| Objective:To investigate the effects of volatile anesthetics on human regional cerebral glucose metabolism and regional cerebral blood flow with brain functional imaging and electrophysiology technology, and explore the main targets that sensitive to volatile anesthetics in human brain, and provide new evidence for illustrating the mechanism of general anesthesia. Part 1 Effect of volatile anesthetics on human regional cerebral glucose metabolism (rCMRglu) ParticipantsEight volunteers, whose mean age was 28±5 years, were nonsmokers, in excellent medical condition, and each was classified as American Society of Anesthesiologists physical status 1. All were screened carefully and found to have no evidence of previous psychiatric history or significant medical problems. Participants were asked to avoid caffeine and all other medications for at least 48h before each scan.Anesthetic proceduresThe research laboratory was a small sound-shielded room with dim lighting. The participants wore blindfolds and headphones during both awake and anesthetized uptake periods to minimized any visual and auditory input.Monitoring electrocardiogram, noninvasive blood pressure, pulse oximeter, end-tidal carbon dioxide, temperature, Bilateral Frequency Spectrum Index (BIS) and pericardial stethoscope.An intravenous catheter was inserted for FDG administration.For the anesthesia condition, subjects were connected to a Drager Julian anesthesia machine via a semiopened breathing system, and 100% inspired oxygen was administered using a soft rubber facemask for 3 min before anesthesia was induced. Volatile anesthetic was delivered into the breathing system using a standard vaporizer, and end-tidal expired concentrations were monitored. Participants maintained spontaneous ventilation during anesthesia.Induction proceeded in a slow and deliberate step-wise manner. The anesthetic agent was increased in 0.1%(expired) increments approximately every 5min until a stable percent expired volatile anesthetic concentration was obtained at the target concentration (0.5MAC, 1.0MAC). Once stable under the target level of volatile anesthesia, an additional 12 min of anesthesia time was allowed to ensure that the brain anesthetic partial pressure was constant. The participants were given 0.055mCi/kg 18FDG intravenously over a period of 1 min. The expired volatile anesthetic concentration then remained constant for the subsequent 32 min period. After this uptake period, the volatile anesthetic was discontinued and theparticipants were allowed to emerge from anesthesia and being taken to the PET scan 10 ± 5 min later. Positron emission tomography proceduresEight volunteers each underwent three PET scans: one scan assessed awake-baseline metabolism and other two scans assessed metabolism during 0.5MAC and 1.0MAC volatile anesthetics (enflurane, isoflurane, desflurane). Scans were obtained with a PHILIPS CPET Plus scanner using the 15fluorodeoxyglucose technique.ROIs and counts were taken for the frontal lobe, temporal lobe, occipital lobe, parietal lobe, thalamus, basal ganglia, lingual gyrus, cingulated gyrus, cerebellum, hippocampus, pons and whole brain. Results:Experiment 1: Effects of isoflurane anesthesia on human rCMRglu1. Varities of physiologic values during isoflurane anesthesia Compared with awake condition, BIS decreased from 94.3±3.7to 70.8±6.4(P<0.05)and 45.3±6(P<0.01)at 0.5MAC and 1.0 MAC during isoflurane anesthesia,respectively. 0.5 MAC vs 1.0 MAC, BIS also decreased significantly (P<0.01) .Other physiologic values had no change among the three conditions.2. Varities of CMRglu during isoflurane anesthesiaWhole brain CMRglu count was 1951.8±154.1 in awake conditiom, isoflurane anesthesia reduced CMRglu 17 % to 1619.9±126.2(P<0.05)at 0.5MAC lever and 21% to 1424.8±220.4 (P <0.01) at l.OMAC lever.3. varities of rCMRglu during isoflurane anesthesia 0.5MAC vs awake, rCMRglu decreased throughout the brain,mainly in thalamus (56%), lingual gyrus (50%) and cingulated gyrus (51)% (p<0.01).1.0 MAC vs 0.5MAC, rCMRglu decreased significantly but uniformly (p<0.05)Experiment 2: Effects of enflurane anesthesia on human rCMRglu1. Varities of physiologic values during enflurane anesthesia Compared with awake condition, MAP and BIS decreasedduring enflurane anesthesia. MAP decreased from 75.6±4.3mmHg to 68.9±5.5mmHg ( P<0.05 ) at 0.5 MAC enflurane, and to 64.8±7.2mmHg(P<0.01 )at 1.0 MAC; BIS decreased from 95.5±3.5 to 69.5±5.4 (P<0.05) and 45.5±4.7 (p<0.01) at0.5MAC and 1.0 MAC,respectively. 0.5 MAC vs 1.0 MAC, BIS also decreased significantly (P<0.01) .Other physiologic values had no change among the three conditions.2. Varities of CMRglu during enflurane anesthesiaWhole brain CMRglu count was 1951.8±154.1 in awake conditiom, enflurane anesthesia reduced CMRglu 14 % to 1752.6±203.2(P<0.05)at 0.5MAC lever and 28% to 1682.2±132.2 (P<0.01) at l.OMAC lever.3. Varities of rCMRglu during enflurane anesthesia 0.5MAC vs awake, rCMRglu decreased throughout the brain.especially thalamus, cingulate gyrus, frontal lobe, cuneus, precuneus and pons (P<0.01), decreased 32, 29, 27, 23, 21 and 14%, respectively.1.0 MAC vs 0.5MAC, rCMRglu decreased significantly but uniformly (P<0.05) . Experiment 3: Effects of desflurane anesthesia on humanrCMRglu1. Varities of physiologic values during desflurane anesthesiaCompared with awake condition, BIS decreased from 92.2±3.6to 70.8±6.2 (P<0.05) at 0.5 MAC desflurane and to 45.5±6.9(P<0.01) at 1.0 MAC. 0.5 MAC vs 1.0 MAC, BIS also decreasedsignificantly (P<0.01) .Other physiologic values had no changeamong the three conditions.2. Varities of CMRglu during desflurane anesthesiaWhole brain CMRglu count was 1951.8±154.1 in awake conditiom, desflurane anesthesia reduced CMRglu 21 % to 1645.1±201 (P<0.05) at 0.5MAC lever and 34% to 1280.7±143 (P<0.01) at l.OMAC lever.3. Varities of rCMRglu during desflurane anesthesia 0.5MAC vs awake, rCMRglu decreased throughout the brain.especially thalamus, occipital lobe and lingual gyrus(P<0.01), decreased from 3045.3±164,2867.7±107 and 3076.6±163 to 1938.2±119(36.4%), 2002.8±169(30.2%) and 2227.8±158(27.6%), respectively.1.0 MAC vs 0.5MAC, rCMRglu decreased significantly but uniformly (P<0.05) .Part 2. Effects of volatile anesthetics on human regionalcerebral blood flow (rCBF)Participants: Eight volunteers, selecting standard was same aspart 1.Anesthetic procedures:Electrocardiogram, noninvasive blood pressure, pulse oximeter, end-tidal carbon dioxide, temperature and Bilateral FrequencySpectrum Index (BIS) were monitored throughout the procedure.An intravenous catheter was inserted for 99mTc-ECD adminitration.For the anesthesia condition, subjects were connected to a Drager Julian anesthesia machine via a semiopened breathing system, and 100% inspired oxygen was administered using a soft rubber facemask for 3 min before anesthesia was induced. Volatile anesthetic was delivered into the breathing system using a standard vaporizer, and end-tidal expired concentrations were monitored. Participants maintained spontaneous ventilation during anesthesia.Induction proceeded in a slow and deliberate step-wise manner. The anesthetic agent was increased in 0.1%(expired) increments approximately every 5min until a stable percent expired volatile anesthetic concentration was obtained at the target concentration (0.5MAC, 1.0MAC). Once stable under the target level of volatile anesthesia, an additional 12 min of anesthesia time was allowed to ensure that the brain anesthetic partial pressure was constant. The participants were given 0.6mCi 99mTc-ECD intravenously over a period of 1 min. The expired volatile anesthetic concentration then remained constant for the subsequent 10 min period. After this uptake period, the volatile anesthetic was discontinued and the participants were allowed to emerge from anesthesia and being taken to the SPECT scan 30±10 min later. SPECT procedure:Each volunteer underwent three SPECT scans during awake condition, 0.5MAC and 1.0MAC inhalational anesthesia. Scans were obtained with a GE millennium MG scanner using the99mTc-ECD technique. Outlined the ROI of frontal lobe, parietallobe, temporal lobe, occipital lobe, midbrain, cerebellum,thalamus, hippocampal gyrus, basal ganglia, cingulated gyrus andlingulate gyrus in the brain slices. The counts of the interestregions of were recorded.Results:Experiment 1: Effects of isoflurane anesthesia on human rCBF1. Varities of physiologic values during isoflurane anesthesia Compared with the awake condition, BIS decreased from94.6±3.0 to 68.1±5.5 (P<0.05) at 0.5 MAC isoflurane and to 42.3±4.7 (P<0.01) at 1.0 MAC. BIS also decreased significantly (P<0.01) at l.OMAC compared with 0.5MAC. Other physiologic values had no change among the three conditions.2. Varities of CBF during isoflurane anesthesiaThe average counts of whole brain CBF are 132.8±36.4, 129.6±38.5 and 130.3±30.2 during awake, 0.5MAC and l.OMAC isoflurane anesthesia, respectively. There were no statistical difference among the three conditions.3. Varities of rCBF during isoflurane anesthesiaThere were no significant difference in rCBF count among the three conditions.Experiment 2: Effects of enflurane anesthesia on human rCBF 1. Varities of physiologic values during enflurane anesthesia Compared with the awake condition, BIS decreased from 94.5±2.2 to 75.1±3.7 (P<0.05) at 0.5 MAC enflurane and to 42.6±5.8 (P<0.01) at 1.0 MAC. 0.5 MAC vs 1.0 MAC, BIS also decreased significantly (P<0.01) .Other physiologic values had no change among the three conditions.2. Varities of rCBF during enflurane anesthesiaThe average counts of whole brain CBF are 135.2 ± 27.8, 141.3 ± 28.8 and 139.6 ± 27.4 during awake, 0.5MAC and l.OMAC enflurane anesthesia, respectively. There were no statistical difference among the three conditions.3. Varities of rCBF during enflurane anesthesiaThere were no significant difference in rCBF count among the three conditions. Experiment 3: Effects of desflurane anesthesia on human rCBF1. Varities of physiologic values during desflurane anesthesia Compared with the awake condition, BIS decreased from92.2±3.6 to 70.8±6.2 (P<0.05) at 0.5 MAC desflurane and to 45.5±6.9 (P<0.01) at 1.0 MAC. 0.5 MAC vs 1.0 MAC, BIS also decreased significantly (p<0.01) .Other physiologic values had no change among the three conditions.2. Varities of CBF during desflurane anesthesiaThe average counts of whole brain CBF are 127.5 ± 23.1, 130.8±25.4 and 128.8 ± 22.9 during awake, 0.5MAC and l.OMAC desflurane anesthesia. There were no statistical difference among the three conditions.3. Varities of rCBF during desflurane anesthesiaThere were no significant difference in rCBF count among the three conditions.Conclusions:1. We have studied the effects of volatile anesthetics (isoflurane, enflurane, and desflurane) on rCMRglu with PET in healthy volunteers, the results show that volatile anesthetics (isoflurane,...
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