| Objective:At different altitudes,the lose and recovery of the rat’s righting reflex were used as the criteria for anesthesia induction and arousal.Through the establishment of high performance liquid chromatographyand blood gas analysis to understand the influence of different altitudes on the pharmacokinetics of propofol.Method:This study intends to conduct animal experiments,and randomly divide rats into groups P and B at different altitudes.The time for the disappearance and recover of the rat’s righting reflex was taken as the time for anesthesia induction and awakening,and recorded.In group P,0.3ml of venous blood was collected at the following time points for HPLC analysis: before administration,2 minutes after administration,when the righting reflex disappeared,4,8,12,20,30,60 minutes after administration,When the reflex restored,2,15,30,60 minutes after stopping the drug.Group B collected 0.4ml of venous blood at the following time points for blood gas analysis: before administration,2 minutes after administration,when the righting reflex disappeared,4,8,12,20,30,60 minutes after administration,and when the righting reflex recovered,2,15,30,60 minutes after stopping the drug.Combining the results of high performance liquid chromatography and blood gas analysis,the pharmacokinetics of propofol in different altitude areas were analyzed,and the effect of propofol anesthesia in different altitude areas was observed.Result:1、General situation: There is no statistical difference in the baseline data of the rats used in this study.2、The induction and recovery time of propofol anesthesiaWhen rats were anesthetized with propofol,the LORR times of the P1,P2,and P3 groups were 389.50±21.86 s,414.75±12.87 s and 541.92±36.18 s,respectively.The LORR time of P1 group was significantly shorter than P2(P<0.05)、P3 group(P<0.05).The LORR time of P2 group was significantly shorter than that in the P3 group(P <0.05).The RORR time of the P1,P2,and P3 groups were: 679.17±46.57 s,578.67±40.89 s,450.50±17.23 s.The RORR time of P1 group was significantly longer than P2(P<0.05),P3 group(P<0.05).The RORR time of P2 group was significantly longer than P3 group(P<0.05).3、Propofol plasma concentrationThe plasma concentrations of propofol at 8min,12 min,20min,30 min and 60 min after administration of P1 group were higher than those of P2 and P3 group(P<0.05).The plasma concentrations of propofol at 30 min and 60 min after administration of P2 group were higher than those of P3 group(P<0.05).The plasma concentration of propofol in the P1 group was higher than that in the P2 and P3 groups at 2min,15 min and 30 min after stopping the drug(P<0.05);The blood concentration of propofol in the P2 group was higher than that in the P3 group only2 min and 15 min after stopping the drug(P<0.05).4、Pharmacokinetic parameters of propofolCompared with the P1 group,the Cmax,T1/2 and AUC of the P2 and P1 groups were smaller than those of the P1 group(P<0.05),and the CL of the P2 and P1 groups were larger than that of the P1 group(P<0.05).Compared with the P2 group,the Cmax,AUC and MRT of the P3 group were smaller than those of the P2 group.As the altitude increased,the clearance rate of propofol in rats decreased,the half-life extended,the peak plasma concentration increased,the area under the drug-time curve increased,and the average residence time increased.5、Lactic acid value at different altitudesCompared with the B1 group in the basal state,the lactic acid values of the B2 and B3 groups were lower than those of the B1 group(P<0.05).After the start of the administration,the lactic acid values of the B1 group at each time point were higher than those of the B3 group(P<0.05),the lactic acid value of group B1 was higher than that of group B2 at 4min,8min and 60 min after administration(P<0.05),group B2 had higher lactic acid value than group B3 at 2min,12 min,20min and 30min(P<0.05).As the altitude rises,hypoxia will cause the accumulation of lactic acid in rats,and the difference between high altitude and low altitude is more obvious between higher altitude and middle altitude.After stopping the pumping of propofol,the lactic acid values of the B1 group at2 min,15min and 60 min were higher than those of the B3 group(P<0.05),and the lactic acid values of the B2 group at 15 min and 30 min were higher than those of the B3group(P<0.05).Conclusion:As the altitude increases,the induction time of propofol is shortened and the recovery time of anesthesia is prolonged,the lactic acid in the rat body increases and the metabolism slows down.The metabolic characteristics of propofol in rats under high altitude are: slow metabolism,reduced clearance(CL),prolonged half-life(T1/2),increased peak plasma concentration(Cmax),and increased area under the drug-time curve(AUC),the average residence time extension(MRT). |
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