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Objective@#To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.@*Methods@#Forty-five healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 3 groups by a random number table method: sham operation group (Sham group, n=5), bupivacaine group (B group, n=20), and lipid emulsion group (L group, n=20). Cardiac arrest was induced by intravenously injecting 0.4% bupivacaine 30 mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L, and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B, followed by a 3-min infusion of 1 ml·kg-1·min-1in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure, heart rate, mean arterial pressure, rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0), time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC, and left ventricular tissues were obtained for determination of the expression of Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3, cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.@*Results@#Compared with Sham group, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated, and the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P<0.05). Compared with B group, the rate of successful resuscitation and survival rate were significantly increased, Tr was shortened, systolic blood pressure, heart rate, RPP and RPPh were increased after ROSC, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated, the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was down-regulated (P<0.05), no significant change was found in To or Ts (P>0.05), and the pathological changes of myocardium were significantly attenuated in L group.@*Conclusion@#The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.
ABSTRACT
Objective To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.Methods Forty-five healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 3 groups by a random number table method:sham operation group (Sham group,n =5),bupivacaine group (B group,n =20),and lipid emulsion group (L group,n =20).Cardiac arrest was induced by intravenously injecting 0.4％ bupivacaine 30mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L,and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B,followed by a 3-min infusion of 1 ml · kg-1 · min-1 in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure,heart rate,mean arterial pressure,rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0),time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC,and left ventricular tissues were obtained for determination of the expression of Bax,Bcl-2,cleaved caspase-9,cleaved caspase-3,cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.Results Compared with Sham group,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated,and the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P＜0.05).Compared with B group,the rate of successful resuscitation and survival rate were signif-icantly increased,Tr was shortened,systolic blood pressure,heart rate,RPP and RPPh were increased after ROSC,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated,the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was downregulated (P＜0.05),no significant change was found in To or Ts (P＞0.05),and the pathological changes of myocardium were significantly attenuated in L group.Conclusion The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.
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Objective To compare the degree of pain in patients after radical gastrectomy under different anesthetic regimens.Methods One hundred and two ASA Ⅰ or Ⅱ patients of both sexes,aged 50-75 yr,weighing 45-70 kg,undergoing elective radical gastrectomy,were randomly divided into 3 groups ( n =34 each):general anesthesia (GA) group,combined general-subcostal transversus abdominis plane block (CGTA) group and combined general-epidural anesthesia (CGEA) group.The patients were sent to the postanesthesia care unit (PACU) after tracheal extubation,and the VAS score on arrival in the PACU was recorded.The degree of pain was evaluated by VAS score,and when VAS scores ＞ 3,the patients received intravenous morphine titration.When VAS scores ≤ 3,morphine titration was stopped and all the patients were connected to patient-controlled intravenous analgesia and/or epidural analgesia pump.The total amount of morphine consumed was recorded at the end of titration,and the occurrence of adverse reactions was also observed.Results Compared with groups GA and CGTA,the incidence of moderate to severe postoperative pain was significantly decreased in group CGEA (P ＜0.01).The incidence of severe postoperative pain,the VAS score on arrival in the PACU and the total amount of morphine consumed were decreased gradually in groups GA,CGTA and CGEA ( P ＜ 0.01 ).The incidence of sedation was significantly lower in group CGEA than in group GA (P ＜ 0.01 ).There were no significant differences in the other adverse reactions among the three groups ( P ＞ 0.05 ).Conclusion The degree of pain is reduced gradually in patients after radical gastrectomy under GA,CGTA and CGEA.