The Cerebral Uptake And Distribution Of Propofol During Propofol Intravenous Anesthesia At A Single Bolus In Dogs

Propofol is a relatively new intravenous anesthetic.Since it is first introduced in 1977,propofl has been the most common venous anesthetic as an induction and maintenance agent.The research of cerebral uptake of propofol is basing on mass balance principles usually.By determinations of propofol concentrations in arterial and venous blood of cerebral circulation,we can calculate the feature of the cerebral uptake of propofol indirectly.But the character of regional distribution of propofol in the brain can not been revealed by this method.To improve the research of cerebral uptake of propofol, the propofol concentrations in different parts of the brain must be detected directly by anatomy.Many researches have been done to investigate the anesthetic mechanism of propofol,but the mechanism is not been made out very clearly until today.In the past decdade,a large body of experimental observations have accumulated that the central GABA_A receptors represent an important target in mediating the anesthetic mechanism of propofol.The central GABA_A receptors scatter in the brain,but it is more intensive in some cerebral tissues than the others.Using PET,it has been found that the regional cerebral glucose metabolism and regional cerebral blood flow is depressed more significantly in some of the cerebral tissues.Basing these researches, it can be assumed that propofol concentrations are discordant in various cerebral tissues.Therefore,the cerebral uptake and regional distribution of propofol must be investigated for the understanding of its anesthetic mechanism.No evidence can prove whether other anesthetics can influence the cerebral uptake and regional distribution of propofol.But it is very important for the guide to the clinical use of propofol.It have found that sufentanil has many advantages combining with propofol in clinical anesthesia.Recently,it has been found that sufentanil has different effect on various cerebral tissues,and it can disturb the cerebral metabolism and cerebral blood flow.Because cerebral blood flow is involved in the cerebral uptake of propofol,it can be assumed that sufentanil may have effect on the cerebral uptake and regional distribution of propofol.This study is firstly aimed to investigate the cerebral uptake and regional distribution of propofol.Secondly,this study is aimed to explore the influence of sufentanil on the cerebral uptake and regional distribution of propofol.Meanwhile, we improve the method of HPLC analysis for cerebral tissue and blood plasma.Methods and materials12 healthy male dogs aged 1 year in two randomized groups(group A and B) were enrolled in this study.The venous channel was established in the great saphenous vein of the right posterior limb in dogs.Anesthesia was induced with propofol at a single bolus(7mg·kg^-1)in 15 sec in group A.In group B,after the sufentanil(1μg·kg^-1)was injected,propofol was infused at a single bolus(7mg·kg^-1)in 15 sec.The blood samples were taken from the right internal carotid and internal jugular vein when the eyelid reflex disappeared in group A and B for the determinations of propofol concentrations by HPLC.The dogs were killed by decapitation when the eyelid reflex disappeared.The frontal lobe,parietal lobe,temporal lobe,hippocampus, cingulate gyrus,thalamus,midbrain,pons,cerebellum were dissected respectively for the determinations of propofol concentrations by HPLC.Propofol concentrations were determined by modified HPLC-UV.External standard was a control article of propofol.The analysis was performed with a Dikma Diamonsil Ca8 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.The blood samples were extracted with acetonitrile(di-volume).After being centrifuged,the supernatant was submitted to HPLC analysis.Measurement data are expressed as mean±standard deviation.All datas were computed with SPSS 10.0 for windows.Differences were considered statistically significant when P was less than 0.05.We used the two-way AVON and paired t-test to test for differences for measurement data.Post Hoc multiple comparisons were analyzed by using SNK test.Results1 The propfol concentration in blood plasma:In group A,the propofol concentrations in internal carotid artery and internal jugular vein blood plasma were 11.711±1.634,5.424±0.802μg·ml^-1respectively.The propofol concentrations in internal carotid artery were higher(P＜0.05).In group B,the propofol concentrations in internal carotid artery and internal jugular vein blood plasma were 11.700±1.585,5.444±0.780μg·ml^-1respectively.The propofol concentrations in internal carotid artery were higher(P＜0.05).The propofol concentration in internal carotid artery of group A is same as that of group B(P＞0.05).2 The propofol concentration in brain tissues:In group A,the propofol concentrations in the frontal lobe,parietal lobe, temporal lobe,hippocampus,cingulate gyms,thalamus,midbrain,pons,cerebellum, were 8.21±1.05,8.28±1.22,8.27±1.37,5.83±1.08,8.39±1.21,10.38±1.76, 9.37±1.17,9.26±1.35,7.73±1.86μg·g^-1μg·ml^-1respectively.The propofol concentrations were highest in thalamus and lowest in hippocampus(P＜0.05).In group B,the propofol concentrations in the frontal lobe,parietal lobe, temporal lobe,hippocampus,cingulate gyms,thalamus,midbrain,pons,cerebellum were 8.154±1.542,8.125±1.572,8.330±1.906,5.605±0.729,8.351±1.738,11.055±3.325,8.634±1.944,8.574±1.902,7.968±1.323μg·g^-1respectively.The propofol concentrations were highest in thalamus and lowest in hippocampus(P＜0.05).No differences were observed in propofol concentrations in brain tissues between group A and B(P＞0.05).Conclusions1 The HPLC-UV assay combining with precipitation method can be used for determination of propofol concentration in blood plasma and brain tissue.2 When the effective anesthesia is established,the cerebral uptake of propofol is unstable during propofol intravenous anesthesia at a single bolus in dogs,and the propofol concentrations are discordant in various cerebral tissues,highest in the thalamus,lowest in the hippocampus.3 Sufentanil has no influence on the cerebral uptake and regional distribution of propofol in dogs.