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

BACKGROUNDThe antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP).

METHODSA total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction.

RESULTSFour of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET).

CONCLUSIONSSepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.

Acetylcholinesterase ; metabolism ; Androstanols ; pharmacology ; Animals ; Cecum ; injuries ; Cholinesterase Inhibitors ; pharmacology ; Diaphragm ; drug effects ; metabolism ; Disease Models, Animal ; Ligation ; Male ; Neostigmine ; pharmacology ; Neuromuscular Junction ; enzymology ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Punctures ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sepsis ; physiopathology

OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on contraction capacity of diaphragm in type 1 diabetic rats.
 METHODS: Thirty-two male SD rats were randomly divided into a normal group (NC), a diabetic group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8). Intraperitoneal injection of streptozotocin was utilized to establish diabetic rat model. After the modeling, the rats in the DM+NaHS and the NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution. 8 weeks later, the diaphragm contractility was assessed by isolated draphragm strips perfusion. The peak twitch tension (Pt), maximum tetanic tension (Po) and maximal rates of contraction/relaxation (±dT/dtmax) were determined. The alterations in diaphragm ultrastructure were observed under electron microscopy. The diaphragm weight/body weight (DW/BW) was measured. The activities of succinic dehydrogenase (SDH), lactate dehydrogenase (LDH) and sarcoplasmic reticulum Ca2+ ATPase (SERCA) were analyzed by spectrophotometric method. The mRNA levels of SERCA and prospholamban (PLB) in diaphragm were detected by RT-PCR.
 RESULTS: Compared with the NC group, there was no significant change in all measured index in the NaHS group (P>0.05), while Pt, Po and ±dT/dtmax were significantly decreased in the DM group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the diaphragm. The DW/BW ratio and the activities of SDH, LDH and SERCA were decreased. The SERCA mRNA was decreased, while PLB mRNA was increased. Compared with the DM group, the diaphragm contractility and ultrastructure damage were improved in the DM+NaHS group. The DW/BW ratio and the activities of SDH, LDH and SERCA were increased. The SERCA mRNA was increased, while PLB mRNA was decreased (all P<0.05).
 CONCLUSION H(2)S can enhance the contraction capacity of diaphragm in type 1 diabetic rats, which is involved in regulating the activities of biological enzymes and the gene expressions of calcium regulatory proteins.
Animals ; Body Weight ; Diabetes Mellitus, Experimental ; physiopathology ; Diaphragm ; drug effects ; ultrastructure ; Hydrogen Sulfide ; pharmacology ; L-Lactate Dehydrogenase ; metabolism ; Male ; Muscle Contraction ; drug effects ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Succinate Dehydrogenase ; metabolism ; Sulfides ; pharmacology

OBJECTIVETo observe the anesthetic efficacy and safety of bilateral ultrasound-guided supraclavicular brachial plexus block in patients undergoing arthrolysis for shoulder periarthritis.

METHODSTwenty-seven patients (ASA class I-II) undergoing bilateral shoulder joint release surgery and 24 ml received bilateral ultrasound-guided supraclavicular brachial plexus block anesthesia with 0.4% ropivacaine and 0.8% lidocaine. The visual analogue scale (VAS) scores for shoulder joint pain were recorded before and after anesthesia. The efficacy of axillary nerve, dorsal scapular nerve and suprascapular nerve block was evaluated, and the anesthetic effect and complications was assessed during surgery. Before and after anesthesia, the range of left and right diaphragmatic muscle movement was measured when the patient took a quiet breath and a deep breath.

RESULTSThe patients showed no significant variations in MAP, HR, or SpO₂after anesthesia. The VAS scores of shoulder joint pain during anteflexion, abduction, posterior extension, rotation, posterior extension and medial rotation were significantly lowered after anesthesia (P<0.05), but the left and the right diaphragm movement range showed no significant difference between quiet breath and deep breath (P>0.05). The rates of complete block of the axillary nerve and dorsal scapular nerve was 100%, and that of suprascapular nerve was 92.6%. Partial phrenic nerve block occurred in 1 case with mild local anesthetic toxicity in another.

CONCLUSIONSBilateral ultrasound-guided supraclavicular brachial plexus block in patients has excellent analgesic effect in should joint release surgery with good safely.

Amides ; Anesthetics, Local ; Brachial Plexus Block ; Diaphragm ; Humans ; Lidocaine ; Orthopedic Procedures ; Pain Measurement ; Periarthritis ; diagnostic imaging ; surgery ; Shoulder Joint ; diagnostic imaging ; physiopathology ; Ultrasonography

OBJECTIVETo study the changes in diaphragmatic function and gene expressions of calcium regulatory proteins in diabetic rats and explore the mechanism of diaphragm dysfunction in diabetes mellitus.

METHODSSD rats were randomly divided into normal control group and diabetic (induced by intraperitoneal STZ injection) group. After 4 and 8 weeks, the body weight and diaphragm to body weight ratio were measured, and the activities of succinic dehydrogenase (SDH) in the diaphragm and blood glucose were assayed. The diaphragm contractility was assessed and the alterations of diaphragm ultrastructure were observed. RT-PCR was used to detect the changes in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) mRNA expressions in the diaphragm.

RESULTSThe diabetic rats showed a significant weight loss with a lowered diaphragm to body weight ratio (P<0.01) and SDH activity (P<0.01). The peak twitch tension and maximum tetanic tension of the diaphragm were significantly lowered and the time to peak contraction and half relaxation time significantly prolonged (P<0.01) in the diabetic rats, which also exhibited a lowered tetanic force in response to stimulus (P<0.01). Transmission electron microscopy revealed obvious ultrastructural changes of the diaphragm in diabetic rats. RT-PCR showed significantly decreased SERCA and increased PLB mRNA expressions in diabetic rat diaphragm (P<0.01), and these changes intensified with time (P<0.01).

CONCLUSIONDiabetes can cause impairment of diaphragmatic ultrastructure, mitochondrial injuries, and lowered SDH activity and ATP production. Decreased SERCA and increased PLB mRNA expressions in diabetes result in reduced Ca(2+) uptake by the diaphragm sarcoplasmic reticulum to induce diaphragm dysfunction.

Animals ; Body Weight ; Calcium ; metabolism ; Calcium-Binding Proteins ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; physiopathology ; Diaphragm ; metabolism ; physiopathology ; Glucose ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Succinate Dehydrogenase ; metabolism

OBJECTIVETo study the changes of inducible nitric oxide synthase (iNOS) activity and apoptosis-related genes Bcl-2, Bax and caspase-3 mRNA expressions in endotoxemia-induced rat diaphragm injury and analyze the related apoptosis mechanism.

METHODSThirty-two male SD rats were randomly divided into 4 groups (n = 8): control group (saline 0.5 ml ip), endotoxin 24 h, 48 h and 96 h group (endotoxin 12 mg/kg ip, animals were killed either 24, 48 or 96 h after injections). Body weight were measured, the ratio between diaphragm weight and body weight, activities of constitutive nitric oxide syntheses (cNOS), iNOS and succinate dehydrogenase (SDH) were also measured. The expressions of Bcl-2, Bax and caspase-3 mRNA were detected by RT-PCR analysis.

RESULTSEndotoxin induced significant reductions in diaphragm mass in endotoxin 96 h group (P < 0.05). Endotoxin increased diaphragm cNOS or iNOS activities, and they were significantly higher in endotoxin 96 h group than those in endotoxin 24 h and 48 h groups, diaphragm SDH activity was reduced, and it was lower in endotoxin 96 h group than that in endotoxin 24 h and 48 h groups (P < 0.01). Endotoxin significantly increased Bax and caspase-3 mRNA expressions, and they were higher in endotoxin 48 h and 96 h groups than those in endotoxin 24 h group (P < 0.01). Endotoxin significantly reduced Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, and they were lower in endotoxin 48 h and 96 h groups than those in endotoxin 24 h group (P < 0.01).

CONCLUSIONiNOS is activated in endotoxemia-induced rat diaphragm injury. It damages mitochondria, upregulates Bax expression and downregulates Bcl-2 expression, then induces caspase-3 related apoptotic pathway. These changes may cause diaphragm injury and atrophy.

Animals ; Apoptosis ; Caspase 3 ; metabolism ; Diaphragm ; metabolism ; physiopathology ; Endotoxemia ; metabolism ; Gene Expression ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the effects of Bufei Jianpi Recipe (BJR) on the diaphragmatic neural discharge and the diaphragmatic muscle function in rats with chronic obstructive pulmonary disease (COPD).

METHODSRats were randomly divided into the normal control group, the model group, the high dose BJR group (9.68 g/kg x d(-1)), the medium dose BJR group (4.84 g/kg x d(-1)), the low dose BJR group (2.42 g/kg x d(-1)), and the aminophylline group (2.3 mg/kg x d(-1)). The stable phase COPD rat model was prepared using repeated smoke inhalations and bacterial infections. The high, medium, and low dose BJR and aminophylline was respectively administered to rats from the ninth week to the twentieth week. The sampling was taken. The lung function, diaphragmatic neural discharge time (Td), and diaphragmatic neural discharge interval (Tdi), diaphragmatic neural discharge range (Rd), diaphragmatic neural discharge area (Ad), expiratory time (Tex), inspiratory time (Tin), respiratory rate (RR), respiratory excursion (RE), respiratory area (RA), and diaphragmatic muscular tension and endurance were detected.

RESULTSCompared with the normal control group, the tidal volume (TV), peak expiratory flow (PEF), and 50% tidal volume expiratory flow (EF50) significantly decreased in the model group (P < 0.01). Td, Tdi, Tex, and Tin were significantly prolonged (P < 0. 05, P < 0.01). Ad, Rd, RR, RE, RA, diaphragmatic muscular tension and endurance significantly decreased (P < 0.05, P < 0.01). The ratio of type I and IIA diaphragmatic fibers significantly increased and type IIB significantly decreased (P < 0.01). The activity of ATP decreased and the activity of SDH increased (P < 0.01). The aforesaid indices were improved to different degrees in BJR groups, especially in the high dose BJR group and the medium dose BJR group (P < 0.05, P < 0.01).

CONCLUSIONSBJR could significantly improve the diaphragmatic neural discharge and the diaphragmatic muscle function. Its efficacy was better than that of aminophylline.

Aminophylline ; pharmacology ; Animals ; Diaphragm ; drug effects ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Phrenic Nerve ; drug effects ; physiopathology ; Phytotherapy ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; physiopathology ; Rats

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

A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters. However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients. Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. There were significant negative correlations between diaphragmatic mobility and PaCO2 (r = -0.373, P = 0.030). Diaphragmatic mobility correlated with airway obstruction (FEV1, r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003). Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation. No relationship was observed between diaphragm mobility and PaO2 (r = -0.028, P = 0.873). These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients.
Aged ; Airway Resistance/physiology ; Carbon Dioxide/blood/physiology ; Diaphragm/physiopathology/*ultrasonography ; Female ; Humans ; Hypercapnia/complications/*physiopathology ; Male ; Middle Aged ; Portal Vein ; Pulmonary Disease, Chronic Obstructive/complications/*physiopathology/ultrasonography ; Pulmonary Gas Exchange ; Respiratory Muscles/physiopathology