The Experimental Study Of Pharmacodynamics On Bolus Intracarotid Propofol

Study 1:Establishment of a modified high-performance liquid chromato- graphy for the concentration of propofol in serum.Objects:To develop a high-performance liquid chromatography for the determination of propofol in serum and provide a rapid,sensitive and simple method for determining the concentration of propofol in serum during clinical anesthesia. Methods: Serum samples were precipitated with 20﹪perchloric acid and then centrifugated to obtain 50μL of the supernatant for analysis by HPLC coupled with fluorescence detection. The analysis was performed with a C18 reversed-phase column using a acetonitrile-water(90:10)phase delivered at 1.0 mL/min, with the excitation wavelength of 276 nm and emission wavelength of 310 nm.Results : The calibration curves were linear(r=0.9975) within the concentration range of 0.05-10μg/mL, the limit of quantification for propofol was 50 ng/mL ,and intra- and inter-day precision were between±15%. Conclusion: The method is a rapid,sensitive and simple for the determination of propofol in serum during clinical anesthesia.Study 2:Establishment of a novel anesthetic procedure with bolus intracarotid injection of propofol in dogsObjects: To compare the effect of bolus propofol between internal carotid artery and forearm vein injection on circulatory and respiratory function, and the dosage of propofol until the auditory evoked potential index decreased to 7±2. Methods: Eight dogs were anesthetized by internal carotid artery or forearm vein bolus injection of propofol until the auditory evoked potential index decreased to 7±2 . The time of consciousness loss and recovery,dosage of propofol,mean arterial pressure,heart rate,respiration rate,end-tidal carbon dioxide and SpO2 were continuously monitored until the auditory evoked potential index decreased to 7±2.The Changes in the variables were analyzed at the different four points, namely the baseline,upon loss of consciousness,and recovery of auditory evoked potential index and recovery of consciousness.Results: The time of the auditory evoked potential index decreasing to 7±2 and the time of consciousness recovery by intracarotid propofol administration were shorter than those by intravenous administration( P<0.05). When the consciousness losed, the dosage (6.1±2.3 mg ) of propofol by intracarotid administration was significantly less than the dosage (72.9±24.3 mg ) of propofol by intravenous administration (P=0.0001). Compared to intravenous administration, the changes of hemodynamics and index of respiratory function by intracarotid administration were more stable. Conclusion: Intracarotid administration of propofol with less dosage could produced the same anesthetic effect as intravenous administration of propofol. Moreover, the changes of hemodynamics and index of respiratory function by intracarotid administration of propofol were more stable than intravenous administration of propofol.Study 3: Changes of concentration of propofol in main target organ during anesthetic induction with intracarotid or intravenous administrationObjects: To compare the concentration of propofol in internal carotid artery and internal jugular vein with intracarotid or forearm vein infusion at constant speed when the auditory evoked potential index decreased to 7±2. Methods: Eight dogs were anesthetized with intracarotid or peripheral venous administration of propofol at the constant rate of 0.1 mg·kg-1·min-1 until the auditory evoked potential index decreased to 7±2. The concentration of propofol in contralateral internal carotid artery and internal jugular vein was measured respectively at 2, 4, 6, 8, 10 min after administration of propofol and loss of consciousness by HPLC described in experiment one. Results: Compared to intracarotid administration, the concentration of propofol in contralateral internal carotid artery and internal jugular vein was lower than those by forearm vein administration. There is no significant differences between the concentration of propofol in contralateral internal carotid artery and internal jugular vein for the same drug administration. Conclusion: Intracarotid administration achieved the balance of cerebral uptake much more quickly than intravenous administration and cerebral propofol uptake is time dependent when administered at a constant infusion rate. The balance of cerebral uptake of propofol lagged benind the balance of propofol concentration in the artery. Propofol was not metabolized in brain.