Objective To investigate the expressions of ubiquitin-proteasome markers，including E2-14K，MAFbx，MuRF-1，and nuclear factor-κB（NF- κB） p50，in diaphragm of COPD rats，and their relationship with IL-17 level in diaphragm and serum in order to elucidate the potential mechanism of diaphragm atrophy. Methods Thirty healthy adult male SD rats were randomly divided into a model group （n=18） and a normal control group （n=12）. The COPD rat model was established by instillation of lipopolysaccharide （LPS） and exposure to cigarette smoke for 28 days. The protein levels of E2-14K，MAFbx，MuRF-1，and NF-κB p50 in diaphragm were measured by Western blot. The concentration of IL-17 in serum and diaphragm was measured by ELISA. Results Western blot showed that the protein expressions of E2-14K，MAFbx，MuRF-1，and NF-κB p50 in diaphragm increased significantly in the COPD model group compared with the normal control group （0.96±0.12 vs. 0.53±0.09，0.99±0.10 vs. 0.53±0.08，0.95±0.08 vs. 0.51±0.16，1.11±0.10 vs. 0.64±0.50，respectively，Plt;0.01）. The IL-17 level in serum and diaphragm was significantly higher in the COPD group than the control group. The expression of NF-κB p50 was positively correlated with E2-14K，MAFbx，and MuRF-1 expressions （r=0.82，0.92，0.86，respectively，Plt;0.01）. Both in serum and diaphragm，IL-17 level was positively correlated with the percentage of neutrophils，levels of NF-κB p50，E2-14K，MAFbx，and MuRF-1 expressions（all Plt;0.01）. The IL-17 levels in serum and diaphragm were also positively correlated each other （r=0.84，Plt;0.01）. Conclusions The results show that the ubiquitin-proteasom pathway，the NF-κB pathway and IL-17 are up-regulated in diaphragm of COPD rats .These alterations may contribute to diaphragm atrophy in COPD.
Objective To study the role of ubiquitin-proteasome pathway in diaphragm of COPD rats. Mathods Thirty rats were divided into a normal control group and a COPD group. COPD model was established by exposure to cigarette smoke for three months. The protein levels of E2-14k and proteasome subunit C8 in diaphragms were measured by Western blot. The mRNA levels of ubiquitin and proteasome subunit C2 in diaphragms were measured bymeans of realtime polymerase chain reaction( RT-PCR) . Results Compared with the control group, the protein expression of E2-14k increased significantly in the COPD group ( 0. 81 ±0. 28 vs 0. 50 ±0. 25, P lt;0. 05) , but C8 protein level was not significantly different between the two groups( P gt;0. 05) . The mRNA expression of ubiquitin increased significantly in the COPD group( 0. 89 ±0. 20 vs 0. 50 ±0. 15, P lt;0. 05) , but C2 mRNA level was not significantly different between the two groups ( P gt; 0. 05 ) . Conclusions The mRNA and protein expressions of ubiquitin-proteasome pathway in diaphragmincreased significantly in COPD rats, suggesting that the activity of ubiquitin-proteasome pathwayincreased, which lead to an increase of protein degradation.
ObjectiveTo explore the effects of volume mechanical ventilation with different tidal on the diaphragm discharge in rats. MethodsTwenty-four SD rats were randomly divided into three groups, namely a high tidal volume group, a low tidal volume group, and a control group. The rats in the high tidal volume group and the low tidal volume group underwent volume controlled ventilation with tidal volume of 10 mL/kg and 5 mL/kg, respectively. The rats in the control group breath spontaneously after anesthetization. The EMGdi frequency, diaphragm discharge area, product of diaphragm discharge amplitude and diaphragm discharge rate (A×R) were measured every 2 hours to analyze the characteristics of diaphragm of rats under different duration of ventilation. ResultsCompared with the control group, there was no statistical difference of A×R in the high tidal volume group, but the frequency of the diaphragm discharge reduced and the discharge diaphragm area increased. When compared the low tidal volume group with the control group, only the A×R increased significantly. The transcutaneous oxygen saturation (SpO2) and end-tidal CO2 pressure (PetCO2) in the high tidal volume group decreased significantly compared to the control group while the other indexes had no difference. ConclusionsThe effects of mechanical ventilation with different tidal volume on the rat diaphragm discharge are different. The low tidal volume mechanical ventilation can excite the respiratory center and strengthen the diaphragm discharge with the stabilization of physiological index while the high tide volume inhibits diaphragm function and damages the oxygenation.
ObjectiveTo evaluate clinical outcomes of diaphragm plication for the treatment of diaphragmatic paralysis (DP) in infants after surgical correction for congenital heart diseases. MethodsClinical data of 13 infants who had DP after surgical correction for congenital heart diseases from December 2009 to December 2012 were retrospectively analyzed. There were 5 male and 8 female patients with their age of 35 days-11 months (6.6±3.2 months) and body weight of 3.5-9.6 (6.2±1.8) kg. Diaphragm plication was performed 19.08±4.29 days after open heart surgery. All the patients were not able to wean from mechanical ventilation,or were repeatedly reintubated because of severe respiratory failure after extubation. All the 13 patients received diaphragm plication for singleor double-sided DP. ResultsTwo patients had ventilator associated pneumonia (15.4%) including 1 patient with positive sputum cultures for Acinetobacter baumannii but negative blood culture. Another patient who had double-sided DP after surgical correction for tetralogy of Fallot with pulmonary atresia underwent double-sided diaphragm plication and later died of multiple organ dysfunction syndrome,whose sputum and blood cultures were both positive for Pseudomonas aeruginosa on the 11th day after double-sided diaphragm plication. Chest X-ray of all the patients showed plicated diaphragm in normal position after diaphragm plication. The average time from diaphragm plication to extubation was 5.38±3.09 days. After diaphragm plication,arterial partial pressures of oxygen (PaO2) significantly increased (90.22±8.47 mm Hg vs. 80.69±6.72 mm Hg,P<0.05) and arterial partial pressures of carbon dioxide (PaCO2) significantly decreased (39.87±6.31 mm Hg vs. 56.38±7.19 mm Hg,P<0.05). Twelve patients were followed up for 24 months after discharge. During follow-up,1 patient who received double-sided diaphragm plication had 2 episodes of pneumonia within 6 months after discharge. Respiratory function of all the other patients was normal. All the patients were in NYHA class Ⅰ-Ⅱ. ConclusionDiaphragm plication is a safe,easy and effective treatment to increase survival rate and decrease the incidence of hospital-acquired infection for infants who have DP and are unable to wean from mechanical ventilation after surgical correction for congenital heart diseases.
Objective To investigate the protective effects of recombinant human insulin-like growth factor-1 ( rhIGF-1) on apoptosis of diaphragm in rats with COPD and its impact on pulmonary function. Methods Forty-five male Wistar rats were randomly divided into three groups, ie. a normal control group, a model group, and an IGF-1 intervention group, with 15 rats in each group. The rats in the model group and IGF-1 group were exposed to 5% smoke ( 30 min perday, lasting 28 days) in a sealed box, and 200 μg lipopolysaccharide was injected intratracheally on the 1st and 14th day. The rats in the IGF-1 group were given rhIGF-1 ( 60 μg /100 g) additionally by subcutaneous injection once a day, lasting 28 days. On the 1st, 14th, 28th day, 5 rats from each group were sacrificed. The weight, rate of apoptosis, Fas gene and Fas protein expression of isolated diaphragms were detected. The pulmonary function was measured on the 28th day before sacrificed. Results The mass of diaphragms, minute ventilation ( VE) , peak expiratory flow ( PEF) , inspiratory capacity ( IC) , forced expiratory volume in 0. 3 second ( FEV0. 3) of themodel groupand IGF-1 group were all decreased compared with the control group ( P lt; 0. 05) . The mass of diaphragms, VE, IC of the IGF-1 group were higher than those of the model group ( P lt;0. 05) , and the differences of PEF and FEV0. 3 were not significant ( P gt; 0. 05) . On the 14th, 28th day, rate of apoptosis, Fas gene and protein expressions in the IGF-1 group were lower than those in the model group, and still higher than those in the control group ( P lt; 0. 05) . Conclusions Fas/FasL mediated apoptosis way is involved in the diaphragm apoptosis. rhIGF-1 may reduce the apoptosis of the diaphragmand improve the VE and IC of rats with COPD by intervening Fas/FasL pathway.
ObjectiveTo evaluate the predictive value of the diaphragm ultrasound for weaning from mechanical ventilation.MethodsThe patients who received mechanical ventilation in Fujian Provincial Hospital between February 2016 to December 2017 and met the criteria for a T-tube spontaneous breathing trial were included in the study. Then right diaphragmatic displacement (DD) and diaphragmatic thickening fraction (DTF) were evaluated using M-mode ultrasonography as well as the rapid shallow breathing index (RSBI, the ratio of respiratory rate to tidal volume). A new index was named as the diaphragmatic-RSBI (D-RSBI, the ratio of respiratory rate to DD). The patients were classified into a success group or a failure group according to the weaning outcomes. The receiver operating characteristic (ROC) curves were calculated to evaluate the predictive performance of each index.ResultsFifty-nine patients were weaned successfully and failure of weaning was found in 29 patients. There were no statistically significant differences in pre-weaning parameters including age, sex, systolic blood pressure, diastolic blood pressure, blood lipid index (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride), or fast blood glucose between the weaning success group and the weaning failure group (P>0.05), but there were statistically significant differences in body mass index and acute physiology and chronic health condition Ⅱ score between two groups (P<0.05). DD [(13.44±3.23)mm vs. (10.28±2.82)mm, DTF [(32.43±12.35)% vs. (27.64±5.77)%, P<0.05] and D-RSBI [(1.49±0.47) breaths·min–1·mm–1 vs. (2.55±0.87) breaths·min–1·mm–1, P<0.05] differed significantly between the weaning success group and the weaning failure group. A cutoff of DTF≥27.9% yielded a sensitivity of 98.3%, a specificity of 62.1%, and an area under the ROC curve (AUC) of 0.873. A cutoff of D-RSBI≤1.73 breaths·min–1·mm–1 yielded a sensitivity of 76.3%, a specificity of 93.1%, and an AUC of 0.887. By comparison, when RSBI was ≤50.9 breaths·min–1·mm–1, there was a sensitivity of 91.5%, a specificity of 86.2%, and an AUC of 0.927. There was no statistically significant difference in AUC between D-RSBI and RSBI (P>0.05).ConclusionsDiaphragm ultrasound is feasible to predict the outcome of weaning. DTF and D-RSBI are as same accurate as the traditional RSBI in predicting the weaning outcome, but more objective and suitable for clinical application.
ObjectiveTo observe the curative effect of pulmonary rehabilitation in patients with stable moderate to severe chronic obstructive pulmonary disease (COPD).MethodsSixty-four patients with stable moderate to severe COPD who visited during January 2016 and December 2017 were recruited in the study. They were randomly divided into an observation group and a control group, with 32 cases in each group. The spirometry was conducted in all patients. The right deep inspiratory end diaphragm thickness and the quiet end expiratory diaphragm thickness were measured by ultrasound, and the diaphragm thickness fraction (DTF) was calculated. The routine drug treatment was given in both groups. The comprehensive pulmonary rehabilitation treatment was given in the observation group (include breath training, exercise training, health education and nutrition guide). The pulmonary function, diaphragm function, severity and quality of life were evaluated before and 6 months later after the treatment.ResultsIn the observation group, the predicted value of forced expiratory volume in one second (FEV1%pred), FEV1/FVC ratio and DTF were all significantly improved compare with before treatment and the control group (all P<0.05). While the BODE index was significantly declined compare with before treatment and the control group (all P<0.05).ConclusionPulmonary rehabilitation treatment can help improve pulmonary function, diaphragm function, condition of the disease and quality of life.
ObjectiveTo explore the effect of early graded respiratory severe rehabilitation training for patients with mechanical ventilation under a multidisciplinary model.MethodsTwo hundred and thirty-six patients were surveyed, who were hospitalized in the intensive care unit of the First Affiliated Hospital of Anhui Medical University from June 3, 2019 to March 31, 2020. They were randomly divided into an observation group and a control group, with 118 patients in each group. The observation group received rehabilitation training using early graded rehabilitation training under the mode of multidisciplinary cooperation, while the control group received routine respiratory rehabilitation training. Diaphragmatic excursion (DE) and diaphragmatic thickening fraction (DTF) of the patients before ventilator weaning were measured by ultrasound. The differences of DE, DTF, peak expiratory flow (PEF), maximal inspiratory pressure (MIP), success rate of withdrawal, duration of mechanical ventilation and intensive care unit (ICU) stay between the two groups were recorded and compared.ResultsAll evaluation indexes were statistically significant between the observation group and the control group (all P<0.05). There were interaction between oxygenation index, PEF, MIP, Acute Physiology and Chronic Health Score, Clinical Pulmonary Infection Score and recovery time.ConclusionRehabilitation training on early graded severe respiratory diseases under a multidisciplinary model can improve the respiratory function of patients on mechanical ventilation and shorten the duration of mechanical ventilation and ICU stay.
Objective To investigate the changes of respiratory mechanics in response to elevated respiratory central drive and their impacts on the inspiratory signals detection.Methods 10 normal volunteers were recruited for the study from the colleagues of the State Key Laboratory of Respiratory Disease. Rebreathing method was used to increase the end expiratory PCO2 ( PCO2 -ET) to the subject’s maximal tolerance in order to stimulate the increase of respiratory central drive. The changes of respiratory mechanics in response to elevated respiratory central drive and their impacts on the initiation signals of inspiration were observed.Results After re-breathing, the average maximal tolerated PCO2 -ET was ( 81. 2 ±6. 6) mm Hg. As the PCO2 -ET rising, electromyogram of diaphragmatic muscle ( RMSdi ) ,transdiaphragmatic pressure ( Pdi ) and tidal volume ( VT ) increased progressively while the time of respiratory cycle ( Ttot ) shorten gradually. As the PCO2 -ETlevel increased frombaseline [ PCO2 -ET( level-0) ] to the maximal level [ PCO2 -ET( level-4) ] , RMSdi increased from( 17. 17 ±12. 41) μV to ( 147. 99 ±161. 64) μV,Pdi and VT increased from ( 7. 5 ±1. 7) cmH2O and ( 0. 68 ±0. 27) L to ( 26. 13 ±11. 51) cm H2O and ( 2. 21 ±0. 37) L respectively, while Ttot shorten from ( 2. 91 ±0. 85) s to ( 1. 92 ±0. 39) s. These four parameters of respiratory mechanics, RMSdi, Pdi, VT and Ttot, were highly correlated linearly with PCO2 -ET ( r value was 0. 956, 0. 973,0. 956 and 0. 89 respectively, all P lt;0. 001) . At the start of inspiration, the first detectable signal was electromyogramof diaphragmatic muscle ( RMSdi) , followed by mouth pressure ( Pm)and inspiratory flow ( Flow) on time sequence. As the rising of PCO2 -ET, the time lag of Pmand Flow from RMSdi after the initiation of inspiration increased gradually. However, the time lag between Flow and Pm remained constant. Conclusions At the start of inspiration, the signal of RMSdi appears first as compared with Pm and Flow. As the rising of PCO2 -ET, the time lag of Pmand Flow fromRMSdi after the initiation of inspiration increased gradually, suggesting RMSdi is more sensitive inspiratory signal, which might be used for triggering of ventilator in order to improve the synchronization, especially in the situation of elevated respiratory central drive.
ObjectiveTwitch transdiaphragmatic pressure is used to evaluate the diaphragm function of mechanical ventilated chronic obstructive pulmonary disease patients before weaning in the intensive care unit, and compared with healthy normal values.MethodsPatients were recruited if they were with acute exacerbation of chronic obstructive pulmonary disease, admitted between May to November in 2013 and December 2014 to February 2016 to the intensive care unit in the First Affiliated Hospital of Guangzhou Medical University, intubated and mechanical ventilated more than 72 hours, and recovered to the clinical stability states after passing the readiness to wean, getting ready for spontaneous breathing test. The newly designed esophageal electrode catheter and bilateral anterolateral magnetic phrenic nerves stimulation were utilized to detect the twitch transdiaphragmatic pressure. At the same time, the function of diaphragm was detected in 10 healthy adults for comparison.ResultsTwenty-two patients were recruited in this study. Two cases had no twitch signals. In the rest 20 cases, the twitch transdiaphragmatic pressure was (7.6±2.5) cm H2O. In 10 healthy adults, twitch transdiaphragmatic pressure was (26.7±4.9) cm H2O. There was significant difference between the patients and the health control subjects (P<0.05).ConclusionTwitch transdiaphragmatic pressure is significantly decreased in weaning chronic obstructive pulmonary disease patients compared with healthy adults.