ABSTRACT
OBJECTIVE：To investigate the effects of lidocaine aerosol inhalation on perioperative pulmonary function ， inflammation factor and related complications of patients with one-lung ventilation. METHODS ：A total of 120 patients who were admitted to the Affiliated Hospital of Panzhihua University from January 2018 to May 2020 and planned to undergo partial pneumonectomy under general anesthesia and one-lung ventilation were selected. According to random number table method ，they were divided into lidocaine aerosol inhalation group （group L ）and sterile water aerosol inhalation group （group N ），with 60 cases in each group. Two groups were given Midazolam injection 0.1 mg/kg+Propofol injectable emulsion 2.0 mg/kg+Sufentanil citrate injection 0.4 μg/kg to induce anesthesia. After the insertion of the double-lumen tracheal tube ，group L was given aerosol inhalation of Lidocaine hydrochloride injection 1.5 mg/kg diluted to 20 mL with sterile water ；group N was given aerosol inhalation of sterile water 20 mL at the flow rate of 2 L/min. Patients in both groups were continuously pumped with Propofol injectable emulsion 4-12 mg/（kg·h）+Remifentanil hydrochloride for injection 0.2-1 μg（/ kg·min）+Cisatracurium besilate for injection 0.05-0.1 mg/（kg·h）for anesthesia maintenance. Eight hours after operation ，group L inhaled of Lidocaine hydrochloride injection 1.5 mg/kg diluted to 20 mL with sterile water again ，and group N inhaled of sterile water 20 mL again. Arterial blood gas analysis indexes [arterial partial pressure of oxygen （PaO2），partial pressure of carbon dioxide （PaCO2），lactic acid （Lac），oxygenation index （P/F）]，serum inflammatory factors [interleukin 6 （IL-6），tumor necrosis factor α（TNF-α）and nuclear factor κB（NF-κB）] were observed in 2 groups before anesthesia（T1），60 min of one-lung ventilation （T2），and 12 h after extubation （T3）. Respiratory and circulatory parameters [extravascular lung water（EVLW），pulmonary vascular permeability index （PVPI），heart rate （HR），stroke volume （SV）] were also observed 5 min after anesthesia （t1），T2 and 15 min after surgery （t3）. Extubation time ，visual analogue scale （VAS） score of 12 h after extubation，time of getting out of bed ，the incidence of throat pain of 12 h after extubation and the occurrence of ADR were recorded in 2 groups. RESULTS ：There was no significant difference in arterial blood gas analysis indexes ，serum inflammatory factor levels ，respiratory and circulatory parameters between the two groups at T 1 or t 1（P＞0.05）. The levels of PaO 2，PaCO2， Lac，IL-6，TNF-α and NF-κB in 2 groups at T 2 and T 3 were significantly higher than at T 1，P/F at T 2 and T 3 was significantly lower than at T 1；in group L ，the levels of PaCO 2，Lac，IL-6，TNF-α，NF-κB were significantly lower than group N，and PaO 2 and P/F were significantly higher than group N （P＜0.05）. EVLW and PVPI of 2 groups at T 2and t 3，SV of group L ，HR of group N were significantly higher than corresponding group at T 1，while EVLW ，PVPI and HR of group L were significantly lower than group N，SV was significantly higher than group N at corresponding period （P＜0.05）. The extubation time ，VAS score of 12 h after extubation，time to get out of bed after surgery ，the incidence of throat pain of 12 h after extubation in group L were significantly shorter or lower than group N （P＜0.05）. No obvious and serious ADR occurred during recovery. CONCLUSIONS：Lidocaine aerosol inhalation can effectively improve ventilation and oxygenation function of patients undergoing one-lung ventilation ，inhibit the release of inflammatory factors ，and reduce the incidence of postoperative complications with good safety.
ABSTRACT
Objective To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac 1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism.Methods Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group,normal tidal volume (VT) group and high VT group with 10 rats in each group.The rats in spontaneous respiration group were kept their spontaneous breathing.The rats in normal VT group and high VT group were performed tracheal intubation after tracheostomy,and underwent mechanical ventilation on bilateral lungs with 6 mL/kg and 40 mL/kg VT respectively with maintenance anesthesia.After 4-hour ventilation,heart blood,bronchoalveolar lavage fluid (BALF) and lung tissues were harvested.The levels of interleukins (IL-1β,IL-6),tumor necrosis factor-α (TNF-α),myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA).Lung wet/dry radio (W/D) was determined.The lung tissues were stained with hematoxylin and eosin (HE),and pathological changes were observed,and pathological scores were evaluated.The ultra structure changes in type Ⅱ alveolar epithelial cells (AEC Ⅱ)were observed with transmission electron microscope.The positive expressions of phosphorylation of extracellular signal-regulated kinase (p-ERK) were determined by immunohistochemistry,and those of Racl and F-actin were determined by immunofluorescence.The mRNA expressions of ERK and Rac1 were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR),and protein expressions of Rac-1,p-ERK and F-actin were determined by Western Blot.Results ① Compared with spontaneous breathing group,lung W/D in both mechanical ventilation groups was significantly increased,with more significant increase in the high VT group (6.64 ± 0.88 vs.1.79 ± 0.36,P ＜ 0.01).② There was no obvious pathological changes in the lung tissue and AEC Ⅱ of the spontaneously breathing group.In the normal VT group,there was slight edema and infiltration of inflammatory cells;AEC Ⅱ had less lamellar bodies and uniform distribution of the villi of the alveolar epithelium.In the high VT group,the edema of the lung tissue,the widening of the pulmonary septum,the alveolus congestion,the infiltration of inflammatory cells,and alveolar structure disorder were found;and AEC Ⅱ was irregular,the number of lamellar bodies in the plastids was decreased and was unevenly distributed.The pulmonary histopathological score in the high VT group was significantly higher than that in the spontaneous breathing group and the normal VT group (12.00 ± 2.00 vs.6.00 ± 1.51,8.50 ± 0.53,both P ＜ 0.01).③ Compared with spontaneous breathing group,IL-1β,IL-6,TNF-α,MPO,and MIP-2in serum and BALF in both mechanical ventilation groups were significantly increased,with more siguificant increase in the high VT group [serum IL-1 β (ng/L):104.2 ± 15.1 vs.20.3 ± 8.3,IL-6 (ng/L):46.6 ± 11.5 vs.22.7 ± 7.5,TNF-α (ng/L):39.4±6.5 vs.5.4± 1.9,MPO (ng/L):0.66±0.24 vs.0.06±0.03,MIP-2 (ng/L):109.2±25.8 vs.22.8±8.4;BALF IL-1 β (ng/L):121.5 ± 25.6 vs.24.0 ± 7.5,IL-6 (ng/L):136.7 ± 32.7 vs.31.4 ± 10.5,TNF-α (ng/L):98.0 ± 14.8vs.10.1 ±2.6,MPO (ng/L):0.80±0.31 vs.0.08±0.04,MIP-2 (ng/L):144.4±28.9 vs.41.2±20.7;all P ＜ 0.01].④ There were only a few p-ERK,Rac1 and F-actin positive expressions in the spontaneous breathing group.The positive expressions in normal VT group were increased.In high VT group,the positive expression of p-ERK was significantly increased;Rac1 and F-actin were mainly distributed in the cell membrane and cytoplasm respectively,the positive expressions were further enhanced.⑤ The gene expressions of ERK and Rac1,and protein expressions of p-ERK,Rac1 and F-actin in the high VT group were significantly higher than those in the spontaneous breathing group and normal VT group [ERK mRNA (2-△△Ct):8.23±2.83 vs.1,3.02± 1.38,p-ERK protein (gray value):1.15±0.36 vs.0.61 ±0.23,0.88±0.22;Rac1 mRNA (2-△△Ct):4.45 ±2.26 vs.1,1.22±0.39,Rac1 protein (gray value):0.91 ±0.16 vs.0.48±0.11,0.55 ± 0.10;F-actin protein (gray value):0.70± 0.09 vs.0.49 ± 0.08,0.55 ± 0.04;all P ＜ 0.01].Conclusion F-actin expression in lung tissue was up-regulated in rats with VILI,which resulted in reconstruction of AEC Ⅱ cyto-skeleton,and variation of cell membrane permeability through Rac 1 /MAPK/ERK sigualing pathway during VILI.
ABSTRACT
OBJECTIVE:To observe the effects of dexmedetomidine combined with ulinastatin on stress reaction indexes,ex-travascular lung water value(EVLW)and pulmonary vascular permeability indexes(PVPI)and other parameters in one-lung venti-lation(OLV)lobectomy patients. METHODS:A total of 80 patients underwent OLV lobectomy selected from the Affiliated Hospi-tal of Southwest Medical University during Nov. 2015-Nov. 2016 were divided into control group (group N),ulinastatin pretreat-ment group(group U),dexmedetomidine continuous pump group(group D),ulinastatin pretreatment+dexmedetomidine continu-ous pump group(group U+D),with 20 cases in each group. Thirty min before anesthesia induction,all patients were given atro-pine sulfate 0.5 mg intramuscularly and received catheterization of right internal jugular vein and ipsilateral femoral artery under lo-cal anesthesia. Based on that,group N was given 0.9％ Sodium chloride injection 100 mL intravenously;group U was given sodi-um chloride mixed solution 100 mL containing Ulinastatin for injection 200000 U intravenously;group D was given continuous in-travenous pump of Dexmedetomidine hydrochloride injection 2 μg/mL mixed with sodium chloride mixed solution at 1 μg/(kg·h), and after induction intravenous pump at 0.5 μg/(kg·h)until the end of surgery;group U+D was given Sodium chloride mixed so-lution containing 200000 U ulinastatin 50 mL and 4 μg/mL dexmedetomidine sodium chloride mixed solution 50 mL intravenously (same dose as above during induction period and maintenance period). The levels of blood glucose,partial pressure of oxy-gen [p(O2)],adrenocorticotropic hormone (ACTH),norepi-nephrine (NE),heart rate (HR),cardiac output (CO),sys-temic vascular resistance(SVR),EVLW and PVPI were com-pared among 4 groups 30 min before anesthesia induction(T1),2 h after the beginning of surgery(T2),immediately after extuba-tion(T3)and 12 h after surgery(T4). Liquid intake and output volume were recorded during T2-T4. The occurrence of ADR among 4 groups was observed. RESULTS:There was no statistical significance in each index among 4 groups at T1 (P>0.05). During T2-T4,the levels of blood glucose,ACTH,NE,SVR,EVLW and PVPI in group N were significantly higher than other 3 groups, and group U and D were significantly higher than group U+D,with statistical significance(P<0.05);there was no statistical sig-nificance between U and D(P>0.05). The levels of p(O2)and CO in groups U+D were significantly higher than other 3 groups, with statistical significance (P<0.05);there was no statistical significance among other 3 groups (P>0.05). HR of group N and U were significantly higher than other 2 groups,with statistical significance (P<0.05). There was no statistical significance be-tween group N and U,between group D and U+D(P>0.05). There was no statistical significance in liquid intake or output vol-ume among 4 groups (P>0.05). No obvious ADR was found in 4 groups. CONCLUSIONS:Dexmedetomidine combined with ulinastatin can significantly relieve stress reaction,and reduce the levels of part blood flow and respiratory dynamics indexes as EV-LW,PVPI in patients with OLV lobectomy so as to play lung protective effect.