Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to diverse modes of assisted ventilation. Conventional mechanical ventilators depend on flow sensors and pneumatic pressure and controllers to complete the respiratory cycle. Neurally adjusted ventilatory assist (NAVA) is a new form of assisted ventilation in recent years, which monitors the electrical activity of the diaphragm (EAdi) to provide an appropriately level of pressure support. And EAdi is the best available signal to sense central respiratory drive and trigger ventilatory assist. Unlike other ventilation modes, NAVA breathing instructions come from the center. Therefore, NAVA have the synchronous nature of the breaths and the patient-adjusted nature of the support. Compared with traditional ventilation mode, NAVA can efficiently unload respiratory muscles, relieve the risk of ventilator-induced lung injury (VILI), improve patient-ventilator coordination, enhance gas exchange, increase the success rate of weaning, etc. This article reviews the research progress of NAVA in order to provide theoretical guidance for clinical applications.
Humans ; Interactive Ventilatory Support ; Respiration, Artificial ; Positive-Pressure Respiration ; Diaphragm/physiology* ; Respiratory Muscles/physiology*

OBJECTIVE: To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction. METHODS: Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting. RESULTS: In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05). CONCLUSION Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.
Rats ; Male ; Animals ; Diaphragm/metabolism* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Rats, Sprague-Dawley ; Phosphorylation ; Muscle Contraction/physiology* ; Endoplasmic Reticulum ; Sepsis/metabolism*

PURPOSE: Studies on the physiology of the transposed stomach as an esophageal substitute in the form of a gastric pull-up or a gastric tube in children are limited. We conducted a study of motility and the pH of gastric esophageal substitutes using manometry and 24-hour pH measurements in 10 such patients. METHODS: Manometry and 24 hour pH studies were performed on 10 children aged 24 to 55 months who had undergone gastric esophageal replacement. RESULTS: Six gastric tubes (4, isoperistaltic; 2, reverse gastric tubes) and 4 gastric pull-ups were studied. Two gastric tubes and 4 gastric pull-ups were transhiatal. Four gastric tubes were retrosternal. The mean of the lowest pH at the midpoint of the substitute was 4.0 (range, 2.8–5.0) and in the stomach remaining below the diaphragm was 3.3 (range, 1.9–4.2). In both types of substitute, the difference between the peak and the nadir pH recorded in the intra-thoracic and the sub-diaphragmatic portion of the stomach was statistically significant (p < 0.05), with the pH in the portion below the diaphragm being lower. The lowest pH values in the substitute and in the remnant stomach were noted mainly in the evening hours whereas the highest pH was noted mainly in the morning hours. All the cases showed a simultaneous rise in the intra-cavitatory pressure along the substitute while swallowing. CONCLUSION: The study suggested a normal gastric circadian rhythm in the gastric esophageal substitute. Mass contractions occurred in response to swallowing. The substitute may be able to effectively clear contents.
Child* ; Circadian Rhythm ; Deglutition ; Diaphragm ; Gastric Stump ; Humans ; Hydrogen-Ion Concentration* ; Manometry* ; Physiology ; Stomach

Background: Neural respiratory drive (NRD) using diaphragm electromyography through an invasive transesophageal multi-electrode catheter can be used as a feasible clinical physiological parameter in patients with chronic obstructive pulmonary disease (COPD) to provide useful information on the treatment response. However, it remains unknown whether the surface diaphragm electromyogram (EMGdi) could be used to identify the deterioration of clinical symptoms and to predict the necessity of hospitalization in acute exacerbation of COPD (AECOPD) patients. Methods: COPD patients visiting the outpatient department due to acute exacerbation were enrolled in this study. All patients who were subjected to EMGdi and classical parameters such as spirometry parameters, arterial blood gas analysis, COPD assessment test (CAT) score, and the modified early warning score (MEWS) in outpatient department, would be treated effectively in the outpatient or inpatient settings according to the Global Initiative for Chronic Obstructive Lung Disease guideline. When the acute exacerbation of the patients was managed, all the examination above would be repeated. Results: We compared the relationships of admission-to-discharge changes (Δ) in the normalized value of the EMGdi, including the change of the percentage of maximal EMGdi (ΔEMGdi%max) and the change of the ratio of minute ventilation to the percentage of maximal EMGdi (ΔVE/EMGdi%max) with the changes of classical parameters. There was a significant positive association between ΔEMGdi%max and ΔCAT, ΔPaCO, and ΔpH. The change (Δ) of EMGdi%max was negatively correlated with ΔPaO/FiOin the course of the treatment of AECOPD. Compared with the classical parameters including forced expiratory volume in 1 s, MEWS, PaO/FiO, the EMGdi%max (odds ratio 1.143, 95% confidence interval 1.004-1.300) has a higher sensitivity when detecting the early exacerbation and enables to predict the admission of hospital in the whole cohort. Conclusions The changes of surface EMGdi parameters had a direct correlation with classical measures in the whole cohort of AECOPD. The measurement of NRD by surface EMGdi represents a practical physiological biomarker, which may be helpful in detecting patients who should be hospitalized timely.
Diaphragm ; physiopathology ; Electromyography ; methods ; Forced Expiratory Volume ; physiology ; Hospitalization ; Humans ; Pulmonary Disease, Chronic Obstructive ; metabolism ; physiopathology ; Spirometry ; Vital Capacity ; physiology

OBJECTIVETo explore the diaphragmatic toxicity in doxorubicin (DOX)-treated rats and the related mechanisms, as well as the effects of Shengmai Injection (SMI, ) on the diaphragmatic dysfunction.

METHODSThirty Sprague-Dawley male rats were randomly divided into three groups: control, DOX-treated and DOX+SMI treated groups. DOX was given to rats in DOX and DOX+SMI groups in 6 equal doses [2.5 mg/kg, intraperitoneal injection (i.p.)], on alternate days, over a period of 2 weeks for a cumulative dose of 15 mg/kg. SMI was given to DOX+SMI rats in 12 doses (3 mL/kg, i.p.) for a period of 2 weeks before the administration of DOX and 2 weeks during the administration of DOX. The rats in the control group received equal volume of normal saline. Subsequently, the twitch and tetanic characteristics and force-frequency relationships, and the malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activities, as well as the mRNA content and proteins of inducible nitric oxide synthase (iNOS) were determined.

RESULTSThe DOX-treated rats had decreased the peak twitch tension (Pt), maximal tetanic tension (P0) and force-frequency relationship as compared with the control rats (P<0.01), while the diaphragm contractility in rats treated with SMI were significantly higher than that in DOX-treated rats (P<0.01). The DOX-treated rats had increased MAD levels and decreased SOD activities (P<0.05), and SMI decreased the MDA levels and increased the SOD activities in DOX-treated rats (P<0.05). Ultrastructure of diaphragm in the DOX-treated rats revealed typical alterations including fracture of diaphragm fibers, and edema and degeneration of mitochondria; these changes were relieved by SMI treatment. The mRNA content and protein of iNOS in DOX-treated rats were remarkably higher than those in control rats (P<0.01), while SMI decreased the mRNA expression level of iNOS in DOX-treated rats (P<0.05).

CONCLUSIONSLipid peroxidation is responsible for DOX-induced diaphragm toxicity. SMI protects diaphragm muscles and their function from DOX impairment, and these beneficial effects may be somehow correlated with the decrease in expression of iNOS and lipid peroxidation.

Animals ; Biomechanical Phenomena ; drug effects ; Blotting, Western ; Diaphragm ; drug effects ; pathology ; physiology ; ultrastructure ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; In Vitro Techniques ; Injections ; Male ; Malondialdehyde ; metabolism ; Muscle Contraction ; drug effects ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Oxidative Stress ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

In practice of forensic medicine, potential disease can be associated with fatal asphyxia in restraint position. Research has demonstrated that nitric oxide (NO) and nitric oxide synthase (NOS) are plentifully distributed in skeletal muscle, contributing to the regulation of contractile and relaxation. In the current study, respiratory functions, indices of diaphragmatic biomechanical functions ex vivo, as well as NO levels in serum, the expressions of diaphragmatic inducible NOS (iNOS) mRNA, and the effects of L-NNA on contractility of the diaphragm were observed in sepsis induced by cecal ligation and puncture (CLP) under the condition of restraint position. The results showed that in the CLP12-18h rats, respiratory dysfunctions; indices of diaphragmatic biomechanical functions (Pt, +dT/dt(max), -dT/dt(max), CT, Po, force over the full range of the force-frequency relationship and fatigue resistance) declined progressively; the NO level in serum, and iNOS mRNA expression in the diaphragm increased progressively; force increased significantly at all stimulation frequencies after L-NNA pre-incubation. Restraint position 1 h in CLP12 h rats resulted in severe respiratory dysfunctions after relative stable respiratory functions, almost all the indices of diaphragmatic biomechanical functions declined further, whereas little change took place in NO level in serum and diaphragmatic iNOS mRNA expression; and the effects of L-NNA were lack of statistical significance compared with those of CLP12 h, but differed from CLP18 h group. These results suggest that restraint position and sepsis act together in a synergistic manner to aggravate the great reduction of diaphragmatic contractility via, at least in part, the negative modulation of NO, which may contribute to the pathogenesis of positional asphyxia.
Animals ; Asphyxia ; Diaphragm/physiology* ; Muscle Contraction ; Muscle, Skeletal ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase ; Nitric Oxide Synthase Type II ; Rats ; Respiration Disorders ; Restraint, Physical ; Sepsis

OBJECTIVETo observe the effects of neurally adjusted ventilatory assist (NAVA) on the patient-ventilator synchrony, gas exchange, and ventilatory parameters in preterm infants with respiratory distress syndrome (RDS) during mechanical ventilation.

METHODSTen preterm infants with RDS received mechanical ventilation in NAVA mode for 60 minutes and in synchronized intermittent mandatory ventilation (SIMV) mode for 60 minutes, and the two modes were given in a random order. The vital signs, patient-ventilator synchrony, blood gas values, and ventilatory parameters were compared between the two ventilation modes.

RESULTSInspiratory trigger delay was significantly shorter with NAVA than with SIMV (P<0.05). There were no significant differences in arterial pH, PaCO2, PaO2 and PaO2/FiO2 between the two modes. The spontaneous respiratory rate, peak inspiratory pressure (PIP), electrical activity of the diaphragm and work of breathing were significantly lower in NAVA than in SIMV (P<0.05).

CONCLUSIONSCompared with SIMV, NAVA appears to improve patient-ventilator synchrony, decrease PIP, and reduce diaphragmatic muscle load and work of breathing in preterm infants with RDS during mechanical ventilation.

Diaphragm ; physiology ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Respiration, Artificial ; methods ; Respiratory Center ; physiology ; Respiratory Distress Syndrome, Newborn ; therapy

Diaphragmatic electromyographic (EMGdi) signal is a weak biological signal, which contains some significant physiological information of our body respiration system and is susceptible to strong electrocardiography (ECG) signal interference. Based on wavelet transform and theory of information entropy, a new wavelet energy entropy threshold algorithm to remove ECG interference is proposed in this paper. On the base of analysis of wavelet coefficients of each scale, the method sees the information of each scale as a single signal source, equalizes it byzones, and then divides the energy entropy into two categories (i. e., high energy entropy and low energy entropy) through the distribution characteristics of energy entropy of each zone to conduct absolute mean value threshold. In addition, the denoised signal is reconstructed by wavelet coefficients processed. The experimental results showed that the method removed the ECG signal in EMGdi effectively and reserved the available characteristics of EMGdi better.
Algorithms ; Artifacts ; Diaphragm ; physiology ; Electrocardiography ; methods ; Electromyography ; methods ; Entropy ; Humans ; Signal Processing, Computer-Assisted ; Wavelet Analysis

OBJECTIVE: To observe effects of restraint position on the changes of diaphragmatic mechanical characteristic in rats, and try to explore the role of nitric oxide (NO). METHODS: Rat model of restraint position was established. Rats were divided into control group, restraint position 12h and 24h groups. The markers of respiratory functions in vivo and the biomechanical markers of diaphragmatic characteristic ex vivo were evaluated. Serum NO levels were measured with spectrophotometry. The expressions of nNOS and iNOS mRNA in diaphragm were detected using RT-PCR. RESULTS: Compared with control group, respiratory rate, tidal volume and minute ventilation were significantly decreased in the restraint position 12h and 24h groups. Pt of diaphragm significantly decreased and force-generating capacity reduced at low frequency stimulation in 12h group. Force-generating capacity over the full range reduced at low and high frequency stimulation in 24h group. Pt of diaphragm in control and restraint position groups increased after L-NNA pre-incubation. Force-frequency relationship after L-NNA pre-incubation reduced in 24h group. NO level in serum increased significantly in the restraint position groups. Diaphragmatic nNOS mRNA expression was upregulated significantly in the restraint position groups. CONCLUSION Restraint position induces the decreasement of diaphragmatic contractility and the decreasement is mediated by NO from diaphragm or circulation blood.
Animals ; Biomechanical Phenomena ; Diaphragm/physiopathology* ; Male ; Muscle Contraction/physiology* ; Muscle Tonus/physiology* ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase/metabolism* ; Posture ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Respiration Disorders/physiopathology* ; Restraint, Physical ; Reverse Transcriptase Polymerase Chain Reaction

Animals ; Diaphragm ; physiopathology ; Electrophysiological Phenomena ; physiology ; Hypoxia ; physiopathology ; Male ; Rats ; Rats, Wistar ; Sleep Apnea Syndromes ; physiopathology