| Part I:The lung protective effects of dexmedetomidine on one lung ventilation under low Fi02 ventilation mode in rabbits and investigation of its mechanismObjective:To observe the effects of dexmedetomidine on inflammatory response and lung injury induced by OLV under low FiO2 ventilation mode in rabbits,and to investigate its mechanism.Methods:Forty healthy New Zealand white rabbits were randomly divided into 4 groups(n=10 in each group):two lung ventilation(TLV)group(group T),OLV group(group O),dexmedetomidine OLV group(group D),dexmedetomidine combined with low FiO2 OLV group(group D-L).The rabbits were anesthetized with intravenous urethane 1 g/kg,then tracheostomized and inserted a ID 3.0 mm trachea tube for mechanical ventilation(respirator settings during TLV:VT=10ml/kg,FiO2=0.6,RR = 40 times/min,I:E = 1:2).The rabbits in group T were received TLV for 3.5 hours,After 30 minutes TLV,the rabbits in group O,group D,and group D-L were followed by right lung ventilation for 3 hours,the respirator settings during OLV in group O and group D were as same as that in group T except that FiO2=1.0,the respirator settings during OLV in group D-L were as same as that in group T.In group D and group D-L,dexmedetomidine were given intravenously at 1μg/kg over 10 minutes before tracheostomy,followed by intravenous infusion at the rate of 1μg/kg.h.Equal volume of normal saline were received in group O and group T.Observation indexes:(1)Arterial blood samples at TLV 30 min(T0),OLV 10 min(Ti),OLV 30 min(T2),OLV 60 min(T3),OLV 120 min(T4)and OLV 180 min(T5)were taken for blood gas analysis and oxygenation index were calculated.(2)At the end of the experiment,rabbits were sacrificed and lung tissues were collected,the pulmonary wet/dry weight(W/D)ratio was calculated and(3)pathological changes of the lung were examined by HE stain.(4)The level of tumor necrosis factor-a(TNF-a),interleukin-6(IL-6),high mobility group protein B1(HMGB1)contents were measured by ELISA.(5)The expressions of TLR4,NF-κB p65,ICAM-1 mRNA were analyzed by quantitative real-time PCR.(6)The expressions of NF-κB p65 protein were detected by western blot.Results:(1)Compared with group D,OI at Ti-T3 in group D-L was significantly increased(P<0.05or P<0.01).(2)Pulmonary W/D ratio of both sides of lung in group O,group D and group D-L was significantly higher as compared with group T.However,pulmonary W/D ratio in group D and group D-L was obviously lower than that in group O.(3)Rabbits in group T showed nearly normal lung histology,but rabbits in group O showed extensive morphological damage in the lung with a large amount of neutrophil and lymphocyte infiltratration,alveolar wall thickening.Morphological damage was relatively attenuated in group D and group D-L.Morphological damage in group D-L was more slighter than that of in group D.(4)Compared with group T,the level of TNF-α,IL-6 in Group O and group D were significantly increased(P<0.01).Compared with group O,the contents of TNF-a,IL-6 in group D and group D-L were obviously decreased(P<0.05or P<0.01).The contents of TNF-a,IL-6 in group D-L were further decreased as compared with group D(P<0.05or P<0.01).(5)The expressions of TLR4,NF-κBp65,ICAM-1 mRNA were increased significantly at 3 h in OLV in group O and group D as compared with group T(P<0.05or P<0.01),Compared with group O,the expressions of TLR4,NF-KBp65,ICAM-1 mRNA in group D and group D-L were significantly decreased(P<0.05or P<0.01),such enhancement being further ameliorated as observed in group D-L as compared with group D(P<0.05).(6)Compared with group T,the expressions of NF-κBp65 protein was increased significantly at 3 h in OLV in group O and group D(P<0.05orP<0.01),Compared with group O,the expressions of NF-κBp65 protein in group D-L was significantly decreased(P<0.05or P<0.01).Conclusions:Dexmedetomidine might inhibit the secretion of TNF-α,IL-6 and ICAM-1,thus attenuate OLV induced lung injury in rabbits,possibly by down regulation the expression of TLR4,NF-κB p65 mRNA and protein.Dexmedetomidine may exert synergistic effects under low FiO2 ventilation mode and thus further ameliorate the lung injury induced by OLV.Part II:Protective effects of dexmedetomidine on the lungs in patients undergoing thoracic surgery under conventional ventilation modeObjective:To observe the effects of dexmedetomidine on respiratory mechanics,oxygenation,inflammatory response,oxidative stress and postoperative pulmonary complications in patients with lung cancer undergoing conventional one lung ventilation mode.Methods:40 ASA Ⅰ or Ⅱ patients aged 40~64 yr,BMI 20～25 scheduled for thoracoscopic lobectomy were randomly divided into 2 groups(n=20 each):conventional ventilation group(group O),dexmedetomidine group(group D).In group D,dexmedetomidine were given intravenously at 0.5μg/kg over 10 minutes before anesthesia induction,followed by intravenous infusion at the rate of 0.6μg/kg.h.Equal volumes of normal saline were given in group O.In group O and group D,during both TLV and OLV,patients received the ventilation protocol consisting of VT of 9ml/kg,Zero PEEP,FiO2 =1.0,inspiration to expiration ratio(I:E)of 1:2,respiratory rate was adjusted to maintain PETCO2 between 35 and 45 mmHg.Observation indexes:(1)A-SBP、A-DBP、HR、SpO2 in all groups were monitored and recorded at baseline(To),at the time just before OLV(Ti),at 30min after OLV(T2),at 60min after OLV(T3),at 120min after OLV(T4)and 15min after the restoration of TLV(Ts).(2)PPeak,Pplat,Cdyn,Raw were monitored and recorded at the special time points.(3)Arterial blood samples in all groups were collected at To-T5 time points for blood gases analyse and oxygenation index was calculated.(4)The concentration of serum TNF-a,IL-6,HMGB1,MPO,MDA and SOD were measured at the time points of T0,T1,T3,T4,2 hours after operation(T6)and 24 hours after operation(T7).(5)The incidiences of postoperative pulmonary complications in all groups were recored on the 7th day after operation.Results:(1)Compared with group O,A-SBP,A-DBP and HR in group D were significantly decreased at T2-Ts time points(P<0.05orP<0.01).(2)Compared with Ti,Ppeak,Ppiat,Raw at T2～T4 time points in all groups were significantly increased,while Cdyn were obviously decreased(P<0.01).Compared with group O,Raw at T2-T4 time points in group D was significantly decreased(P<0.01).(3)PaO2 at Ti and T5 in group D was singnificantly higher than that in group O(P<0.05).Compared with group O,OI at Ts in group D was significantly increased(P<0.05).(4)Compared with group O,the level of TNF-a,IL-6,MPO at T3～T4,T6～T7 in group D were obviously decreased(P<0.05or P<0.01),the concentration of HMGB1 at T6～T7 in group D was also obviously decreased(P<0.05 or P<0.01).Compared with group O,the concentration of MDA at T3～T4,T6～T7 in group D was significantly decreased(P<0.05or P<0.01),while the level of SOD at T4,T6～T7 in group D was significantly higher than that of in group O(P<0.05or P<0.01).(5)The incidience of postoperative pulmonary complications was 20%,5%respectively in group O and group D,there was no significantly difference between the two groups(P>0.05).Conclusions:Dexmedetomidine could effectively suppress inflammatory and oxidative stress response and it could also decrease Raw and improve oxygenation in patients undergoing thoracoscopic lobectomy under conventional one lung ventilation mode.However,it did not significantly decrease the incidience of PPCs.Part III:Protective effects of dexmedetomidine on the lungs in patients undergoing thoracic surgery under lung protective ventilation strategyObjective:To observe the effects of dexmedetomidine on respiratory mechanics,oxygenation,inflammatory response,oxidative stress and postoperative pulmonary complications in patients undergoing thoracic surgery under lung protective ventilation strategy.Methods:Forty ASA I or II patients aged 40～64 yr,BMI 20～25 scheduled for thoracoscopic lobectomy were randomly divided into 2 groups(n=20 each):lung protective ventilation strategy group(group P)and dexmedetomidine combined with lung protective ventilation strategy group(group D-P).In group D-P,dexmedetomidine were given intravenously at 0.5μg/kg over 10 minutes before anesthesia induction,followed by intravenous infusion at the rate of 0.6μg/kg.h.Equal volumes of normal saline were given in group P.In group P and group D-P,patients received VT of 6ml/kg,PEEP= 5cmH2O,FiO2 = 0.7,I:E of 1:2,respiratory rate was adjusted to maintain PETCO2 between 35 and 45 mmHg during TLV and OLV.Observation indexes:(1)A-SBP、A-DBP、HR、SpO2 in all groups were monitored and recorded at baseline(To),at the time just before OLV(Ti),at 30min after OLV(T2),at 60min after OLV(T3),at 120min after OLV(T4)and 15min after the restoration of TLV(T5).(2)Ppeak,Ppiat,Cdyn,Raw were monitored and recorded at the special time points.(3)Arterial blood samples in all groups were collected at T0～T5 time points for blood gases analyse and oxygenation index was calculated.(4)The concentration of serum TNF-a,IL-6,HMGB1,MDA,MPO and SOD were measured at the time points of T0,Ti,T3,T4,T6,T7.(5)The incidiences of postoperative pulmonary complications in all groups were recored on the 7th day after operation.Results:(1)Compared with group P,A-SBP,A-DBP and HR in group D-P were significantly decreased at T2-T5 time points(P<0.05or P<0.01),SpO2 in group D-P was significantly increased at T2(P<0.01).(2)Compared with T1,Ppeak,Ppiat,Raw at T2-T4 time points in all groups were significantly increased,while Cdyn were obviously decreased(P<0.01).(3)Compared with group P,PaO2 at T1～T5 in group D-P was significantly increased(P<0.05or P<0.01).Compared with group P,OI at T1～T5 in group D-P was significantly increased(P<0.05or P<0.01).(4)Compared with group P,the level of TNF-a,IL-6,MPO at T3～T4,T6～T7 in group D-P were obviously decreased(P<0.05 or P<0.01),the concentration of HMGB1 at T6～T7 in group D-P was significantly decreased(P<0.01).Compared with group P,the concentration of MDA at T3～T4,T6～T7 in group D-P was significantly decreased,while the level of SOD at the same time points in group D-P was significantly increased(P<0.05or P<0.01).(5)The incidience of postoperative pulmonary complications was 10%,0%respectively in group P and group D-P,there was no significantly difference between the two groups(P>0.05).Conclusions:By using LPVS,dexmedetomidine could effectively suppress stress response induced by thoracic surgery and OLV and it could further improve oxygenation,attenuate inflammatory and oxidative stress response.Whereas there was no significantly decrease in PPCs. |
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