Correlation Analysis Between Opioids And Intraoperative Atrial Fibrillation And Its Protective Effect And Mechanism Of ARDS

Part ? Correlation analysis between opioids and atrial fibrillationAim The aim of this prospective observational study was to screen for risk factors of intraoperative atrial fibrillation(AF)during noncardiac thoracic surgery.Confirm whether opioids are associated with atrial fibrillation during surgery.Methods This study included 144 patients scheduled for thoracotomy under general anesthesia.We collected the patients' demographic and perioperative medical data in our hospital.AF was diagnosed using electrocardiography(ECG),on the basis of the presence of characteristic ECG features of AF by one or more ECG leads for at least 30 seconds.Results Of the participants,144 completed the study and 18 developed intraoperative AF.Higher percentages of subjects in the AF group than in the non-AF group had histories of chemotherapy(P=0.014)and alcohol consumption(P=0.034)before surgery.The AF group had a lower mean body mass index(P=0.019),significantly higher mean heart rate(P<0.001),and lower tidal volume(P=0.01)than the non-AF group.There was no correlation between opioid consumption and intraoperative atrial fibrillation.After the logistic regression analysis,only alcohol consumption(odds ratio[OR]=5.279;95%confidence interval[CI]:1.432-19.467),history of chemotherapy(OR=4.019;95%CI:1.504-15.334),and high heart rate(OR=1.093;95%CI:1.033-1.156)during one-lung ventilation were identified as the risk factors of AF during non-cardiac thoracic surgery.Conclusion The incidence of intraoperative AF during non-cardiac thoracic surgery was 12.5%.No correlation was found between opioids and intraoperative atrial fibrillation..Alcohol consumption,history of chemotherapy,and high heart rate during one-lung ventilation were the risk factors related to intraoperative AF.Part ? Protective effect and mechanism of opioid central preconditioning on acute respiratory distress syndromeAim To confirm whether morphine central preconditioning improve peripheral acute respiratory distress syndrome through opioid receptor mechanism.Methods:1:40 male Sprague-Dawley rats were randomly divided into two groups(n=20):LPS group(LPS 5 mg/kg,ip),LPS+morphine(icv)group(LPS 5 mg/kg,ip+Morphine 100 ug/kg,icv).The mortality of the SD rats in the two groups was observed within 72 hours after preconditioning of the lateral ventricle and administration of LPS.2:40 SD rats were grouped as above,the blood and bronchoalveolar larlavage fluid(BALF)were taken at 6 h,24 h,48 h and 72 h after LPS administration.ARDS-related inflammatory factors and protein quantification were performed.Taking the lung leaves for HE staining.3:30 SD rats were randomly divided into control group(Naive),LPS group(LPS 5 mg/kg,ip)and morphine high dose(icv)group(LPS 5 mg/kg,ip+mor 100 ug/kg,icv),morphine low dose(icv)group(LPS 5mg/kg,ip+mor 10 ug/kg,icv),naloxone antagonist group(LPS 5 mg/kg,ip+mor 100 ug/kg,icv+naloxone 1 mg/kg,iv),methylnaltrexone antagonist group(LPS 5 mg/kg,ip+mor 100 ug/kg,icv+methylnaltrexone 5 mg/kg,iv)six groups,5 per group.Lung tissue was taken 6 h after LPS administration,and the lung wet weight/dry weight ratio,HE staining,MPO and CD68 immunohistochemical staining were performed.Blood and BALF were used for inflammatory factor detection and arteriovenous blood was used for gas analysis.4:8 SD rats were cannulated tube in lateral ventricle and cut off the right neck vagus nerve for 7 days.They were randomly divided into the LPS(Vagotomy)group(Vagotomy+LPS 5 mg/kg,ip)and the morphine(icv)group(Vagotomy+LPS 5 mg/kg,ip+Mor 100 ug/kg,icv)4 per group.After 6 hours of LPS administration,lung tissue was taken for HE staining,MPO and CD68 immunohistochemical staining;blood and BALF were taken for inflammatory factor detection.5:6 SD rats were randomly divided into Vagotomy+PRV group(Cut off the right neck vagus nerve+PRV)and PRV group(normal control),with 3 rats in each group.Pseudorabies virus(PRV)was injected into the surface of the right lung.Brain slices were performed 2-4 days after injection to locate the central nucleus that direct control the lung.6:10 SD rats were cannulated tube in central nucleus and placed in a single cage and housed for 7 days.They were randomly divided into LPS group(LPS 5mg/kg,ip+0.9%NS 1 ul,nuclear injection),morphine nucleus administration group(LPS 5mg/kg,ip+MorlOug/lul,nuclear injection),and 5 rats in each group.Blood and BALF were used to measure the inflammatory factor IL-1?,and the brain nucleus?receptor and c-Fos immunofluorescence were co-labeled.Results:1:The mortality rate in the LPS group within 72 hours(42.9%)was significantly higher than that in the LPS+morphine(icv)group(10.5%)(P<0.05).Preadministration of morphine in lateral ventricle for three days can reduce the mortality induced by intraperitoneal injection of LPS.2:The levels of IL-1? and MCP-1 in plasma and BALF in LPS group were significantly higher than those in LPS+morphine(icv)group(P<0.05).The protein concentration in BALF of LPS group was significantly higher than that of LPS+morphine(icv)(P<0.05).HE staining showed that lung injury was the most serious at 24h and 48h.LPS +morphine(icv)group had significantly less lung tissue damage than LPS group.Preadministration of morphine in lateral ventricle can reduce the LPS-induced inflammatory response and shorten the course of ARDS.3:The percentage of MPO positive cells in LPS group and morphine small dose(icv)group was significantly higher than the Naive group and morphine high doses(icv)group(P<0.05).Compared with the Naive group,the PaO2/FIO2 in the LPS group and the naloxone antagonist group decreased significantly(P<0.05).The protein concentration in BALF of LPS group was significantly higher than that of Naive group and morphine high doses(icv)group(P<0.05).The concentration of IL-1? and MCP-1 in the BALF and blood of Naive group and morphine high dose(icv)group was significantly lower than that of LPS group(P<0.05).The effect of morphine on the improvement of ARDS was partially antagonized by opioid receptor antagonists.Preadministration of morphine in lateral ventricle to improve the ARDS is dose-related.The mechanism of morphine improves ARDS is associated with activation of central and peripheral opioid receptors.4:The concentration of MCP-1 in BALF of LPS(Vagotomy)group was significantly higher than that in morphine(icv)group(P<0.05).Other indicators were not statistically significant.The protective effect of morphine central pre-dosing on ARDS is dependent on the central-peripheral neuroimmunomodulatory pathway.5:There was no difference in the retrograde tracking of PRV virus from right lung surface between Vagotomy+ PRV group and PRV group(Normal control).It indicates that there are central nuclei that directly regulate the right lungs and not only rely on the right neck vagus nerve.6:The ?-receptor and c-Fos co-labeled in the morphine nucleus injection group are more than the LPS group.The average concentration of IL-1? in plasma and BALF of LPS group was higher than that of the morphine nucleus injection group,but the difference was not statistically significant.Pre-administration of the morphine lateral ventricle activates the central nucleus via the central ?-receptor.Conclusion:Preadministration of morphine in lateral ventricle can activates the central nucleus by activating the central opioid receptor mechanism,that lead to improve ARDS via the central-peripheral neuroimmune regulatory pathway.The protective effect is dose related.