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.
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.
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 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.
ObjectiveTo monitor the diaphragm function of mechanical ventilated patients in the intensive care unit. MethodsA prospective study was conducted on mechanical ventilation patients who had been evaluated by ventilation weaning screening test and planning to underwent spontaneous breathing trial between May 2013 and November 2013. A newly designed multi-function esophageal electrode was used to record the phrenic nerve conduction time (PNCT),diaphragm compound muscle action potential (CMAP) and twitch transdiaphragmatic pressure (TwPdi) elicited by bilateral anterolateral magnetic phrenic nerve stimulation. Results14 patients were recruited in this study. 1 case exited because of intolerance of repetitive magnetic stimulation,2 cases had no diaphragmatic electromyographic signals nor twitch signals,1 case had diaphragmatic electromyographic signal but could not be elicited by magnetic stimulation,1 case had no available TwPdi value with PNCT of 7.2 ms and CMAP of 1.26 mV. In the rest 9 cases,the PNCT,CMAP and TwPdi were (8.5±1.5)ms,(1.01±0.35)mV,(11.2±4.7)cm H2O,respectively. ConclusionNewly designed multi-function esophageal electrode catheter combined with bilateral anterolateral magnetic phrenic nerve stimulation can be used for non-volitional comprehensive assessment of diaphragm in critically ill patients,but not suitable for all subjects.
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.
ObjectiveTo investigate the clinical manifestations, diagnosis and treatment of diaphrammatic paralysis (DP) in infants with congenital heart disease (CHD) after cardiac surgery. MethodsBetween October 2008 and June 2014, among 2 962 infant patients ( < 1 year) underwent cardiac surgery for congenital heart disease, postoperative DP was diagnosed in 31 patients. The paralysed hemidiaphragm was left side in 10 patients, right side in 15 patients, and bilateral in 6 patients. There were 22 males and 9 females. The age at operation was 1-12 (4.5±4.2) months on the average. The body weight at operation was 2.9 to 8.5 (5.6±2.2) kg on the average.All children received mechanical ventilation. ResultsNo patient died in this study.There was a statistical difference between preoperative and postoperative mechanical ventilation time at 123-832 (420±223) hours versus 15-212 (75±58) hours (P < 0.05). ConclusionsDP caused by phrenic nerve injury during surgical intervention for congenital heart disease is an important risk factor in terms of morbidity during the postoperative period. Diaphragmatic plication appears a good option, especially in infant children, to wean patients from mechanical ventilation and to prevent long-term side effects of mechanical ventilation.
ObjectiveTo investigate the clinical features,treatment and pathogenesis of shrinking lung syndrome (SLS). MethodsA patient of systemic lupus erythematosus(SLE)with SLS as initial manifestation was reported.Literatures about SLS were comprehensively reviewed for its clinical characteristics and pathogenesis. ResultsA 27-year-old man was admitted with chief complaint of intermittent dyspnea and chest pain in 2009.Chest X-ray showed small lung volume and elevated diaphragms.Chest CT revealed bilateral pleural thickness and multiple atelectasis,without significant sign of interstitial fibrosis.Lung function showed restrictive pattern.Routine blood test revealed declined white blood cell and platelet count.C3 and C4 were declined.The autoantibody test revealed positive ANA,dsDNA,AHA,and RNP antibody.A diagnosis of SLE with SLS was made.The patient received corticosteroids and immunosuppressive therapy and was followed up for 5 years.His symptoms had relieved,but there was no obvious improvement in chest radiology and lung function.A total of 118 SLS cases were recorded in literature review,among which 100 were females and 18 were males.The average age was 32.98±14.66 years.Common clinical features of SLS included dyspnea,chest pain,orthopnea,breathlessness,and decreased breath sound.Radiology revealed small lung volume,elevated diaphragm,and dysfunction of diaphragm.Lung function showed restrictive pattern.The primary treatment of the disease was corticosteroid and immunosuppressive agents.The use of theophylline,β-agonist and rituximab was also reported. ConclusionWe should be aware of SLS in patients with SLE or other autoimmune diseases when they present with unexplained dyspnea.
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 investigate the relationship of diaphragmatic mobility (ΔM) evaluated by ultrasonography with quality of life and athletic ability in patients with chronic obstructive pulmonary disease (COPD) , and analyze the factors those affect the diaphragmatic mobility.MethodsA total of 48 male patients with stable COPD were recruited in the study. The body height, body weight, diaphragmatic mobility, airflow obstruction (FEV1%pred), and exercise capacity (6MWD) were measured. The quality of life was assessed using the St. George’s Respiratory Questionnaire (SGRQ).ResultsThe minimum value of ΔM was 1.89 cm and the maximal value was 8.11 cm in the COPD patients. There were significant correlationship between ΔM and the SGRQ score of the total score, symptom score, impact points, activity points and 6MWD, with correlation coefficients of –0.474, –0.416, –0.432, –0.502 and 0.536, respectively. Multivariate stepwise regression analysis showed that the factors influencing ΔM were height (β=0.407, P=0.021) and FEV1%pred (β=–0.391, P=0.035).ConclusionsDiaphragmatic mobility and quality of life are closely related in COPD patients. The height and FEV1%pred have the greatest effect on diaphragmatic activity. The smaller diaphragm mobility is relevant to the worse quality of life and the smaller activity capacity.