleurodesis, whereas there was a substantial increase in pleurodesis success with no presence of lung sliding at 2 weeks and at 2 months after pleurodesis. Conclusion Ultrasound of the diaphragm is an uncomplicated, noninvasive method for estimating the contractile activity of diaphragm. The decrease in the diaphragmatic excursion at 2 weeks and at 2 months after pleurodesis compared with that before pleurodesis can be used as sign to predict pleurodesis success. There is no significant relation between echocardiography measurements and outcome except that normal left ventricle ejection fraction % has a significant relation with increased success outcome.

Visible abdominal distension in functional gut disorders: Objective evaluation.

Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation). A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n= 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35. (A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent). In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity.

Liposomal Bupivacaine’s Effect on the Diaphragm: Comment

We read with great interest the article by Berg et al.1 about the evaluation of diaphragmatic excursion after interscalene nerve block with liposomal bupivacaine versus plain bupivacaine.In their study, the authors investigated as a primary outcome the effect of liposomal bupivacaine combined with plain bupivacaine versus plain bupivacaine alone on diaphragmatic excursion during sigh (deep) and sniff (shallow) breathing in patients undergoing total shoulder arthroscopy in the immediate postoperative period and after 24 h.1The study did not detect a difference between the two groups in absolute values of diaphragm excursion during a sigh breath at 24 h (P = 0.112), despite a greater than 1 cm difference observed. In addition, a significant difference between groups was noted in the percentage change with respect to preblock levels: –24% in the liposomal bupivacaine with bupivacaine group compared with +9% in the bupivacaine group.The authors concluded that the addition of liposomal bupivacaine to bupivacaine, in an interscalene block, results in statistically significant reductions in diaphragm excursion and pulmonary function testing 24 h after block placement compared with bupivacaine alone. The accompanying editorial underlined the need for caution in the use of liposomal bupivacaine for interscalene nerve block in patients with any pulmonary compromise.2We have two comments on this study. First, we observed that the two groups were already rather different in their baseline values, as reported in their table 2. This was particularly true for the diaphragmatic excursion (higher in the liposomal bupivacaine with bupivacaine group), the percent change of which at 24 h was the primary outcome of the study.1 The authors did not discuss this issue, but, indeed, this baseline difference might have influenced the finding of a larger percent change in diaphragmatic excursion at 24 h compared with baseline.1Second, the authors used the percentage change in diaphragmatic excursion as a measure of the level of diaphragmatic paralysis, as defined by Renes et al.,3 who proposed that a 0 to 25% reduction from baseline could be considered as no paralysis, 25 to 75% reduced could be considered as partial paralysis, and a greater than 75% reduction could be considered as complete paralysis. However, as recently reported in this journal, 24 h after interscalene nerve block, the level of diaphragmatic paralysis measured with diaphragmatic excursion may be compensated by parasternal muscle activity.4 Therefore, we believe that changes in diaphragmatic excursion alone cannot be considered as an adequate measure of diaphragmatic function.For this reason, we propose that diaphragmatic thickening fraction can be a more appropriate tool for investigating the action of medications on the diaphragm. The thickening fraction is calculated as the maximal diaphragm thickness (assessed using linear probe) during inspiration (Tdi, pi) minus the diaphragm thickness at end-expiration (Tdi, ee) divided by the Tdi, ee and multiplied by 100.5 Compared with diaphragmatic excursion, thickening fraction is a more sensitive and qualitatively accurate parameter and provides a more comprehensive measure of diaphragm contraction.Excursion of the left hemidiaphragm is more difficult to assess than the right one and this is due to interference from gastric contents and the less favorable spleen’s window. Berg et al.1 performed 13 left blocks, but they did not comment on difficulties experienced in the evaluation of the excursion of the left hemidiaphragm. In any case, use of the thickening fraction to measure and evaluate diaphragm activity would overcome this problem and should be used in the research field.Of course, we understand that standard perioperative ultrasound practice does not normally include calculating the thickening fraction, being a more difficult measure to obtain and is mostly used to assess weaning from mechanical ventilation in the intensive care unit.5 As a matter of fact, there is a bit of a schism between point-of-care ultrasound use in the operating room and intensive care settings. However, the skills required to measure thickening fraction are relatively easy to acquire under expert supervision.6In conclusion, considering the aforementioned limitations, we suggest caution in assessing the risk of adverse events in terms of diaphragmatic and pulmonary function, including dyspnea and oxygen need, with the use diaphragmatic excursion only.Dr. Cammarota declares a financial relationship with Getinge MSD (Växjö, Sweden). The other authors declare no competing interests.

AMPK-Nrf2 Signaling Pathway in Phrenic Motoneurons following Cervical Spinal Cord Injury

High spinal cord injuries (SCI) induce the deafferentation of phrenic motoneurons, leading to permanent diaphragm paralysis. This involves secondary injury associated with pathologic and inflammatory processes at the site of injury, and at the level of phrenic motoneurons. In the present study, we evaluated the antioxidant response in phrenic motoneurons involving the AMPK-Nrf2 signaling pathway following C2 spinal cord lateral hemi-section in rats. We showed that there is an abrupt reduction in the expression of phosphorylated AMPK and Nrf2 at one hour post-injury in phrenic motoneurons. A rebound is then observed at one day post-injury, reflecting a return to homeostasis condition. In the total spinal cord around phrenic motoneurons, the increase in phosphorylated AMPK and Nrf2 occurred at three days post-injury, showing the differential antioxidant response between phrenic motoneurons and other cell types. Taken together, our results display the implication of the AMPK-Nrf2 signaling pathway in phrenic motoneurons’ response to oxidative stress following high SCI. Harnessing this AMPK-Nrf2 signaling pathway could improve the antioxidant response and help in spinal rewiring to these deafferented phrenic motoneurons to improve diaphragm activity in patients suffering high SCI.

Simultaneous measurement of diaphragm activity, chest impedance, and ECG using three standard cardiorespiratory monitoring electrodes.

Current cardiorespiratory monitoring in neonates with electrocardiogram (ECG) and chest impedance (CI) has limitations. Adding transcutaneous electromyography of the diaphragm (dEMG) may improve respiratory monitoring, but requires additional hardware. We aimed to determine the feasibility of measuring dEMG and ECG/CI simultaneously using the standard ECG/CI hardware, with its three electrodes repositioned to dEMG electrode locations. Thirty infants (median postmenstrual age 30.4 weeks) were included. First, we assessed the feasibility of extracting dEMG from the ECG-signal. If successful, the agreement between dEMG-based respiratory rate (RR), using three different ECG-leads, and a respiratory reference signal was assessed using the Bland-Altman analysis and the intraclass correlation coefficient (ICC). Furthermore, we studied the agreement between CI-based RR and the reference signal with the electrodes placed at the standard and dEMG position. Finally, we explored the quality of the ECG-signal at the different electrode positions. In 15 infants, feasibility of measuring dEMG with the monitoring electrodes was confirmed. In the next 15 infants, comparing dEMG-based RR to the reference signal resulted in a mean difference and limits of agreement for ECG-lead I, II and III of 4.2 [-8.2 to 16.6], 4.3 [-10.7 to 19.3] and 5.0 [-14.2 to 24.2] breaths/min, respectively. ICC analysis showed a moderate agreement for all ECG-leads. CI-based RR agreement was similar at the standard and dEMG electrode position. An exploratory analysis suggested similar quality of the ECG-signal at both electrode positions. Measuring dEMG using the ECG/CI hardware with its electrodes on the diaphragm is feasible, leaving ECG/CI monitoring unaffected.

Diaphragm Electromyography Versus Ultrasonography in the Prediction of Mechanical Ventilation Liberation Outcome.

ICU-acquired diaphragm paresis occurs in about 25% of patients after prolonged mechanical ventilation. Diaphragm function can be evaluated via several approaches including monitoring of electrical activity of diaphragm (electromyography [EMG]) or ultrasound (US) measurements. We aimed to assess the usefulness of diaphragm EMG indices in predicting liberation outcome in comparison with diaphragm US measurements. We included consecutive subjects invasively ventilated for > 48 h for acute respiratory failure and who were considered ready to undergo a spontaneous breathing trial (SBT). Exclusion criteria were age < 18 y, pregnancy, tracheostomy, or patients with confirmed neuromuscular diseases. To start the SBT, we set pressure support to 0 cm H2O and PEEP to 5 cm H2O. During the initial 5 min of SBT, mean values of Δ electrical activity of the diaphragm (ΔEAdi) (EAdi peak - EAdi minimal), tidal volume (VT), and breathing frequency were measured. Neuroventilatory efficiency was calculated as VT divided by ΔEAdi. Rapid shallow breathing index was calculated as breathing frequency divided by VT. US examination of the diaphragm and assessment of diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) were recorded 30 min after initiation of SBT. Twenty-four subjects were included; DTF predicted weaning failure with area under the curve 0.96 and P value < .001 with sensitivity 100% and specificity 94% for the cutoff value ≤ 15%. DE for the cutoff ≤ 1.56 cm showed sensitivity 75% and specificity 69%, whereas ΔEAdi with cutoff value ≤ 4 μV showed sensitivity 25% and specificity 100%. Neuroventilatory efficiency with cutoff value ≤ 29 mL/μV showed sensitivity 50% and specificity 81%. All 3 parameters showed nonsignificant results with area under the curve 0.73, 0.56, and 0.62 and P values .08, .65, and .34, respectively. Diaphragm EMG indices were inferior to diaphragm ultrasonography in prediction of mechanical ventilation liberation outcome.

Laryngeal and swallow dysregulation following acute cervical spinal cord injury.

Laryngeal function is vital to airway protection. Although swallow is mediated by the brainstem, the mechanism underlying the increased risk of dysphagia after cervical spinal cord injury (SCI) is unknown. We hypothesized that: 1) loss of descending phrenic drive affects swallow and breathing differently, and 2) loss of ascending spinal afferent information alters swallow regulation. We recorded electromyograms (EMGs) from upper airway and chest wall muscles in freely breathing pentobarbital-anesthetized cats and rats. Laryngeal abductor activity during inspiration increased about twofold following C2 lateral hemisection. Ipsilateral to the injury, the crural diaphragm EMG amplitude was reduced during breathing (62 ± 25% change postinjury), but no animal had complete termination of activity; 75% of animals had increased contralateral diaphragm recruitment, but this did not reach significance. During swallow, laryngeal adductor and pharyngeal constrictor muscles increased activity, and diaphragm activity was bilaterally suppressed. This was unexpected because of the ipsilateral-specific response during breathing. Swallow-breathing coordination was disrupted by injury, and more swallows occurred during early expiration. Finally, to determine if the chest wall is a major source of feedback for laryngeal regulation, we performed T1 total transections in rats. As in the C2 lateral hemisection, inspiratory laryngeal recruitment was the first feature noted after injury. In contrast to the C2 lateral hemisection, diaphragmatic drive increased after T1 transection. Overall, we found that SCI alters laryngeal drive during swallow and breathing, and alters swallow-related diaphragm activity. Our results show behavior-specific effects, suggesting that swallow is affected more than breathing is by SCI, and emphasizing the need for additional studies on the effect of ascending afferents from the spinal cord on laryngeal function.NEW & NOTEWORTHY This is the first manuscript to determine the impact of cSCI on laryngeal and swallow function, and to describe a possible mechanism for dysphagia and altered airway protection after injury.

Identification of the Tidal Volume Response to Pulse Amplitudes of Phrenic Nerve Stimulation Using Gaussian Process Regression.

While mechanical ventilation (MV) can lead to ventilator-induced diaphragmatic atrophy due to diaphragm inactivity, electrical phrenic nerve stimulation (PNS) can keep the diaphragm active and therefore prevent diaphragmatic weakness. To quantify the effectivity of PNS, an identification experiment during PNS is presented, and its data is used in Gaussian process regression (GPR) of the tidal volume based on the constant voltage amplitude of the stimulation pulses. The measurements were split into training data of variable size and test data for cross validation. For variable training sizes and different PNS settings, the GPR had a root mean square deviation (RMSD) between 0.39 and 0.91 mL/kg. An identification experiment as short as one and a half minutes was able to characteristically capture the relationship between tidal volume and voltage amplitude. The proposed method needs to be validated in further experiments.

Mitochondrial adaptations to inactivity in diaphragm muscle fibers.

Type I and IIa diaphragm muscle (DIAm) fibers comprise slow and fast fatigue-resistant motor units that are recruited to accomplish breathing and thus have a high duty cycle. In contrast, type IIx/IIb fibers comprise more fatigable fast motor units that are infrequently recruited for airway protective and straining behaviors. We hypothesize that mitochondrial structure and function in type I and IIa DIAm fibers adapt in response to inactivity imposed by spinal cord hemisection at C2 (C2SH). At 14 days after C2SH, the effect of inactivity on mitochondrial structure and function was assessed in DIAm fibers. Mitochondria in DIAm fibers were labeled using MitoTracker Green (Thermo Fisher Scientific), imaged in three-dimensions (3-D) by fluorescence confocal microscopy, and images were analyzed for mitochondrial volume density (MVD) and complexity. DIAm homogenate from either side was assessed for PGC1α, Parkin, MFN2, and DRP1 using Western blot. In alternate serial sections of the same DIAm fibers, the maximum velocity of the succinate dehydrogenase reaction (SDHmax) was determined using a quantitative histochemical technique. In all groups and both sides of the DIAm, type I and IIa DIAm fibers exhibited higher MVD, with more filamentous mitochondria and had higher SDHmax normalized to both fiber volume and mitochondrial volume compared with type IIx/IIb Diam fibers. In the inactive right side of the DIAm, mitochondria became fragmented and MVD decreased in all fiber types compared with the intact side and sham controls, consistent with the observed reduction in PGC1α and increased Parkin and DRP1 expression. In the inactive side of the DIAm, the reduction in SDHmax was found only for type I and IIa fibers. These results show that there are intrinsic fiber-type-dependent differences in the structure and function of mitochondria in DIAm fibers. Following C2SH-induced inactivity, mitochondrial structure (MVD and fragmentation) and function (SDHmax) were altered, indicating that inactivity influences all DIAm fiber types, but inactivity disproportionately affected SDHmax in the more intrinsically active type I and IIa fibers.NEW & NOTEWORTHY Two weeks of diaphragm (DIAm) inactivity imposed by C2SH caused reduced mitochondrial volume density, mitochondrial fragmentation, and a concomitant reduction of SDHmax in type I and IIa DIAm fibers on the lesioned side. Type I and IIa DIAm fibers were far more sensitive to inactivation than type IIx/IIb fibers, which exhibited little pathology. Our results indicate that mitochondria in DIAm fibers are plastic in response to varying levels of activity.

Effects of C2 hemisection on respiratory and cardiovascular functions in rats.

High cervical spinal cord injuries induce permanent neuromotor and autonomic deficits. These injuries impact both central respiratory and cardiovascular functions through modulation of the sympathetic nervous system. So far, cardiovascular studies have focused on models of complete contusion or transection at the lower cervical and thoracic levels and diaphragm activity evaluations using invasive methods. The present study aimed to evaluate the impact of C2 hemisection on different parameters representing vital functions (i.e., respiratory function, cardiovascular, and renal filtration parameters) at the moment of injury and 7 days post-injury in rats. No ventilatory parameters evaluated by plethysmography were impacted during quiet breathing after 7 days post-injury, whereas permanent diaphragm hemiplegia was observed by ultrasound and confirmed by diaphragmatic electromyography in anesthetized rats. Interestingly, the mean arterial pressure was reduced immediately after C2 hemisection, with complete compensation at 7 days post-injury. Renal filtration was unaffected at 7 days post-injury; however, remnant systolic dysfunction characterized by a reduced left ventricular ejection fraction persisted at 7 days post-injury. Taken together, these results demonstrated that following C2 hemisection, diaphragm activity and systolic function are impacted up to 7 days post-injury, whereas the respiratory and cardiovascular systems display vast adaptation to maintain ventilatory parameters and blood pressure homeostasis, with the latter likely sustained by the remaining descending sympathetic inputs spared by the initial injury. A better broad characterization of the physiopathology of high cervical spinal cord injuries covering a longer time period post-injury could be beneficial for understanding evaluations of putative therapeutics to further increase cardiorespiratory recovery.

Multicentre paired non-inferiority study of the cardiorespiratory monitoring performance of the wireless and non-adhesive Bambi® belt measuring diaphragm activity in neonates: study protocol

IntroductionCardiorespiratory monitoring is used in the neonatal intensive care unit (NICU) to assess the clinical status of newborn infants and detect critical deteriorations in cardiorespiratory function. Currently, heart rate (HR)...