The Cerebral Uptake And Regional Distribution Of Propofol Under Different Depth Of Anesthesia In Dogs

Propofol is a relatively new intravenous anesthetic and has been widely used in general anesthesia induction and maintenance.Recently,it is popularly used as a sedative agent in the intensive care unit.As we know,brain is the effective organ of intravenous anesthetics,the research of cerebeal uptake and distribution is favourable to explore the mechanism of general anesthesia.In 1988,Upton put forward the concept of cerebral uptake and the fundamental research method of mass balancing principles.The research about cerebral uptake of propofol usually bases on the mass balance principles.By measuring the propofol concentrations in arterial and venous blood of cerebral circulation,we can calculate the cerebral concentrations and evaluate the cerebral uptake of propofol.Based on the mass balancing principle,some scholars had introduced the research of the cerebral uptake of propofol in the late-1990s.The basic goal is to explore the rule of pharmacokinetics and pharmacodynamics of propofol,improve and renew existed method of propofol intravenous anesthesia.The main research technique is to measure the propofol concentration of artery blood and the venous blood using high-pressure liquid chromatograph(HPLC) and to evaluate the cerebral uptake of propofol by calculating the areas under the concentration-time curves entering and leaving the brain.However,the character of regional distribution of propofol in the brain can not be revealed yet by this method.To improve the research method of cerebral uptake,the propofol concentrations in different parts of the brain must be detected directly by anatomy.Shyr and Larsson had compared the propofol distribution in the mouse brain tissues respectively,the propofol concentrations were measured by high-pressure liquid chromatography ultra-violet spectroscopy(HPLC-UV) method.They discovered that the midbrain was different to the other brain function area in intaking the medicine.It may be injected factor,brain uptake condition,and species of experimental animal that influence the cerebral uptake and distribution of propofol.The ever experiments used the SD mouse as the experimental animal.The differences between the mouse brain structure and function and the human brain's are obvious,so it is difficulty to generalize the experimental result in human being.Now it is necessary to study with a more high-grade animal.The function district and the structure of dog brain are similar with that of the human brain,and the volume and the quality of dog brain are bigger than that of the mouse brain's so as to get the obvious regional tissues.The chief aim of this study is to mesure the propofol concentrations of different cerebral tissues using HPLC-UV and to investigate the cerebral uptake and regional distribution of propofol under different depth of anesthesia in dogs.Material and methods12 healthy male dogs aged 12-18 months were divided randomly into two groups(group S and A).The venous channel was established in the great saphenous vein of the right posterior limb.Propofol was intravenously injected respectively at a single bolus 4.5mgo·kg^-1 and 7mg·kg^-1 in group S and group A in 15 sec.When the animal's eyes closed without stimulation to the end of its tail by hemostat in group S and the eyelid reflex disappeared in group A,the blood samples were taken from the right internal carotid and internal jugular vein for determination the concentrations of propofol.Then the animal was scarificed immediately by decapitation.The frontal lobe,parietal lobe,temporal lobe,hippocampus,cingulate gyms,thalamus,midbrain,pons and cerebellum were further dissected for determination the concentrations of propofol.Propofol concentration was determined by HPLC-UV.External standard was a control article of propofol.The analysis was performed with a Dikma Diamonsil C₁₈ reverse-phase column(200×4.6mm,5μm) and a 2996 Waters ultraviolet detector (270nm).The solvent system was acidum aceticum-methanol- ammonium acetate at flow rate of 1ml·min^-1.The brain samples were extracted with acetonitrile(2ml·g^-1) and homogenized and the blood samples were extracted with acetonitrile(di-volume). After being centrifuged,the supernatant was submitted to HPLC analysis.Measurement data were expressed as mean±standard deviation.All data were analysed with the Statistics Package for Social Sciences(SPSS,version 13.0 for WINDOWS;SPSS Inc.,Chicago,IL,USA).Differences were considered statistically significant when P was less than 0.05.We used the one-way AVON and factorial analysis to test for differences.Multiple comparisons were analyzed by SNK test.Results1.The propfol concentration in blood plasma:In group S,the concentration of propofol in internal carotid artery (8.19±0.13μg.ml^-1) was higher than that in internal jugular vein blood plasma (3.19±0.07gg.ml^-1)(t=81.381,P=0.000).In group A,the concentration of propofol in internal carotid artery(11.71±1.63μg.ml^-1) was higher than that in internal jugular vein blood plasma(5.42±0.80μg.ml^-1)(t=8.460,P=0.000).The plasma concentrations of propofol does not exist interaction with dose(F=2.975,P=0.100).2.The propofol concentration in brain tissues:In group S,the propofol concentrations of the frontal lobe,parietal lobe, temporal lobe,hippocampus,cingulate gyrus,thalamus,midbrain,pons and cerebellum were 3.63±0.12,3.50±0.13,3.36±0.06,3.08±0.50,3.78±0.85,4.33±0.33, 4.15±0.87,4.90±0.93 and 3.67±0.81g.g^-1 respectively.The propofol concentrations is highest in pons and lowest in hippocampus(P＜0.05).In group A,the propofol concentrations of the frontal lobe,parietal lobe, temporal lobe,hippocampus,cingulate gyrus,thalamus,midbrain,pons and cerebellum were 8.10±1.24,8.08±1.32,8.30±1.85,5.59±0.75,8.34±1.87,10.98±3.00, 8.55±1.46,8.49±1.35 and 7.93±1.10μg.g^-1respectively.The propofol concentration is highest in thalamus and lowest in hippocampus(P＜0.05).Apparente differences were observed in the propofol concentrations of tauto-brain tissues between group S and A(P＜0.05).The brain tissues concentrations of propofol exist interaction with dose(F=5.145,P=0.000).Conclusions1 Under different depth of anesthesia at a single bolus intravenous injection of propofol,the difference of propofol concentrations between internal carotid artery and jugular vein is significant and show that the cerebral uptake of propofol is underway. 2 Under above condition,the cerebral distribution of propofol is unequal.The propofol concentration is highest in pons when the animal's eyes closed without stimulation and in thalamus when the eyelid reflex disappeared respectively,and lowest in hippocampus under the both anesthesia conditions.