Inspiratory Contraction Research Articles

Hiccup-like Contractions in Mechanically Ventilated Patients: Individualized Treatment Guided by Transpulmonary Pressure.

Hiccups-like contractions, including hiccups, respiratory myoclonus, and diaphragmatic tremor, refer to involuntary, spasmodic, and inspiratory muscle contractions. They have been repeatedly described in mechanically ventilated patients, especially those with central nervous damage. Nevertheless, their effects on patient-ventilator interaction are largely unknown, and even more overlooked is their contribution to lung and diaphragm injury. We describe, for the first time, how the management of hiccup-like contractions was individualized based on esophageal and transpulmonary pressure measurements in three mechanically ventilated patients. The necessity or not of intervention was determined by the effects of these contractions on arterial blood gases, patient-ventilator synchrony, and lung stress. In addition, esophageal pressure permitted the titration of ventilator settings in a patient with hypoxemia and atelectasis secondary to hiccups and in whom sedatives failed to eliminate the contractions and muscle relaxants were contraindicated. This report highlights the importance of esophageal pressure monitoring in the clinical decision making of hiccup-like contractions in mechanically ventilated patients.

After-effects of thixotropic conditionings on operational chest wall and compartmental volumes of patients with Parkinson's disease.

Individuals with Parkinson’s disease (PD) present respiratory dysfunctions, mainly due to decreased chest wall expansion, which worsens with the course of the disease. These findings contribute to the restrictive respiratory pattern and the reduction in chest wall volume. According to literature, inspiratory muscle thixotropic conditioning maneuvers may improve lung volumes in these patients. The study aimed to determine the after-effects of respiratory muscle thixotropic maneuvers on breathing patterns and chest wall volumes of PD. A crossover study was performed with twelve patients with PD (8 males; mean age 63.9±8.8 years, FVC%pred 89.7±13.9, FEV1%pred 91.2±15, FEV1/FVC%pred 83.7±5.7). Chest wall volumes were assessed using OEP during thixotropic maneuvers. Increases in EIVCW (mean of 126mL, p = 0.01) and EEVCW (mean of 150mL, p = 0.005) were observed after DITLC (deep inspiration from total lung capacity) due to increases in pulmonary (RCp) and abdominal (RCa) ribcage compartments. Changes in ICoTLC (inspiratory contraction from TLC) led to significant EIVCW (mean of 224mL, p = 0.001) and EEVCW (mean of 229mL, p = 0.02) increases that were mainly observed in the RCp. No significant changes were found when performing DERV (deep expiration from residual volume) and ICoRV (Inspiratory contraction from RV). Positive correlations were also observed between the degree of inspiratory contraction during ICoTLC and EEVRCp (rho = 0.613, p = 0.03) and EIVRCp (rho = 0.697, p = 0.01) changes. Thixotropy conditioning of inspiratory muscles at an inflated chest wall volume increases EIVCW and EEVCW in the ten subsequent breaths in PD patients. These maneuvers are easy to perform, free of equipment, low-cost, and may help patients improve chest wall volumes during rehabilitation.

Abstract 10528: Exaggerated Inspiratory Muscle Metaboreflex in Heart Failure with Preserved Ejection Fraction

Introduction: Heart failure patients with preserved ejection fraction (HFpEF) may exhibit inspiratory muscle dysfunction potentially contributing to exercise intolerance. Activation of neural afferents in response to inspiratory muscle contraction (metaboreflex) elicits increases in mean arterial pressure (MAP) and leg vascular resistance (LVR) through enhanced sympathetic outflow leading to decreases in leg blood flow (LBF) in healthy humans. It is unknown if HFpEF patients exhibit exaggerated cardiovascular responses to inspiratory muscle metaboreflex activation. Hypothesis: We hypothesize that patients with HFpEF will exhibit a greater increase in MAP and LVR with a decrease in LBF during inspiratory muscle metaboreflex activation than controls. Methods: HFpEF patients (n=15, 10M/5W, 69±10 yrs; 33±4 kg/m2) and controls (n=14; 10M/4W; 70±8 yrs; 28±4 kg/m2) performed inspiratory resistive breathing tasks (IRBT) at 2% and 60% of their maximal inspiratory pressure. During the IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest and during the IRBTs, MAP was measured by photoplethysmography, venous norepinephrine was measured, LBF was measured by near-infrared spectroscopy and indocyanine green dye injections, and LVR was calculated. Results: During the 2% IRBT, there were no differences between groups in the changes from rest in MAP (HFpEF: 2±4 vs. CTL: 3±4 mmHg) or LBF (HFpEF: 1±14 vs. CTL: 1±12%) (both, p>0.05). During the 60% IRBT, venous norepinephrine increased from rest in HFpEF and controls (p<0.05), while no differences existed between groups (p>0.05). During the 60% IRBT, HFpEF patients, compared to controls, exhibited a greater increase from rest in MAP (HFpEF: 16±7 vs. CTL: 10±6 mmHg) and LVR (HFpEF: 76±45 vs. CTL: 32±19%) coupled with a greater decrease in LBF (HFpEF: -32±14 vs. CTL: -17±9%) (all, p<0.05). Conclusions: These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared to healthy individuals. These findings have important implications for the integrative physiology of exercise in HFpEF patients.

Pathophysiology of pulmonary function anomalies in COVID-19 survivors.

Coronavirus disease 2019 (COVID-19) is a disease caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-​2), and the predisposing and protecting factors have not been fully elucidated. COVID-19 primarily impacts the respiratory system, and can result in mild illness or serious disease leading to critical illness requiring admission to the intensive care unit due to respiratory failure. After hospital discharge, the more commonly described pulmonary function anomalies are alterations in diffusing capacity and the loss of lung volume. Reduction of inspiratory muscle contraction may also be underestimated. This article will focus on the pathophysiology of pulmonary function anomalies in COVID-19 survivors. We will discuss current advances and provide future directions and also present our perspective on this field.

Diaphragmatic ultrasound and pulmonary functions evaluation in thyroid patients: a case-control study

BackgroundDyspnea is a frequent symptom among patients with thyroid disorders. However, its actual causative mechanism is not clear. The diaphragm is the main inspiratory muscle and contraction of the diaphragm is essential for breathing, so any disorder that interferes with contractile muscle function can cause diaphragm dysfunction which is associated with dyspnea. The objective of study is to assess the effect of thyroid disorders on diaphragm excursion and thickness.ResultsDiaphragmatic excursion during tidal, deep, and sniff respiration were significantly decreased in patients with thyroid disorder in comparison to control and significantly decreased in hypothyroid patients (right tidal 1.42 ± 0.29, right deep respiration 5.07 ± 0.72, and sniff 2.15 ± 0.26 cm) than hyperthyroid patients (right tidal 1.61 ± 0.34, right deep respiration 5.63 ± 0.50, and sniff 2.67 ± 0.27 cm) and than the control group (right tidal 2.17 ± 0.27, right deep respiration 6.63 ± 0.33, right sniff 2.89 ± 0.19 cm). Diaphragmatic thickness at end tidal inspiration was significantly decreased in patients with thyroid disorder in comparison to control (p value < 0.05). There was negative correlation between diaphragmatic excursion and duration of disease.ConclusionDiaphragmatic excursion and thickness are affected in hypothyroidism compared to hyperthyroidism and control groups. There is significant negative correlation between diaphragmatic excursion and duration of disease in patients’ group. Respiratory symptoms are more frequent in hypothyroid patients.

Intradermal injection for hiccup therapy in the Emergency Department

Hiccup is a condition caused by involuntary contraction of inspiratory muscles, especially the diaphragm. Although it is generally considered as a physiological.response, if hiccup persists for a long time, it can lead to many undesirable conditions such as depression, weight loss, insomnia, and fatigue. A 35-year-old male patient was admitted to our emergency department with hiccup lasting for 15 h. He had a history of several hiccup attacks. Classical non-pharmacological and pharmacological therapies were used to treat the condition without any response. As an alternative method, an intradermal injection was applied. A mixture of thiocolchicoside and lidocaine was administered intradermally to a depth of 1–3 mm at the epigastric region and adjacent to the sternocleidomastoid muscle. The patient's hiccup ended after the intradermal injection procedure. During 48 h of follow-up the hiccup attack did not develop again. No complications related to the process were detected. This is the first case in the literature demonstrating the use of intradermal injection to terminate hiccups. The intradermal injection approach can be administered in cases of hiccups that do not respond to medical treatment.

After-Effects of Thixotropic Maneuvers on Chest Wall and Compartmental Operational Volumes of Healthy Subjects Using Optoelectronic Plethysmography.

The volumes assessed by optoelectronic plethysmography (OEP) and based on a three-compartmental model provide an accurate breath-by-breath index of expiratory and inspiratory (ribcage muscles and diaphragm) muscle length. Thus, after performing thixotropic maneuvers, OEP may also provide evidence regarding the history-dependent properties of these muscles. We studied the after-effects of different thixotropic conditionings on chest wall (CW) and compartmental operational volumes of 28 healthy subjects (25.5 ± 2.2 years, FVC%pred 94.8 ± 5.5, and FEV1%pred 95.5 ± 8.9) using OEP. Conditionings were composed of inspiratory or expiratory contractions performed from total lung capacity (TLC) or residual volume (RV). The study protocol was composed of three consecutive contractions of the same maneuver, with 60 s of spontaneous breathing in between, and after-effects were studied in the first seven respiratory cycles of each contraction. Cumulative effects were also assessed by comparing the after-effects of each thixotropic maneuver. Inspiratory contractions performed from both TLC and RV acutely increased end-inspiratory (EIV) CW volumes (all p < 0.0001), mainly on both upper and lower ribcage compartments (i.e., non-diaphragmatic inspiratory muscles and diaphragm, respectively); while, expiratory contractions from RV decreased CW volumes (p < 0.0001) by reducing the upper ribcage and abdominal volumes (all p < 0.0001). The response of the thixotropic maneuvers did not present a cumulative effect. In healthy, the use of the three-compartmental model through OEP allows a detailed assessment of the diaphragm, inspiratory and expiratory muscle thixotropy. Furthermore, specific conditioning maneuvers led to thixotropy of the inspiratory ribcage, diaphragm, and expiratory muscles.

Respiratory muscle activation and action during voluntary cough in healthy humans

Cough is a defensive airway reflex consisting of a modified respiratory act which involves the sequential activation of several laryngeal and respiratory muscles. The contraction of the latter results in thoraco-abdominal volume variations in order to provide enough amount of air available, the operating volume (OV), to be expelled. Because both posture and OV could influence muscular activation and thoraco-abdominal displacements during voluntary cough, we aimed to verify if and how they play a role during inspiratory (ICP) and expiratory (ECP) cough phases, in terms of flow, volumes and surface electromyography activity (sEMG). In 10 healthy subjects, we measured sEMG of 7 muscles (scalene, sternocleidomastoid, parasternal, intercostal, diaphragm (assessed at the 8th intercostal space), external abdominal oblique and rectus abdominis) in supine and seated position during cough maneuvers performed at 4 different OV measured by opto-electronic plethismography: total lung capacity (TLC), functional residual capacity and two intermediate volumes. The amplitude of sEMG signals tended to be maximal at TLC (p < 0.005) during ICP in the neck and parasternal muscles and during ECP in abdominal muscles. Postures slightly affected only sEMG of the thoracic muscles. sEMG data were similar (p > 0.05) in the other OV, but cough peak flow increased with OV. Thoraco-abdominal volume variations during cough were unaffected by posture and OV as well, being predominantly thoracic (supine: 60 and 64%; seated: 68 and 69%, respectively during ICP and ECP).Our results suggest that voluntary cough OV or posture do not have an important effect on voluntary cough that seems more likely to be resulting from a motor mechanism that activates a synergetic antagonistic contraction of inspiratory and expiratory muscles leading to a specific thoraco-abdominal pattern, in which the rib cage is the predominant.

Preparation of Rhythmically-active In Vitro Neonatal Rodent Brainstem-spinal Cord and Thin Slice.

Mammalian inspiratory rhythm is generated from a neuronal network in a region of the medulla called the preBötzinger complex (pBC), which produces a signal driving the rhythmic contraction of inspiratory muscles. Rhythmic neural activity generated in the pBC and carried to other neuronal pools to drive the musculature of breathing may be studied using various approaches, including en bloc nerve recordings and transverse slice recordings. However, previously published methods have not extensively described the brainstem-spinal cord dissection process in a transparent and reproducible manner for future studies. Here, we present a comprehensive overview of a method used to reproducibly cut rhythmically-active brainstem slices containing the necessary and sufficient neuronal circuitry for generating and transmitting inspiratory drive. This work builds upon previous brainstem-spinal cord electrophysiology protocols to enhance the likelihood of reliably obtaining viable and rhythmically-active slices for recording neuronal output from the pBC, hypoglossal premotor neurons (XII pMN), and hypoglossal motor neurons (XII MN). The work presented expands upon previous published methods by providing detailed, step-by-step illustrations of the dissection, from whole rat pup, to in vitro slice containing the XII rootlets.

High-intensity inspiratory muscle training in bronchiectasis: A randomized controlled trial.

Inspiratory muscle training (IMT) enhances velocity of inspiratory muscle contraction and modifies inspiratory and expiratory time. This study aimed to examine the impact of high-intensity IMT (H-IMT) on exercise capacity in bronchiectasis. Forty-five patients were included. Lung function, respiratory muscle strength and endurance, exercise capacity, dyspnoea, fatigue and quality of life (QOL) were evaluated. Patients were randomized into two groups: H-IMT and control groups. Twenty-three patients underwent H-IMT for 8 weeks, using threshold loading with a target workload of maximal inspiratory pressure (MIP) of at least 70%, with 3-min cycles (as 2-min training: 1-min rest intervals) for 21 min. There was a total period of 14 min of loaded breathing and 7 min of recovery. The control group (n = 22) underwent low-intensity IMT at 10% of the initial MIP and was maintained at the same intensity until the end of the training. After training, both MIP and maximal expiratory pressure (MEP) and the incremental shuttle walk distance were increased in the H-IMT group compared with the control group (P < 0.05). There was a significant difference in constant threshold load, time and pressure-time units in the H-IMT group (P < 0.05) but not in the control group (P > 0.05). A significant decrease was found in fatigue in both groups (P < 0.05). The Leicester Cough Questionnaire social score for the H-IMT group decreased significantly after the treatment (P < 0.05). The H-IMT increased exercise capacity in patients with non-cystic fibrosis bronchiectasis. It has also positive effects on respiratory muscle strength and endurance, and social aspects of QOL.

Rabies: a medical perspective

Rabies is an acute neurological infection of humans and animals, caused by rabies virus and usually transmitted by animal bites. After an incubation period usually lasting weeks or longer, a variety of prodromal symptoms may occur. Encephalitic rabies (80% of cases) is associated with episodes of generalised arousal or hyperexcitability and hydrophobia, in which spasms involve the contraction of inspiratory muscles with swallowing. Paralytic rabies (in 20% of cases) is characterised by progressive lower motor neuron weakness. Laboratory investigations are important for confirming an ante mortem diagnosis of rabies. Cardiopulmonary and many other complications, including multiple organ failure, are common in aggressively managed rabies patients in critical care units. No effective therapy is available for rabies and survivors are uncommon. In contrast, preventative measures for rabies are highly effective after recognised exposures.

Correction of Paradoxical Ribcage Motion in Scoliosis by Noninvasive Ventilation.

Observational study of ribcage motion in scoliosis. To see whether noninvasive ventilation corrected paradoxical inward motion of the ribs during inspiration. Paradoxical inward motion of the ribs is observed after rib fractures, low cervical cord injury, and in chronic obstructive pulmonary disease. It is not well recognized in scoliosis and the mechanism in this group has not been studied. Linearized magnetometers were used to measure the diameter of the ribcage. Changes in diameter during tidal breathing were recorded during spontaneous ventilation and noninvasive ventilation in 10 subjects with idiopathic or congenital thoracic scoliosis. During spontaneous breathing, the median change in ribcage diameter during inspiration was -1.5 (range -2.3 to -0.8) cm. The median change in ribcage diameter during noninvasive ventilation was +0.5 (range -1.1 to +1.2) cm. Noninvasive ventilation improved paradoxical motion in all subjects, completely correcting it in six. Paradoxical inward motion of the ribcage is seen in some subjects with severe scoliosis. This abnormal motion is improved or abolished by noninvasive ventilation. Since noninvasive ventilation takes over the work of breathing from the respiratory muscles, we suggest that inspiratory muscle contraction causes distortion of part of the ribcage in scoliosis, probably because of the abnormal orientation of diaphragmatic muscle fibers. 2.

A V0 core neuronal circuit for inspiration

Breathing in mammals relies on permanent rhythmic and bilaterally synchronized contractions of inspiratory pump muscles. These motor drives emerge from interactions between critical sets of brainstem neurons whose origins and synaptic ordered organization remain obscure. Here, we show, using a virus-based transsynaptic tracing strategy from the diaphragm muscle in the mouse, that the principal inspiratory premotor neurons share V0 identity with, and are connected by, neurons of the preBötzinger complex that paces inspiration. Deleting the commissural projections of V0s results in left-right desynchronized inspiratory motor commands in reduced brain preparations and breathing at birth. This work reveals the existence of a core inspiratory circuit in which V0 to V0 synapses enabling function of the rhythm generator also direct its output to secure bilaterally coordinated contractions of inspiratory effector muscles required for efficient breathing.

Blood pressure response during normocapnic hyperpnoea is blunted in young women compared to men

We hypothesized that young women have a lower arterial blood pressure (BP) response to high inspiratory and expiratory muscle contractions with normocapnic hyperpnoea compared to age-matched men. To test this hypothesis, the cardiovascular response during voluntary normocapnic incremental hyperpnoea was evaluated in young women and compared to that of young men. An incremental respiratory endurance test (IRET) was performed as follows: target minute ventilation was initially set to 30% of the maximal voluntary ventilation (MVV12) and was increased by 10% MVV12 every 3min. The test was terminated when the subject could not maintain the target%MVV. Heart rate and mean arterial BP (MBP) were continuously recorded. The increase in MBP from the baseline (ΔMBP) during the IRET was lower in women than in men (ΔMBP, men: +32.1±4.6mmHg vs. women: +14.9±3.5mmHg at 8min during IRET). This result suggests that young women exhibit a blunted arterial BP response during high-speed inspiratory and expiratory muscle contractions with normocapnic hyperpnoea compared to young men.

Blood Pressure Response During Hyperpnoea Is Lower in Women Compared with Men

It has been reported that women exhibit less inspiratory muscle fatigue during exercise. Additionally, a recent study found a lower blood pressure response to resistive inspiratory muscle activity (high-resistance, low-speed inspiratory muscle contractions), indicating that women exhibit an attenuated inspiratory muscle metaboreflex compared to men. Another way to model the respiratory muscle metaboreflex is to measure the cardiovascular response to exercise-mimicking hyperpnoea (low-resistance, high-speed inspiratory and expiratory muscle contractions). It is hypothesized that women will have a lower cardiovascular response to low-resistance, high-speed inspiratory and expiratory muscle contractions. PURPOSE: To test this hypothesis, the cardiovascular response during voluntary normocapnic incremental hyperpnoea was evaluated in young women and age-matched men. METHODS: Healthy young subjects (8 men, 10 women) participated in this study. An incremental respiratory endurance test was performed as follows: target minute ventilation was initially set at 30% of maximal voluntary ventilation (MVV12) and was increased by 10% MVV12 every 3 min. The test was terminated when the subject could no longer maintain the target ventilation. Heart rate and arterial blood pressure (BP) were continuously measured. RESULTS: There was no significant difference in respiratory endurance time between women (11.6±0.6 min) and men (12.3±0.5 min). The change in mean arterial BP (MBP) during the incremental respiratory endurance test was significantly lower in women compared to men (women: 105.9±3.2 mmHg, men: 126.0±6.0 mmHg at 9 min). CONCLUSIONS: The data from the present study suggests that the respiratory muscle-induced metaboreflex is blunted in women compared to age-matched men.

1238 West Nile Encephalitis with suspected diaphragmatic dysfunction leading to sleep apnea with associated hypoventilation

Currently, there are no guidelines on the management of acute sleep disordered breathing in the ICU or inpatient setting. Here, we report a case in which an acute sleep medicine evaluation was utilized to treat a patient with West Nile Encephalitis and sleep related hypoventilation with suspected diaphragmatic weakness. This is an 82 yo male who presented with lethargy and dyspnea after a recent trip to El Salvador. Physical exam was significant for shallow, rapid respirations with mild use of accessory muscles and fluctuating mental status. Patient denied any history of lung disease or OSA but became progressively more somnolent with rising pCO2 levels. This prompted a sleep medicine consult to optimize PAP therapy as patient had declined elective intubation. Due to patient’s unstable condition, a bedside trial was performed in the Step Down Unit utilizing BIPAP with settings of 18/8 cmH20, PS 4 cmh20 and 2L O2. Results showed an AHI of 72 with evidence of worsening hypoventilation based on his pCO2 of 80 (ABG). However, this study was limited due to the inability to differentiate central from obstructive events given the available equipment. Concurrently, further workup for encephalopathy revealed presence of West Nile Encephalitis based on positive IgM antibodies in CSF. Upon review of additional studies, chest imaging was concerning for diaphragmatic dysfunction. This concern was corroborated by ultrasonography which, although of poor image quality, failed to show any significant inspiratory contraction of the R diaphragm. A repeat BIPAP trial was then performed utilizing a backup rate of 12 bpm with pressure of 16/10 cmH20 and 2L O2. Results showed an AHI of 15.7 with average O2 91.6%. In the days following, his pCO2 levels improved to 50. In conclusion, WNV-induced myositis vs phrenic neuropathy leads the differential for this patient’s diaphragmatic dysfunction/hypoventilation. Further testing is needed.

Inspiratory work capacity is more severely depressed than inspiratory muscle strength in patients with heart failure: Novel applications for inspiratory muscle training

BackgroundWe hypothesized that the ability to sustain maximal inspiratory pressure (SPImax) over time as a measure of work capacity may be more severely affected than inspiratory muscle strength (PImax) in patients with heart failure (HF). MethodsWe retrospectively investigated eighty patients with HF, NYHA II/III/ ambulatoryIV and a (mean±SD) LVEF 27±8%, and compared them to 25 healthy subjects (HS). During a maximal inspiratory manoeuvre from residual volume (RV) to total lung capacity, PImax was measured as the maximum mouth pressure at RV, inspiratory contraction time (ICT) as the time from RV to end of inspiration and SPImax as the area under a pressure-time curve using an electronic pressure manometer with designed-purpose software (Trainair®, Project Electronics Ltd., London, UK). Exercise capacity was assessed with cardiopulmonary exercise testing and the 6-minute walk test (6MWT). ResultsPatients achieved a (mean±SD) peak VO2=15.7±3.4ml/kg/min and 6MWT=338±88m. PImax, ICT and SPImax were reduced in HF pts at 75%***, 61%*** and 52%*** of HS, and correlated with NYHA (r=−0.485***), (r=−0.507**), (r=−0.500***), peakVO2 (r=0.501***), (r=0.655***), (r=0.508***) and 6MWT (r=0.477***), (r=0.345**), (r=0.530***), respectively (*p<0.05, **p<0.01, ***p<0.001). ConclusionPImax, ICT and SPImax were impaired in HF patients compared to HS and may be important determinants of exercise capacity. SPImax was severely depressed even in patients with relatively preserved PImax and should be considered as an additional target index for inspiratory muscle training. Equations are provided to predict SPImax in relation to age and exercise capacity in HF.

Janus kinase inhibition prevents cancer- and myocardial infarction-mediated diaphragm muscle weakness in mice.

Respiratory dysfunction is prevalent in critically ill patients and can lead to adverse clinical outcomes, including respiratory failure and increased mortality. Respiratory muscles, which normally sustain respiration through inspiratory muscle contractions, become weakened during critical illness, and recent studies suggest that respiratory muscle weakness is related to systemic inflammation. Here, we investigate the pathophysiological role of the inflammatory JAK1/3 signaling pathway in diaphragm weakness in two distinct experimental models of critical illness. In the first experiment, mice received subcutaneous injections of PBS or C26 cancer cells and were fed chow formulated with or without the JAK1/3 inhibitor R548 for 26 days. Diaphragm specific force was significantly reduced in tumor-bearing mice receiving standard chow; however, treatment with the JAK1/3 inhibitor completely prevented diaphragm weakness. Diaphragm cross-sectional area was diminished by ∼25% in tumor-bearing mice but was similar to healthy mice in tumor-bearing animals treated with R548. In the second study, mice received sham surgery or coronary artery ligation, leading to myocardial infarction (MI), and were treated with R548 or vehicle 1 h postsurgery, and once daily for 3 days. Diaphragm specific force was comparable between sham surgery/vehicle, sham surgery/R548 and MI/R548 groups, but significantly decreased in the MI/vehicle group. Markers of oxidative damage and activated caspase-3, mechanisms previously identified to reduce muscle contractility, were not elevated in diaphragm extracts. These experiments implicate JAK1/3 signaling in cancer- and MI-mediated diaphragm weakness in mice, and provide a compelling case for further investigation.

0434. Simulation of late inspiratory rise in airway pressure during pressure support ventilation

Late inspiratory rise in airway pressure (LIRAP, ΔPaw/Δt, Fig. ​Fig.1)1) caused by inspiratory muscle relaxation or expiratory muscle contraction is frequently seen during pressure support ventilation [1, 2], although the factors that modulate LIRAP are unknown. Figure 1 Objectives The aim of current study was to determine the factors related to LIRAP during PSV using a simulation lung model. Influence of inspiratory muscle relaxation was assessed under various combinations of lung models and ventilator settings. Influence of expiratory muscle contraction was assessed through its intervention at various time points during the inspiratory phase.

The Mechanisms of Compensatory Responses of the Respiratory System to Simulated Central Hypervolemia in Normal Subjects.

The compensatory responses of the respiratory system to simulated central hypervolemia (CHV) were investigated in 14 normal subjects. The central hypervolemia was caused by a short-time passive head-down tilt (HDT, -30°, 30 min). The results show that CHV increased the mechanical respiratory load and the airway resistance, slowed the inspiratory flow, increased the duration of the inspiratory phase, reduced the respiratory rate, but not changed the minute ventilation. CHV induced a significant rise in inspiratory swings of alveolar pressure (184%), based on the inspiratory occlusion pressure measurement. These changes indicate a compensatory increase in the inspiratory muscle contraction force. A stable level of minute ventilation during CHV was an effect of increased EMG activity of parasternal muscles more than twice (P<0.01). A contribution of the diaphragm and scalene muscles to ventilation during spontaneous breathing in HDT was reduced. An increase of genioglossus contractile activity during HDT contributed to the stabilization of airway patency. These results suggest that a coordinated modulation of inspiratory muscles activity allows preserving a constant level of minute ventilation during a short-time intrathoracic blood volume expansion. The mechanisms of respiratory load compensation seem to be mediated by afferent information from the lung and respiratory muscle receptors and from the segmentary reflexes and intrinsic properties of the muscle fibers.