OBJECTIVETo investigate the cardioprotective effects of morphine on ischemic reperfused rat heart in vitro and its mechanism.

METHODSThe isolated rat heart was perfused in a Langendorff apparatus. Infarct myocardium was determined by TTC. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), the first derivative of ventricular pressure (LVP/dtmax) and infarct size after ischemia and reperfusion in rat heart given 0.3 micro mol/L morphine were observed. The effects of naloxone and glibenclamide on the cardioprotection of morphine were also measured.

RESULTSAfter ischemia and reperfusion, CF, HR, LVP and LVP/dtmax of isolated rat hearts decreased significantly (P < 0.01). After morphine preconditioning, HR, LVP and LVP/dtmax increased (P < 0.01) and infarct size was reduced significantly (P < 0.01), while no significant change in CF (P > 0.05). The cardioprotective effects of morphine were abolished by naloxone or glibenclamide completely.

CONCLUSIONSMorphine can reduce ischemia-reperfusion injuries in isolated rat heart. The cardioprotective effects of morphine are mediated by a local opioid receptor-K(ATP) channel linked mechanism in rat hearts.

Animals ; Cardiotonic Agents ; pharmacology ; Glyburide ; pharmacology ; Heart ; drug effects ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; Male ; Morphine ; pharmacology ; Myocardial Reperfusion Injury ; prevention & control ; Naloxone ; pharmacology ; Rats ; Rats, Wistar

Objective To evaluate the effects of sevoflurane on hippocampal neurogenesis in den-tate gyrus (DG) of mice of different ages. Methods Ninety-six SPF healthy male C57BL∕6 mice, aged 2 weeks, 6 weeks, 9 months and 20 months (24 mice for each age, 12 mice for each group), were divided into 2 groups (n＝48 each) using a random number table method: control group (group C) and sevoflurane group (group S). Group S inhaled 3. 0% sevoflurane for 2 h once a day for 3 consecutive days, while group C inhaled the mixture of air and O2. Six mice of each age were selected, and 5′-bromo-2′-deoxyuridine (BrdU) 50 mg∕kg was intraperitoneally injected immediately before and after inhalation once a day for 3 consecutive days in two groups. Mice were sacrificed at 24 h after the last inhalation (T1), brains were re-moved and hippocampi isolated for determination of the number of nestin and doublecortin ( DCX) positive cells in DG by immunohistochemistry. Mice were sacrificed at 4 weeks after the last inhalation ( T2), brains were removed and hippocampi isolated for determination of the number of neuronal nuclei antigen (NeuN)∕BrdU and glial fibrillary acid protein ( GFAP )∕BrdU positive cells by immunofluorescence. Re-sults Compared with group C, the number of nestin and DCX positive cells was significantly reduced at T1, and the number of NeuN∕BrdU and GFAP∕BrdU positive cells was reduced at T2in mice of 2 weeks and 20 months old (P＜0. 05), and no significant change was found in the indices mentioned above in mice of 6 weeks and 9 months old in group S ( P＞0. 05). Conclusion Three percent sevoflurane can inhibit hipp-ocampal neurogenesis in DG of immature and old mice and exerts no influence on hippocampal neurogenesis in DG of juvenile and adult mice.

Objective To evaluate the effect of sevoflurane on activities of Na+-K+-ATPase and Ca2+-ATPase in the hippocampus of diabetic rats.Methods SPF healthy male Wistar rats,aged 8 weeks,weighing 180-200 g,were fed a high-fat diet for 3 consecutive weeks and streptozotocin was intraperitoneal-ly injected to induce type 2 diabetes mellitus.Forty-four rats with diabetes mellitus were divided into 2 groups (n=22 each) using a random number table:diabetic group (D group) and sevoflurane group (S group).Another 22 healthy Wistar rats,aged 8 weeks,weighing 180-200 g,served as control group (C group).Oxygen was inhaled for 2 h in C and D groups,and 2.4％ sevoflurane was inhaled for 2 h in S group.Eight rats were sacrificed at 30 min after treatment,brains were removed and hippocampi were isolated for measurement of Na+-K+-ATPase and Ca2+-ATPase activities in hippocampal tissues by spectrophotometry.Ten rats were randomly selected at 1 day after treatment,and Morris water maze test was performed to assess the cognitive function.Four rats were randomly sacrificed,brains were removed and hippocampi were isolated for examination of the mitochondrial ultrastructure with a transmission electron microscope.Results Compared with group C,the escape latency was significantly prolonged,the number of crossing the original platform was reduced,the percentage of time of staying at the original platform quadrant was decreased,the activities of Na+-K+-ATPase and Ca2+-ATPase in hippocampi were decreased (P＜ 0.05),and mitochondrial swelling and decreased mitochondrial cristae were observed under the electron microscope in group D.Compared with group D,the escape latency was significantly prolonged,the number of crossing the original platform was reduced,the percentage of time of staying at the original platform quadrant was decreased,the activities of Na+-K+-ATPase and Ca2+-ATPase in hippocampi were decreased (P＜ 0.05),and mitochondrial swelling and vacuolization were found under the electron microscope in group S.Conclusion The mechanism by which sevoflurane aggravates cognitive dysfunction is related to deceasing activities of Na+-K+-ATPase and Ca2+-ATPase in the hippocampus of diabetic rats.

Objective To evaluate the role of autophagy in cognitive decline caused by sevoflurane anesthesia and the relationship with neurogenesis in aged mice.Methods Forty-five healthy SPF male mice,aged 20-22 months,weighing 25-35 g,were divided into 3 groups (n=15 each) using a random number table method:control group (group C),sevoflurane anesthesia group (group S) and autophagy agonist rapamycin group (group R).Rapamycin 0.2 mg/kg was intraperitoneally injected every day for 7 days in group R,while the equal volume of solvent dimethyl sulfoxide was given instead in S and C groups.In group S and group R,3％ sevoflurane was inhaled for 2 h once a day for 3 consecutive days starting from 5th day of administration,while the mixture of air and oxygen was inhaled instead in group C.Five mice in each group were randomly selected after the last anaesthesia and sacrificed,and the hippocampus was removed for determination of the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and Beclin-1 by Western blot.The other mice were sacrificed after Morris water maze test was performed,and hippocampi were isolated for determination of doublecortin (DCX) positive cells in the dentate gyrus by immunohistochemistry.Results Compared with group C,the escape latency was significantly prolonged,the percentage of time spent in the target quadrant was decreased,the expression of LC3 Ⅱ and Beclin-1 was down-regulated,LC3 Ⅱ/LC3 Ⅰ ratio was decreased,and DCX positive cell counts were reduced in S and R groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the percentage of time spent in the target quadrant was increased,the expression of LC3 Ⅱ and Beclin-1 was up-regulated,LC3Ⅱ/LC3 Ⅰ ratio was increased,and DCX positive cell counts were increased in group R (P＜0.05).Conclusion Autophagy is involved in the process of cognitive decline caused by sevoflurane anesthesia,which is related to inhibiting neurogenesis in the hippocampus of aged mice.

Objective:To evaluate the effect of nicotinamide mononucleotide (NMN) on neurogenesis decline in sleep-deprived infancy rats.Methods:Seventy-eight clean-grade healthy male Sprague-Dawley rats, aged 7 days, weighing 10-15 g, were divided into 3 groups ( n=26 each) using a random number table method: control group (group Con), sleep deprivation group (group SD) and sleep deprivation plus NMN group (group SD+ NMN). Sleep deprivation model was established by gentle stimulation method with a brush (10 h per day) for 14 consecutive days.NMN 500 mg/kg was intraperitoneally injected in group SD+ NMN, while the equal volume of aqua pura was given instead in Con and SD groups.5′-bromo-2′-deoxyuridine (BrdU) 100 mg/kg was intraperitoneally injected immediately after the end of sleep deprivation to label the new-born cells.At 24 h after completion of sleep deprivation, the stem cell pluripotency transcription factor (SOX2) and doublecortin (DCX) positive cells in the hippocampal DG region were counted using immunofluorescence and immunohistochemical methods, and positron emission tomography-computed tomography was used to observe the metabolism of 18F-fluorodeoxyglucose in the hippocampus.At 4 weeks after completion of sleep deprivation, the number of neuronal nuclei antigen (NeuN)/BrdU and glial fibrillary acid protein (GFAP)/BrdU positive cells in hippocampal DG region was recorded using immunofluorescence, and novel object recognition test was performed to evaluate the cognitive function. Results:Compared with group Con, the number of SOX2 and DCX positive cells was significantly reduced, the standard uptake value of glucose in the hippocampus was decreased, the number of NeuN/BrdU and GFAP/BrdU positive cells was reduced, and discrimination index in novel object recognition test was decreased in group SD ( P<0.05). Compared with group SD, the number of SOX2, DCX NeuN/BrdU and GFAP/BrdU positive cells was increased, the standard uptake value of glucose in the hippocampus was increased, and discrimination index in novel object recognition test was increased in group SD+ NMN ( P<0.05). Conclusion:Nicotinamide mononucleotide can promote neurogenesis, thus improving cognitive function, and the mechanism is related to increasing the metabolism of hippocampal glucose in sleep-deprived infancy rats.

Objective:To compare the effects of desflurane and sevoflurane anesthesia on the sleep quality of sleep-deprived mice.Methods:Thirty-two clean-grade healthy male C57BL/6 mice, aged 10 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) by the random number table method: control group (C group), sleep deprivation group (SD group), sleep deprivation+ sevoflurane group (SD+ SEV group), and sleep deprivation+ desflurane group (SD+ DES group). In the four groups, EEG-EMG electrodes were implanted for recording EEG and EMG, and sleep deprivation model was developed by the gentle stimulation method with a brush for 12 h (6: 00-18: 00) after 7 days of adaptation. The 6 h after sleep deprivation was divided into 2 time periods: T 1 period (18: 00-20: 00) and T 2 period (20: 00-24: 00). T 1 period In SD group, mice were allowed ad libitum recovery sleep after sleep deprivation. C group and SD group were exposed to 60% oxygen 1.5 L/min. In SD+ DES group and SD+ SEV group, mice were exposed to 6% desflurane and 2.5% sevoflurane, respectively, for 2 h in 60% oxygen 1.5 L/min following sleep deprivation. T 2 period Four groups were allowed ad libitum recovery sleep with the EEG-EMG signal recording. The percentages and number of wakefulness time, rapid eye movement time and non-rapid eye movement time during each time period were calculated using Lunion Data software. Results:Compared with C group, the percentage of non-rapid eye movement time and the percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased during 12 h sleep deprivation in SD group, SD+ SEV group and SD+ DES group ( P<0.05). Compared with T 1 period, the percentage of non-rapid eye movement time was significantly increased, and the percentage of wakefulness time and percentage of rapid eye movement time were decreased in T 2 period in SD group ( P<0.05). Compared with SD group, the percentage of non-rapid eye movement time and percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased in T 2 period in SD+ SEV group and SD+ DES group ( P<0.05). There was no significant difference in the percentage of non-rapid eye movement, rapid eye movement and wakefulness time in T 2 period between SD+ SEV group and SD+ DES group ( P>0.05). Compared with SD+ SEV group, the number of non-rapid eye movement in T 2 period was significantly reduced in SD+ DES group ( P<0.05). Conclusions:The effect of desflurane anesthesia in improving sleep quality is better than sevoflurane anesthesia in sleep-deprived mice.

Objective To evaluate the effects of sevoflurane on neurogenesis in hippocampal den-tate gyrus(DG)of mice with Alzheimer′s disease. Methods Thirty-six SPF male APP∕PS1 mice, aged 8 months, weighing 30-35 g, were divided into 3 groups(n=12 each)using a random number table:Alzheimer′s disease group(group AD), oxygen group(group O2)and sevoflurane group(group Sev). Another 12 wild-type mice served as control group(group C). In group Sev, 30% sevoflurane was in-haled for 2 h once a day for 3 consecutive days. The mixture of air and oxygen was inhaled in group O2. Morris water maze test was performed on 22 to 28 days after the last sevoflurane inhalation. Then the mice were sacrificed and hippocampi were isolated for determination of doublecortin(DCX)positive cell count (by immunohistochemistry)and neuronal nuclei(NeuN)∕5-bromo-2′-deoxyuridine(BrdU)and glial fi-brillary acidic protein(GFAP)∕BrdU positive cell count in hippocampal DG(by immunofluorescence). Results Compared with group C, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, and DCX, NeuN∕BrdU and GFAP∕BrdU positive cell counts were reduced in AD, O2and Sev groups(P<005). There was no significant difference in each parameter between group O2and group AD(P>005). Compared with group O2, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, and DCX, NeuN∕BrdU and GFAP∕BrdU positive cell counts were reduced in group Sev(P<005). Conclusion Sevoflurane leads to cognitive decline through depressing neurogenesis in hippocampal DG of mice with Alzheimer′s disease.

Objective To summarize the experience of perioperative treatment of lung transplantation for end-stage lung disease. Methods Perioperative clinical data of 7 recipients undergoing lung transplantation were retrospectively analyzed, including 3 cases with bilateral lung transplantation and 4 cases with unilateral lung transplantation. The perioperative status and clinical prognosis of lung transplantation recipients were observed. Results The operation time of 7 lung transplantation recipients was (344±133) min. Cold ischemia time was (236±74) min in 4 cases of single-lung transplantation and (480±120) min in 3 cases of bilateral-lung transplantation. The length of Intensive care unit(ICU) stay was 21 (13-25) d and the length of hospital stay was 101 (64-117) d. In the first 3 d after surgery, the daily fluid output was significantly larger than the fluid input (all P < 0.05). The arterial oxygen partial pressure (PaO₂) of lung transplantation recipients in the first 3 d after surgery was significantly elevated than preoperative level (all P < 0.05), whereas the arterial carbon dioxide pressure (PaCO₂) did not significantly change (all P > 0.05). All recipients had pulmonary bacterial infection after lung transplantation, including 3 cases complicated with fungal infection. One recipient underwent exploratory thoracotomy for hemostasis due to active thoracic bleeding after operation, 1 recipient suffered from primary graft dysfunction (PGD) and 4 recipients received secondary endotracheal intubation. Two cases died after operation, 1 case died of septicemia caused by multidrug-resistant acinetobacter baumannii, the other case died of rejection reaction after self-terminating use of immunosuppressive agents. The remaining 5 cases were successfully discharged and recovered well. The longest survival period was 3.1 years. Conclusions In the perioperative management of lung transplantation, it has great significance to hold the surgical indications, monitor and manage postoperative refined fluid and hemodynamics, implement the strategy of protective pulmonary ventilation, and early diagnose and treat severe postoperative complications for the recipients of lung transplantation to safety through the perioperative period.

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.

BACKGROUND: Patients with pulmonary nodules are treated by minimally invasive surgery, and postoperative symptoms have become the main factors affecting patients' emotion and quality of life. This study aimed to analyze the changes of postoperative symptoms in lung cancer patients with pulmonary nodules. METHODS: The clinical data of eighty-eight lung cancer patients admitted to the same medical group of Department of Thoracic Surgery, West China Hospital of Sichuan University from June 2021 to September 2021 were prospectively collected and analyzed. The types and severity of clinical symptoms before operation, on discharge day, 30-day and 90-day after operation were analyzed. RESULTS: The incidence of postoperative symptoms in lung cancer patients was 79.5%, and most patients suffered from mild (54.3%) and moderate (32.9%) symptoms. The main postoperative symptoms of lung cancer patients were pain (55.7%) and cough (37.2%). The incidence of pain at discharge (55.7%) was significantly higher than that at 30-day (23.7%, P=0.01) and 90-day (12.0%, P=0.01) after discharge. The incidence of cough was significantly higher at 30-day (66.1%) and 90-day (66.0%) than that at discharge (37.2%) (P=0.01, P=0.04). CONCLUSIONS The main postoperative symptoms of lung cancer patients with pulmonary nodules are pain and cough. The incidence and severity of pain decreases with time, and the incidence of cough increases but the severity decreased gradually.
Cough/etiology* ; Humans ; Lung Neoplasms/surgery* ; Pain/etiology* ; Pneumonectomy/adverse effects* ; Quality of Life ; Thoracic Surgery, Video-Assisted/adverse effects*