Measurement Of Transdiaphragmatic Pressure Research Articles

No effect of aerobic fitness on exercise-induced diaphragm fatigue in females.

We tested the hypothesis that the incidence and magnitude of diaphragm fatigue following high-intensity exercise would be lower in females with a high aerobic capacity (Hi-Fit) compared with healthy females with an average aerobic fitness (Avg-Fit). Participants were assigned to groups based on their peak O2 uptake (V̇o2peak) obtained during cycle exercise: Hi-Fit n = 9, V̇o2peak ≥ 56.1 ± 3.4 mL·kg-1·min-1 versus Avg-Fit n = 9, V̇o2peak ≤ 35.7 ± 4.9 mL·kg-1·min-1. On the second day, diaphragm fatigue was assessed before and after constant load exercise test to exhaustion. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess diaphragm fatigue by measurement of transdiaphragmatic twitch pressure (Pdi,tw). Both groups exercised at >90% of V̇o2peak for a similar duration (Hi-Fit: 546.1 ± 177.8 vs. Avg-Fit: 559.3 ± 175.0 s, P = 0.9). Diaphragm fatigue was defined as a ≥15% reduction in Pdi,tw, approximately two times greater than the coefficient of variation. The mean group average reduction in Pdi,tw following exercise in the Hi-Fit (17.5%) and Avg-Fit groups (12.2%) was not different between groups (P = 0.2). The Hi-Fit group performed exercise at a higher absolute work rate that elicited significantly greater ventilatory work and inspiratory muscle force output. The Hi-Fit group did not experience greater fatigue compared with the Avg-Fit group, which we attribute to a greater reliance on accessory respiratory muscle recruitment, to training-induced increases in the aerobic capacity of the diaphragm, or a combination of the two. In summary, aerobic fitness is not predictive of exercise-induced diaphragm fatigue in healthy females.NEW & NOTEWORTHY We hypothesized that females with a high aerobic capacity would be resistant to exercise-induced diaphragm fatigue relative to healthy but untrained females. We assessed the pressure generated by the diaphragm following exhaustive exercise by stimulating the phrenic nerves. The magnitude and incidence of fatigue were similar between groups. Despite having higher ventilatory demands during exercise highly trained females were resistant to greater diaphragm fatigue. Aerobic fitness is not predictive of exercise-induced diaphragm fatigue in females.

Improvements of the shape and strength of the diaphragm after endoscopic lung volume reduction

RationaleEndoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised...

Clinical Utility of Chest Sonography in Chronic Obstructive Pulmonary Disease Patients Focusing on Diaphragmatic Measurements.

There are many methods of evaluating diaphragmatic function, including trans-diaphragmatic pressure measurements, which are considered the key rule of diagnosis. We studied the clinical usefulness of chest ultrasonography in evaluating stable chronic obstructive pulmonary disease (COPD) patients and those in exacerbation, focusing on diaphragmatic measurements and their correlation with spirometry and other clinical parameters. In a prospective case-control study, we enrolled 100 COPD patients divided into 40 stable COPD patients and 60 patients with exacerbation. The analysis included 20 age-matched controls. In addition to the clinical assessment of the study population, radiological evaluation included chest radiographs and chest computed tomography. Transthoracic ultrasonography (TUS) was performed for all included subjects. Multiple A lines (more than 3) were more frequent in COPD exacerbation than in stable patients, as was the case for B-lines. TUS significantly showed high specificity, negative predictive value, positive predictive value, and accuracy in detecting pleural effusion, consolidation, pneumothorax, and lung mass. Diaphragmatic measurements were significantly lower among stable COPD subjects than healthy controls. Diaphragmatic thickness and excursion displayed a significant negative correlation with body mass index and the dyspnea scale, and a positive correlation with spirometry measures. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D showed lower diaphragmatic measurements (thickness and excursion). The TUS of COPD patients both in stable and exacerbated conditions and the assessment of diaphragm excursion and thickness by TUS in COPD patients and their correlations to disease-related factors proved informative and paved the way for the better management of COPD patients.

Acute inhibition of autophagy impairs maximal diaphragm force generation in old mice

Transdiaphragmatic pressure (Pdi) measurements are used to determine diaphragm force generation across various motor behaviors. Previous studies in the diaphragm muscle found selective age-related changes at fast-twitch fatigable motor units including increased susceptibility to neuromuscular transmission failure and denervation. Accordingly, age-related changes at diaphragm motor units predominantly impair the ability to accomplish higher force behaviors, and these aging effects are evident prior to the onset of muscle atrophy. Recent findings suggest that autophagy plays a critical role in the development of age-related neuromuscular dysfunction; however, the possible contribution of autophagy impairment to the maintenance of diaphragm force generation in old age is unknown. We hypothesized that inhibition of autophagy (using chloroquine) decreases diaphragm force-generating capacity (Pdi) in mice susceptible to age-related neuromuscular dysfunction. Adult male and female C57BL/6 mice at 16-28 months of age were randomized to receive a single intraperitoneal injection of 50 mg/kg of chloroquine or vehicle (n= 9 per treatment group) four hours before Pdi measurements, with the experimenter blinded. Pdi was measured during eupnea (room air breathing), exposure to hypoxia/hypercapnia (10% O 2 /5% CO 2 ), tracheal occlusion, spontaneous deep breaths (“sighs”) and during maximal activation elicited by bilateral phrenic nerve stimulation. Consistent with our hypothesis, there was an ~25% reduction in maximal Pdi in the chloroquine group (46 ± 12 cm H 2 O) compared to the vehicle control (61 ± 16 cm H 2 O; p < 0.05). There was no effect of chloroquine on Pdi during eupnea, hypoxia/hypercapnia, tracheal occlusion, or sigh behaviors. Acute inhibition of autophagy results in reduced maximal Pdi, consistent with that evident in old mice. Thus, we propose that autophagy impairment may be an important contributor to the reduced diaphragm force generation associated with aging. These findings help us further understand the mechanisms regulating age-related neuromuscular dysfunction and may serve as a foundation to develop novel treatments to mitigate aging effects. Support: NIH R01 AG057052. This is the full abstract presented at the American Physiology Summit 2023 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.

Occurrence and Effects on Weaning From Mechanical Ventilation of Intensive Care Unit Acquired and Diaphragm Weakness: A Pilot Study.

PurposeLimb intensive care unit (ICU)-acquired weakness (ICUAW) and ICU acquired diaphragm weakness (DW) occur frequently in mechanically ventilated (MV) patients; their coexistence in cooperative and uncooperative patients is unknown. This study was designed to (1) describe the co-occurrence of the two conditions (2) evaluate the impact of ICUAW and DW on the ventilator-free days (VFDs) at 28 days and weaning success, and (3) assess the correlation between maximal inspiratory pressure (MIP) and thickening fraction (TFdi) in patients with DW.MethodsThis prospective pilot study was conducted in a single-center on 73 critically ill MV patients. Muscle weakness was defined as a Medical Research Council score < 48 in cooperative patients or a bilateral mean simplified peroneal nerve test < 5.26 mV in uncooperative patients. Diaphragm dysfunction was defined as MIP < 30 cm H2O or as a TFdi < 29%. Weaning success was defined according to weaning according to a new definition (WIND).ResultsFifty-seven patients (78%) had ICUAW and 59 (81%) had DW. The coexistence of the two conditions occurred in 48 patients (65%), without association (χ2 = 1.06, p = 0.304). In the adjusted analysis, ICUAW was independently related to VFDs at 28-days (estimate difference 6 days, p = 0.016), and WIND (OR of 3.62 for having WIND different than short weaning), whereas DW was not. The linear mixed model showed a significant but weak correlation between MIP and TFdi (p < 0.001).ConclusionThis pilot study is the first to explore the coexistence of ICUAW and DW in both cooperative and uncooperative patients; a lack of association was found between DW and ICUAW when considering both cooperative and uncooperative patients. We found a strong correlation between ICUAW but not DW with the VFDs at 28 days and weaning success. A future larger study is warranted in order to confirm our results, and should also investigate the use of transdiaphragmatic twitch pressure measurement during bilateral anterior magnetic phrenic nerve stimulation for the diagnosis of DW.

On seasonal functional modeling under strong dependence, with applications to mechanically ventilated breathing activity

Breathing effort in mechanical ventilation is commonly estimated by airway pressure. More advanced methods involve transdiaphragmatic pressure measurements (Pdi) or surface electromyography (sEMG) of the respiratory muscles. To study whether inspiratory efforts may be predicted by the noninvasive sEMG method, a model is proposed for time series with a stochastically changing periodic component. The model can be interpreted as a functional time series or a process based on a state space representation, with a flexible temporal dependence structure in the parameter process and the residuals, including long memory, short memory or antipersistence. An application to Pdi and sEMG measurements shows the potential usefulness of the method in the context of monitoring patients undergoing mechanical ventilation.

NOT ALL THE PATIENTS PRESENTING WITH SHORTNESS OF BREATH HAVE HEART OR LUNG DISEASES

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The diaphragm is the primary muscle of respiration. Patients with bilateral diaphragmatic paralysis can present with dyspnea on exertion and be misdiagnosed as acute heart failure. Thyroid myopathy can involve diaphragm and require a high index of suspicion in patients with symptoms of heart failure with negative workup. CASE PRESENTATION: A 47-year-old male with a past medical history of coronary artery bypass grafting, and heart failure presented with dyspnea on exertion and orthopnea for one month. He was recently admitted with the same complaints and was discharged on an increased dose of furosemide with no response. On presentation, physical exam revealed orthopnea and bilateral decreased air entry at the lung bases. Oxygen saturation was 86% on room air. Arterial blood gas results showed pH 7.31, PCO2 61 on 100% FIO2. Laboratory data, including complete blood count and comprehensive metabolic profile, were unremarkable. EKG showed normal sinus rhythm and transthoracic echocardiogram showed an ejection fraction of 62%. Chest x-ray showed elevation of right hemidiaphragm (figure-1). He was treated with intravenous Lasix and BiPAP, but symptoms didn't improve, which prompted further workup, including a fluoroscopic "sniff test," which showed the paradoxical motion of both hemidiaphragm consistent with diaphragmatic paralysis. TSH level came back 306.0 µIU/ml, free T4 level was 0.32 ng/dL. Pulmonary function tests depicted mild obstructive and moderate restrictive lung disease (figure-2). Pt was treated with levothyroxine and was discharged on levothyroxine and trilogy after symptoms started improving. He showed significant improvement at one month's follow-up. DISCUSSION: Bilateral diaphragmatic paralysis primarily presents with shortness of breath on exertion and orthopnea within minutes of recumbency. The diagnosis is challenging as symptoms can be misinterpreted as a sign of heart failure; hence it is prudent to rule out acute heart failure. Severe hypothyroidism presenting as bilateral diaphragmatic paralysis is rarely reported in the literature, which decreases the activity of acid maltase, causing thyroid myopathy. The diagnosis can be made by paradoxical motion of hemidiaphragm on "sniff test," however, the measurement of trans-diaphragmatic pressure is the gold standard. The treatment depends on etiology and severity. Hypothyroidism should be treated promptly, and the use of small portable ventilators such as trilogy are helpful to assist breathing. In patients with intact phrenic nerve with no myopathy, phrenic nerve pacing can also be considered. CONCLUSIONS: Signs and symptoms of diaphragmatic paralysis can mimic heart failure. Physicians should maintain a high index of suspicion to workup for hypothyroidism and paralysis of the diaphragm in patients with typical presentation in the absence of cardiac or pulmonary etiology, as early diagnosis and treatment have good outcomes. REFERENCE #1: Thulaseedharan NK, Geetha P, Arathi N, et al. An unusual cause of orthopnoea-hashimoto's thyroiditis presenting as bilateral diaphragmatic palsy. Respiratory Medicine Case Reports. 2017;21:132-134. doi:10.1016/j.rmcr.2017.04.016 DISCLOSURES: No relevant relationships by Shaji Baig, source=Web Response No relevant relationships by Aneeba FAROOQi, source=Web Response No relevant relationships by Hafiz Jeelani, source=Web Response

Comprehensive Assessment of Respiratory Function, a Step towards Early Weaning from the Ventilator

Methods for assessing diaphragmatic function can be useful in determining the functional status of the respiratory system and can contribute to determining an individual's prognosis, depending on their pathology. They can also be a useful tool for making objective decisions regarding mechanical ventilation weaning and extubation. Esophageal and transdiaphragmatic pressure measurement, diaphragm ultrasound, diaphragmatic excursion, surface electromyography (sEMG) and some serum biomarkers are of increasing interest and use in clinical and intensive care settings to offer a more objective process for withdrawing mechanical ventilation; especially in the situation that we are experiencing with the increased demand for mechanical ventilation to treat patients with Covid-19-associated viral pneumonia. In this literature review, we updated the clinical and physiological indicators with more evidence to improve ventilator withdrawal techniques. We concluded that, to ensure successful extubation in a way that is useful, cost-effective, practical for health personnel and non-invasive for the patient, further studies of novel techniques such as surface electromyography should be implemented.

Phrenic nerve conduction study to diagnose unilateral diaphragmatic paralysis.

Unilateral diaphragmatic paralysis (UDP) has major clinical and etiological implications and, therefore, is important to diagnose. Lung function tests and invasive transdiaphragmatic pressure (Pdi) measurements are widely used to this end but, contrary to phrenic nerve conduction study (NCS), they require volitional maneuvers and/or may be poorly tolerated by patients. The purpose of this study was to compare the diagnostic accuracy of Pdi and phrenic NCS for UDP. We retrospectively reviewed 28 patients with suspected UDP. The diagnosis established during a multidisciplinary meeting was the reference standard. Phrenic NCS correlated well with Pdi (r = 0.82, P < .005), and the two tests showed good agreement (κ = 0.82, P < .005). Phrenic NCS and Pdi measurements both had 95% sensitivity, 87.5% specificity, 95% positive predictive, and 87.5% negative predictive values. Both tests were highly sensitive and specific. Phrenic NCS measurement is a simple, reproducible, noninvasive method whose results correlate well with Pdi and provide insight into the UDP mechanism. In the most difficult cases, combining lung function tests, respiratory muscle assessments, and phrenic NCS can help to establish the diagnosis.

Ultrafast ultrasound coupled with cervical magnetic stimulation for non-invasive and non-volitional assessment of diaphragm contractility.

Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non-volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons. Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown. Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure. This approach provides a novel fully non-invasive and non-volitional tool for the assessment of diaphragm contractility in humans. Measuring twitch transdiaphragmatic pressure (Pdi,tw ) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of Pdi requires invasive oesophageal and gastric catheter-balloons. Ultrafast ultrasound is a non-invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and Pdi,tw , and how these indices might be used to estimate Pdi,tw . CMS was performed in 13healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. Pdi,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1kHz framerate. Maximal diaphragm axial velocity (Vdi ,max ) and diaphragm thickening fraction (TFdi,tw ) were computed. Intra-session reliability was assessed. Repeated-measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra-session reliability was strong for Pdi,tw and Vdi,max and moderate for TFdi,tw . Vdi,max correlated with Pdi,tw in all subjects (0.64<ρ<1.00, R=0.75; all P < 0.05). TFdi,tw correlated with Pdi,tw in eight subjects only (0.85<ρ<0.93, R=0.69; all P<0.05). Coupling ultrafast ultrasound and CMS shows promise for the non-invasive and fully non-volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow-up of diaphragm contractility in clinical populations.

Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations

Background: Reference values derived from existing diaphragm ultrasound protocols are inconsistent, and the association between sonographic measures of diaphragm function and volitional tests of respiratory muscle strength is still ambiguous. Objective: To propose a standardized and comprehensive protocol for diaphragm ultrasound in order to determine lower limits of normal (LLN) for both diaphragm excursion and thickness in healthy subjects and to explore the association between volitional tests of respiratory muscle strength and diaphragm ultrasound parameters. Methods: Seventy healthy adult subjects (25 men, 45 women; age 34 ± 13 years) underwent spirometric lung function testing, determination of maximal inspiratory and expiratory pressure along with ultrasound evaluation of diaphragm excursion and thickness during tidal breathing, deep breathing, and maximum voluntary sniff. Excursion data were collected for amplitude and velocity of diaphragm displacement. Diaphragm thickness was measured in the zone of apposition at total lung capacity (TLC) and functional residual capacity (FRC). All participants underwent invasive measurement of transdiaphragmatic pressure (Pdi) during different voluntary breathing maneuvers. Results: Ultrasound data were successfully obtained in all participants (procedure duration 12 ± 3 min). LLNs (defined as the 5th percentile) for diaphragm excursion were as follows: (a) during tidal breathing: 1.2 cm (males; M) and 1.2 cm (females; F) for amplitude, and 0.8 cm/s (M) and 0.8 cm/s (F) for velocity, (b) during maximum voluntary sniff: 2.0 cm (M) and 1.5 cm (F) for amplitude, and 6.7 (M) cm/s and 5.2 cm/s (F) for velocity, and (c) at TLC: 7.9 cm (M) and 6.4 cm (F) for amplitude. LLN for diaphragm thickness was 0.17 cm (M) and 0.15 cm (F) at FRC, and 0.46 cm (M) and 0.35 cm (F) at TLC. Values for males were consistently higher than for females, independent of age. LLN for diaphragmatic thickening ratio was 2.2 with no difference between genders. LLN for invasively measured Pdi during different breathing maneuvers are presented. Voluntary Pdi showed only weak correlation with both diaphragm excursion velocity and amplitude during forced inspiration. Conclusions: Diaphragm ultrasound is an easy-to-perform and reproducible diagnostic tool for noninvasive assessment of diaphragm excursion and thickness. It supplements but does not replace respiratory muscle strength testing.

Trans-diaphragmatic pressure measurement as a prognostic factor in the Intensive Care Unit in dogs

In the last decade, attempts to improve the quality of the services provided to the critically ill patients in the Intensive Care Unit (ICU) are of great interest in human medicine. The aim of the majority of the clinical studies is the correlation of the survival rate of a critically ill patient with specific prognostic factors at the time of admission. The detailed assessment of a patient at admission in the ICU and during hospitalization seems to affect the management and the outcome. The main aim of this study was to evaluate if the trans-diaphragmatic pressure measurement can be a prognostic factor of the outcome in the ICU in dogs. Thirty-one dogs, 21 male and 10 female was included in this prospective, cohort study. Age, breed, sex, body weight and clinical diagnosis were recorded. The type of admission, the mentation status, physiological and biochemical parameters were measured at the admission of the dog in the ICU. All the variables were assessed over the first 24 hours following ICU admission. The animals were allocated into sixgroups: peritonitis/intra-abdominal surgery, intra-thoracic surgery, respiratory disease, neurologic disease, neoplasia, and systematic disease. The trans-diaphragmatic pressure (Pdi) was measured under the same anesthetic level in all animals with two oesophageal balloon catheters. The most frequent problem for admission in ICU was peritonitis (5/31). Seventeen out of 31 were admitted in acute status while 14/31 had a chronic problem. Mean±standard deviation of Pdi was 10.7±5.6 mmHg and of lactate concentration 2.3±1.2 mmol/L. Both, they can predict outcome (p=0.071 and p=0.076, respectively). Seven out of 31 dogs died, 2 were euthanized and 22 were discharged from the ICU after hospitalization. The technique of Pdi measurement with balloon catheters can be successfully applied in dogs in the ICU. Pdi measurement, as well as lactate concentration may be used as prognostic indicators for the outcome, in dogs in the ICU. However, a bigger sample size is need to support these findings.

Validation of a Proposed Algorithm for Assistance Titration During Proportional Assist Ventilation With Load-Adjustable Gain Factors

The present study aimed to validate a recently proposed algorithm for assistance titration during proportional assist ventilation with load-adjustable gain factors, based on a noninvasive estimation of maximum inspiratory pressure (peak Pmus) and inspiratory effort (pressure-time product [PTP] peak Pmus). Retrospective analysis of the recordings obtained from 26 subjects ventilated on proportional assist ventilation with load-adjustable gain factors under different conditions, each considered as an experimental case. The estimated inspiratory output (peak Pmus) and effort (PTP-peak Pmus) were compared with the actual-determined by the measurement of transdiaphragmatic pressure- and the derived PTP. Validation of the algorithm was performed by assessing the accuracy of peak Pmus in predicting the actual inspiratory muscle effort and indicating the appropriate level of assist. In the 63 experimental cases analyzed, a limited agreement was observed between the estimated and the actual inspiratory muscle pressure (-11 to 10 cm H2O) and effort (-82 to 125 cm H2O × s/min). The sensitivity and specificity of peak Pmus to predict the range of the actual inspiratory effort was 81.2% and 58.1%, respectively. In 49% of experimental cases, the level of assist indicated by the algorithm differed from that indicated by the transdiaphragmatic pressure and PTP. The proposed algorithm had limited accuracy in estimating inspiratory muscle effort and with indicating the appropriate level of assist.

Acute Impact of Disrupting BDNF/TrkB Signaling on Diaphragm Muscle Force Generation across Motor Behaviors

Brain‐derived neurotrophic factor (BDNF) binds with high affinity to tropomyosin‐related kinase receptor subtype B (TrkB), and plays an important role in neuromuscular junction (NMJ) function (regulating neuromuscular transmission and muscle innervation). We previously showed impaired neuromuscular transmission following acute inhibition of TrkB kinase activity in TrkBF616A mice harboring a point mutation that renders the kinase domain susceptible to inhibition by 1NMPP1 treatment. Neuromuscular transmission failure is expected to predominantly affect the ability of more fatigable motor units to generate force and thus primarily impair higher force motor behaviors. Accordingly, we hypothesized that acute administration of 1NMPP1 will impair the ability of the diaphragm muscle to accomplish higher force behaviors in adult, 6‐month old TrkBF616A mice. Transdiaphragmatic pressure (Pdi) measurements were conducted across a range of motor behaviors in lightly anesthetized mice during eupnea, exposure to hypoxia (10% O2)/hypercapnia (5% CO2), tracheal occlusion, spontaneous deep breaths (“sighs”) and during maximal activation elicited by bilateral phrenic nerve stimulation. Adult male and female TrkBF616A mice at 6 months were injected with 1NMPP1 or vehicle (DMSO) one hour prior to Pdi measurements. The Pdi generated during eupnea and hypoxia/hypercapnia was ~8 cm H20 compared to ~70 cm H20 during maximal stimulation. There was a significant reduction in Pdi during maximal force with bilateral phrenic nerve stimulation in the 1NMPP1 group compared to the vehicle control (p=0.01). There was no effect of 1NMPP1 on Pdi during eupnea, hypoxia/hypercapnia, tracheal occlusion, or sigh behaviors. The reduction in Pdi is generally similar to the impairment in neuromuscular transmission consistent with a predominant effect on motor units innervating fast‐twitch fatigable muscle fibers in the diaphragm muscle. Thus, impaired trophic BDNF/TrkB signaling can be expected to limit the range of motor behaviors accomplished by the diaphragm muscle and may be an important contributor to neuromuscular dysfunction.Support or Funding InformationThis study was supported by NIH grant R01 AG057052.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Assessment of human diaphragm function by ultrasounds

Thoracic ultrasound can provide a non-invasive technique for human diaphragm functional assessment, which can be used as an alternative to traditional, more challenging, and uncomfortable methods, such as transdiaphragmatic pressure measurement, fluoroscopic sniff test, nerve conduction studies, and electromyography. The variables that can be assessed using ultrasounds are (1) the static measurement of the end-expiratory diaphragm thickness (Tdi), (2) the dynamic evaluation of the of inspiratory to the expiratory diaphragm thicknesses, reported as the thickening ratio or thickening fraction (TF), and (3) the diaphragmatic excursion. The measurements of Tdi and TF are performed by placing a high-frequency linear probe at the level of the zone of apposition, while diaphragm excursion is measured using a curvilinear probe placed in the subcoastal region and recording diaphragm movements in the M-mode. Intra- and inter-observer reliabilities of the measurement of Tdi and TF are high, and ultrasound estimates of Tdi are correlated to direct anatomical measurements. Tdi can be used to monitor the evolution of diaphragm weakness. The reduced values of TF are associated with diaphragmatic paresis. Diaphragm excursion is sensitive to changes in the respiratory pattern, related to diaphragm’s volume generating capacity, and can be used to identify diaphragm weakness. In intubated patients, diaphragm excursion is related to weaning outcome.

Effect of diaphragm fatigue on subsequent exercise tolerance in healthy men and women.

Women are more resistant to diaphragmatic fatigue (DF) and experience an attenuated inspiratory muscle metaboreflex relative to men. The effects of such sex-based differences on whole body exercise tolerance are yet to be examined. It was hypothesized that DF induced prior to exercise would cause less of a reduction in subsequent exercise time in women compared to men. Healthy men ( n = 9, age = 24 ± 3 yr) and women ( n = 9, age = 24 ± 3 yr) completed a maximal incremental cycle test on day 1. On day 2, subjects performed isocapnic inspiratory pressure-threshold loading (PTL) to task failure followed by a constant load submaximal time-to-exhaustion (TTE) exercise test at 85% of the predetermined peak work rate. On day 3, subjects performed the same exercise test without prior induced DF. Days 2 and 3 were randomized and counterbalanced. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess DF by measurement of transdiaphragmatic twitch pressure ( Pdi,tw). A similar degree of DF was produced in both sexes following PTL [ Pdi,tw (% change from baseline): M = -24.6 ± 7.8%, W = -23.1 ± 5.4%; P = 0.54)]. There was a significant reduction in TTE with prior induced DF compared with the control condition in both men (10.9 ± 3.5 min vs. 13.0 ± 3.2 min, P = 0.05) and women (10.1 ± 2.4 min vs. 12.2 ± 3.3 min, P = 0.03) that did not differ in magnitude between the sexes (M = -15.8 ± 19.5%, W = -14.5 ± 19.2%, P = 0.89). In conclusion, DF negatively and equally impairs exercise tolerance independent of sex. NEW & NOTEWORTHY Women are more resistant to diaphragmatic fatigue (DF) relative to men. The effect of DF on exercise tolerance is currently being debated. Our findings show that DF negatively and equally affects exercise tolerance in healthy men and women. Mechanisms beyond the inspiratory muscle metaboreflex (e.g., dyspnea, central fatigue, breathing pattern) may explain the absence of a sex-based difference.

Functional Impact of Diaphragm Muscle Sarcopenia in Fischer 344 Rats

The diaphragm muscle (DIAm) is the primary inspiratory muscle responsible for force generation across a range of ventilatory and higher force airway clearance behaviors throughout life. Our laboratory has previously reported DIAm sarcopenia, the age‐related atrophy and weakening of skeletal muscle, in multiple rodent models. Interestingly, in Fischer 344 rats, there is an increase in body mass from 6 to 24 months of age, which is greater in females (~140%) than in males (~110%), suggesting potential sex‐related differences in the manifestation of sarcopenia. Transdiaphragmatic pressure (Pdi) measurements provide information about force generation in vivo across a range of motor behaviors. The purpose of this study was to evaluate if there are sex‐related differences in DIAm sarcopenia, and if such differences translate to a functional impact on Pdi generation. We hypothesized that because of differences in weight gain, DIAm sarcopenia is more pronounced in male vs. female Fischer 344 rats, and that there is a greater impact of sarcopenia on maximum Pdi generated by bilateral phrenic nerve stimulation (Pdimax). Since Pdi generated across a range of ventilatory motor behaviors only requires &lt;50% Pdimax, we also hypothesize that sarcopenia does not impair Pdi generation during ventilatory behaviors. Compared to 6‐month old rats, DIAm sarcopenia was apparent in ‐24‐month old rats of both sexes with a 30% reduction in maximum specific force. There was also a ~20% decrease in the cross‐sectional area of type IIx and/or IIb fibers with age, and this reduction was more pronounced in male rats. Thus, these mixed results do not entirely support our hypothesis of more pronounced DIAm sarcopenia in male rats. However, DIAm sarcopenia was associated with a ~30% decrease in Pdimax that was comparable between male and female rats. Importantly, the Pdi generated during ventilatory behaviors was unaffected by DIAm sarcopenia, even during more forceful ventilatory efforts induced by complete oropharyngeal airway occlusion. Although ventilatory behaviors are preserved with aging, a reduction in Pdimax indicates an impaired ability of the DIAm to generate higher force expulsive airway clearance behaviors necessary for maintaining airway patency.Support or Funding InformationNIH R01‐AG044615 and T32‐HL105355This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sensory-mechanical effects of a dual bronchodilator and its anticholinergic component in COPD

This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14±0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): “unpleasantness of breathing” fell 0.8±1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise.

Compensatory effects following unilateral diaphragm paralysis

Injury to nerves innervating respiratory muscles such as the diaphragm muscle results in significant respiratory compromise. Electromyography (EMG) and transdiaphragmatic pressure (Pdi) measurements reflect diaphragm activation and force generation. Immediately after unilateral diaphragm denervation (DNV), ventilatory behaviors can be accomplished without impairment, but Pdi generated during higher force non-ventilatory behaviors is significantly decreased. We hypothesized that 1) the initial reduction in Pdi during higher force behaviors after DNV is ameliorated after 14 days, and 2) changes in Pdi over time after DNV are associated with concordant changes in contralateral diaphragm EMG activity and ventilatory parameters. In adult male rats, the reduced Pdi during occlusion (∼40% immediately after DNV) was ameliorated to ∼20% reduction after 14 days. Contralateral diaphragm EMG activity did not significantly change immediately or 14days after DNV compared to the pre-injury baseline for any motor behavior. Taken together, these results suggest that over time after DNV compensatory changes in inspiratory related muscle activation may partially restore the ability to generate Pdi during higher force behaviors.

A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome.

ObjectivesWe aimed to develop a more representative model for neonatal congenital diaphragmatic hernia repair in a large animal model, by creating a large defect in a fast-growing pup, using functional pulmonary and diaphragmatic read outs.BackgroundGrafts are increasingly used to repair congenital diaphragmatic hernia with the risk of local complications. Growing animal models have been used to test novel materials.Methods6-week-old rabbits underwent fiberoptic intubation, left subcostal laparotomy and hemi-diaphragmatic excision (either nearly complete (n = 13) or 3*3cm (n = 9)) and primary closure (Gore-Tex patch). Survival was further increased by moving to laryngeal mask airway ventilation (n = 15). Sham operated animals were used as controls (n = 6). Survivors (90 days) underwent chest X-Ray (scoliosis), measurements of maximum transdiaphragmatic pressure and breathing pattern (tidal volume, Pdi). Rates of herniation, lung histology and right hemi-diaphragmatic fiber cross-sectional area was measured.ResultsRabbits surviving 90 days doubled their weight. Only one (8%) with a complete defect survived to 90 days. In the 3*3cm defect group all survived to 48 hours, however seven (78%) died later (16–49 days) from respiratory failure secondary to tracheal stricture formation. Use of a laryngeal mask airway doubled 90-day survival, one pup displaying herniation (17%). Cobb angel measurements, breathing pattern, and lung histology were comparable to sham. Under exertion, sham animals increased their maximum transdiaphragmatic pressure 134% compared to a 71% increase in patched animals (p<0.05). Patched animals had a compensatory increase in their right hemi-diaphragmatic fiber cross-sectional area (p<0.0001).ConclusionsA primarily patched 3*3cm defect in growing rabbits, under laryngeal mask airway ventilation, enables adequate survival with normal lung function and reduced maximum transdiaphragmatic pressure compared to controls.