| There is homology in between pigs and adults in comparative medicine and they are quite similarly in anatomy, physiology, biochemistry and disease occurrence mechanism from abundance researches. So pigs used as experimental animals not only in researches of cardiovascular system, digestive system, genital system, endocrinium, presbyatrics, hematology, trophology, skin, dentistry, ophthalmology, radiation creature and immunology but also in heterogeneity organ transplantation. Without well anesthetic effect pigs could not bear pain stimulus during the surgery such as in the researches of medical animal model, transgenic animal, clone, organ transplantation, embryo transplantation so that all of above could not finish, and forthcoming anesthetis could reach the requirements. Combined anesthesia was invented based on balanced anesthesia theory by the veterinary surgery department of Northeast Agricultural University. Its key component is ketamine which was combined with midazolam, xylidinothiazoline and qingtongning. It is necessary to determine the clinic effect and parameters of the combined anaesthesia in order to offer more reference for clinical medication reasonablely before widely used in clinic.Intensive care monitor and electroencephalograph were used to monitor the temperature, heart rate, breathing rate, saturation of blood oxygen, blood pressure, electrocardiogram and electroencephalogram during anesthesia in miniature pigs; the effects of ketamine combined anesthesia were evaluated after comparing with other anaesthetic such as zoletil and xylazine combined anaesthesia during the surgery; determined the blood concentration-time curve of ketamine in miniature pigs with High Performance Liquid Chromatogram(HPLC)and analyzed with software 3p87 to research the feature of pharmacokinetics.The results showed that, anesthesia induction stage of ketamine combined anesthesia was 2.9±0.8min; anesthesia stage was 88.6±10.6min, analepsia stage was 37.1±5.9min; the change range of temperature was 37.22℃to 38.42℃; the heart rate was 64.25min-1 to 94.37min-1; breathing rate was 30.25min-1 to 46.50min-1; the saturation of blood oxygen was 92.62% to 97.62%; mean arterial blood pressure was 71.37mmHg to 100.25mmHg. The effect of ketamine combined anesthesia was better than zoletil combined anesthesia through the validate experiment and provide better analgesia, sedation, muscle relaxation effect for surgery. This experiment established the method to determine the concentration of ketamine in plasma with HPLC in miniature pigs. The pre-processing of the sample is convenient, practice, high recovery rate and reliable method. This method is suitable for monitoring blood concentration in clinic anesthesia and the research of pharmacokinetics. Using this method to determine the concentration of ketamine, the linear correlation during 0.2μg/ml~3.2μg/ml was well and correlation coefficient(R2) of standard curve was exceed 0.99. The pharmacokinetics feature of Ketamine was corresponded with first order kinetics single compartment model after intramuscular injection with ketamine combined anesthesia. The main pharmacokinetics parameters of Ketamine were T1/2=9.003±1.032min, Cmax=2.871±0.853μg/mL, T ( peak ) =4.684±0.042min, V/F=0.243±0.012(mg/kg)/(μg/mL), AUC=53.477±5.368(μg/ml)·min, T1/2(Ka)=1.515±0.015min.To sum up, ketamine combined anesthesia has well analgesia, sedation and muscle relaxation effect, little influence to physiological function, widely safety margin. And it can satisfy the need in clinical anesthesia and make use of clinical practice of miniature swine. We could conclude from the pharmacokinetics parameters, ketamine was absorbed quickly after injecting the combined anesthetic by muscle, distributed fast to organizations and eliminated fast, but the organization concentration was lower than plasma concentration. |
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