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Meeting Abstracts  |   December 1999
Local Coupling of Cerebral Blood Flow to Cerebral Glucose Metabolism during Inhalational Anesthesia in Rats  : Desflurane versus Isoflurane
Author Affiliations & Notes
  • Christian Lenz, M.D.
    *
  • Thomas Frietsch, M.D.
    *
  • Carsten Fütterer
  • Annette Rebel, M.D.
    *
  • Klaus van Ackern, M.D.
  • Wolfgang Kuschinsky, M.D.
    §
  • Klaus F. Waschke, M.D.
  • *Research Fellow, Department of Anesthesiology and Critical Care Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany. †Candidate of Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany. ‡Professor of Anesthesiology and Chair, Department of Anesthesiology and Critical Care Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany. §Professor of Physiology and Chair, Department of Physiology, University of Heidelberg, Heidelberg, Germany. ∥Research Coordinator, Department of Anesthesiology and Critical Care Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Mannheim Germany.
Article Information
Meeting Abstracts   |   December 1999
Local Coupling of Cerebral Blood Flow to Cerebral Glucose Metabolism during Inhalational Anesthesia in Rats  : Desflurane versus Isoflurane
Anesthesiology 12 1999, Vol.91, 1720. doi:
Anesthesiology 12 1999, Vol.91, 1720. doi:
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BY the use of autoradiographic methods, we recently demonstrated in rats that sevoflurane and isoflurane both induce a decrease in glucose utilization and an increase in blood flow of the brain compared with conscious controls. 1 These effects were less pronounced for sevoflurane than for isoflurane. The local analysis revealed further that local cerebral blood flow (LCBF) is mainly adjusted to the local metabolic demands at 1 minimum alveolar concentration (MAC) and to a lesser extent at 2 MAC for isoflurane and sevoflurane. 1 Because desflurane has the lowest blood gas solubility coefficient among all volatile anesthetics available, 2 promoting a fast recovery from anesthesia, in addition to its stability in soda lime, 3 desflurane appears to be well-suited for anesthesia. Therefore, in the current investigation, our observations were extended to include desflurane.
Materials and Methods 
The current study was performed using a protocol identical to our previous investigation. 1 In brief, after approval by the institutional animal care committee, 60 male Sprague-Dawley rats (Charles River Deutschland, Sulzfeld, Germany), weighing 333 ± 40 g (mean ± SD) were randomly assigned to the following five experimental groups: group 1: conscious controls anesthetized with halothane–nitrous oxide–oxygen for femoral vessel cannulation only; groups 2 and 3: rats anesthetized by isoflurane; groups 4 and 5: rats anesthetized by desflurane (Suprane; Pharmacia & Upjohn, Erlangen, Germany; Devapor; Dräger, Lübeck, Germany) each at 1 (groups 2 and 4) or 2 MAC (groups 3 and 5) in air–oxygen (fraction of inspired oxygen [FIO2], 0.3). After femoral vessel cannulation, tracheostomy, induction of artificial ventilation, muscle relaxation using pancuronium, to preserve comparability to previous autoradiographic investigations, 4–6 the rats in groups 2–5 were allowed to equilibrate for 60 min at the desired MAC level. In the conscious group (group 1), rats recovered from halothane–nitrous oxide–oxgyen anesthesia for 3 h. Then 4-iodo-N  -methyl-[14C]antipyrine was infused over 1 min for the measurement of LCBF in 40 brain regions of interest in half of the animals of each group. The other half of the animals was treated identically, with the exception that 2-[14C]-deoxy-D-glucose was infused over 20 s for the measurement of local cerebral glucose utilization (LCGU), and the equilibration time at the desired MAC level was reduced from 60 to 45 min to obtain approximately median points of the tracer measurements for LCGU and LCBF. 7,8 At the end of the measurement periods (LCGU, 45 min; LCBF, 1 min), the animals were killed and the brains were removed, frozen, sectioned into 20-μm sections at −20°C, and autoradiographed, along with precalibrated [14C]methyl methacrylate standards. LCGU or LCBF were calculated from the local concentrations of [14C] and the time course of plasma [14C]deoxyglucose and glucose concentrations 8 (lumped constant, 0.483) or the the blood iodo[14C]antipyrine 9 (blood partition coefficient of iodoantipyrine, 0.9). 10 Mean CBF and mean CGU were determined from the average of the area-weighted means of coronal sections taken from the whole brain and spaced at distances of 200 μm. Data were analyzed by analysis of variance and t  tests (significance assumed for P  < 0.05) with Bonferroni correction. The overall relation between LCGU and LCBF in the evaluated regions was assessed by the least-squares fit of the data.
Results 
Similar to isoflurane, desflurane induced a significant decrease in mean arterial blood pressure. Other physiologic parameters were comparable between the five experimental groups. Compared with the conscious state, mean CGU was significantly reduced by both anesthetics to 48% of the control value (55 ± 5 μmol · 100 g−1· min−1) at 1 MAC desflurane (27 ± 4 μ mol · 100 g−1· min−1), to 56% of the control value at 1 MAC isoflurane (31 ± 7 μmol · 100 g−1· min−1), to 38% of the control value at 2 MAC desflurane (21 ± 2 μmol · 100 g−1· min−1), and to 40% of the control value at 2 MAC isoflurane (22 ± 4 μmol · 100 g−1· min−1). No significant difference was observed between both anesthetics at identical MAC levels. The considerable decrease in glucose utilization observed on a global level was also evident from the local values. LCGU was decreased in the majority of brain structures investigated during isoflurane anesthesia and in all brain structures investigated during desflurane anesthesia. Compared to the conscious state (88 ± 6 ml · 100 g−1· min−1) mean CBF was increased by 40% during desflurane anesthesia at 1 MAC (124 ± 27 ml · 100 g−1· min−1) and by 43% during isoflurane anesthesia (126 ± 18 ml · 100 g−1· min−1). At 2 MAC mean CBF was increased by 68% during desflurane anesthesia (148 ± 14 ml · 100 g−1· min−1) and by 70% during isoflurane anesthesia (150 ± 15 ml · 100 g−1· min−1). No significant difference in mean CBF was observed between both anesthetics at identical MAC levels. The increase in CBF observed for the whole brain was also evident from the local values. LCBF was increased in all of the 40 brain structures investigated during anesthesia, except for in the auditory cortex in which LCBF was reduced at an increasing anesthetic depth. At 1 MAC isoflurane and desflurane, a close coupling between blood flow and metabolism could be seen for all 40 brain structures analyzed (fig. 1). At 2 MAC, coupling was mainly preserved. The lower correlation coefficients observed at 2 MAC compared with 1 MAC were because of the finding that, in some brain regions, metabolism was not or was only slightly decreased during either isoflurane or desflurane anesthesia.
Fig. 1. Coupling of local cerebral blood flow (LCBF) to local cerebral glucose utilization (LCGU) in 40 brain structures during 1 and 2 MAC isoflurane anesthesia (  bottom  ) and desflurane anesthesia (  top  ) compared with conscious control rats (n = 6 for each LCGU value and each LCBF value at all MAC levels). The regression lines were calculated according to y = ax + b, where y is LCBF and x is LCGU. Control: y = 1.5 x + 4.9; isoflurane 1 MAC: y = 2.6 x + 42.2; isoflurane 2 MAC: y = 2.1 x + 116; desflurane 1 MAC: y = 3.5 x + 32.1; desflurane 2 MAC: y = 3.2 x + 98.4. 
Fig. 1. Coupling of local cerebral blood flow (LCBF) to local cerebral glucose utilization (LCGU) in 40 brain structures during 1 and 2 MAC isoflurane anesthesia (  bottom  ) and desflurane anesthesia (  top  ) compared with conscious control rats (n = 6 for each LCGU value and each LCBF value at all MAC levels). The regression lines were calculated according to y = ax + b, where y is LCBF and x is LCGU. Control: y = 1.5 x + 4.9; isoflurane 1 MAC: y = 2.6 x + 42.2; isoflurane 2 MAC: y = 2.1 x + 116; desflurane 1 MAC: y = 3.5 x + 32.1; desflurane 2 MAC: y = 3.2 x + 98.4. 
Fig. 1. Coupling of local cerebral blood flow (LCBF) to local cerebral glucose utilization (LCGU) in 40 brain structures during 1 and 2 MAC isoflurane anesthesia (  bottom  ) and desflurane anesthesia (  top  ) compared with conscious control rats (n = 6 for each LCGU value and each LCBF value at all MAC levels). The regression lines were calculated according to y = ax + b, where y is LCBF and x is LCGU. Control: y = 1.5 x + 4.9; isoflurane 1 MAC: y = 2.6 x + 42.2; isoflurane 2 MAC: y = 2.1 x + 116; desflurane 1 MAC: y = 3.5 x + 32.1; desflurane 2 MAC: y = 3.2 x + 98.4. 
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Discussion 
This study extends our previous work regarding isoflurane and sevoflurane anesthesia. 1 The decrease of mean CGU observed in rats during 1 MAC and 2 MAC desflurane anesthesia (52 to 62%) was similar to that obtained during sevoflurane (34 to 59%)1 anesthesia. Lutz et al.  11 measured a smaller decrease in the metabolic rate of oxygen (26%) in dogs, when the end-tidal concentration of desflurane was increased from 0.5 MAC to 2.0 MAC. 11 This difference may be explained by the light anesthesia of the control group in the study of Lutz et al.  , 11 decreasing baseline values of metabolic rate of oxygen, whereas conscious animals were used as controls in the current investigation. LCGU during desflurane anesthesia showed a more uniform decrease in the current study compared with the metabolic effects observed during sevoflurane anesthesia 1 and other anesthetics analyzed previously. 6,12–22 Whereas the increase of mean CBF during sevoflurane anesthesia was significantly lower at 2 MAC than the increase during isoflurane anesthesia, 1 no differences in mean CBF could be found between isoflurane and desflurane at both MAC levels investigated. Few other studies have described CBF during desflurane anesthesia. 11,23–25 An increase in the end-tidal concentration of desflurane from 0.5 MAC to 2 MAC induced an increase in CBF by 43% when mean arterial pressure was maintained by infusion of phenylephrine in dogs. 11 The smaller change in CBF compared with the finding in rats (+68%)1 may again be explained by the slight anesthesia used for control measurements by Lutz et al.  11 In humans, no difference in CBF could be observed between desflurane and isoflurane anesthesia at an end-tidal concentration of 1.25 MAC and a partial pressure of arterial carbon dioxide (PaCO2) of 35 mmHg. 25 This finding in humans is in accordance with that of the current study in rats. Local analysis of blood flow in the current study showed that LCBF was moderately reduced in the auditory cortex during desflurane and isoflurane anesthesia, in contrast to all other brain structures in which LCBF was increased. The decrease of LCBF in auditory cortex was paralleled by the largest reduction of LCGU measured among all cortical structures (desflurane, −80%; isoflurane, −82% at 2 MAC). If blood flow is coupled to metabolism on a local level, the reduction of LCBF could therefore be explained by the decreased metabolic demand of the tissue that is not completely compensated for by vasodilative effects of the volatile anesthetics in the auditory cortex. The current investigation shows that the local coupling between LCGU and LCBF found during conscious control conditions 26 is preserved during anesthesia induced by 1 MAC desflurane or isoflurane, although the relation is reset to higher levels of blood flow. During 2 MAC desflurane and isoflurane anesthesia, some brain structures in which no or only slight decreases in the metabolic rate could be measured during anesthesia seemed to deviate from this pattern. These results confirm observations from previous coupling studies of Hansen et al.  7 for 1 MAC halothane and isoflurane, Maekawa et al.  6 for 1 and 2 MAC isoflurane, and our own findings during sevoflurane anesthesia at 1 and 2 MAC. 1 During 1 MAC isoflurane anesthesia, in all three studies, coupling parameters can be found in similar ranges (Maekawa et al.  6 : r = 0.82; LCBF = 2.2 × LCGU + 67 [calculated from published data 6 ]; Hansen et al.  7 : r = 0.78; LCBF = 1.9 × LCGU + 47; the current investigation: r = 0.87; LCBF = 2.6 × LCGU + 42). In contrast, during 2 MAC isoflurane anesthesia, a lower correlation between LCBF and LCGU values is observed (Maekawa et al.  6 : r = 0.45; LCBF = 2.6 × LCGU + 208; the current investigation: r = 0.68; LCBF = 2.4 × LCGU + 99). 1,6,7 In conclusion, the current investigation shows that desflurane induces a decrease of global glucose use and an increase of global blood flow in the brain that are comparable to those induced by isoflurane. The local analysis reveals a slightly more uniform decrease of LCGU during desflurane than during isoflurane anesthesia. Finally, the correlation (coupling) between LCGU and LCBF is reset during desflurane and isoflurane anesthesia, although it is preserved at 1 MAC and to a lesser extent at 2 MAC during desflurane anesthesia.
References 
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Fig. 1. Coupling of local cerebral blood flow (LCBF) to local cerebral glucose utilization (LCGU) in 40 brain structures during 1 and 2 MAC isoflurane anesthesia (  bottom  ) and desflurane anesthesia (  top  ) compared with conscious control rats (n = 6 for each LCGU value and each LCBF value at all MAC levels). The regression lines were calculated according to y = ax + b, where y is LCBF and x is LCGU. Control: y = 1.5 x + 4.9; isoflurane 1 MAC: y = 2.6 x + 42.2; isoflurane 2 MAC: y = 2.1 x + 116; desflurane 1 MAC: y = 3.5 x + 32.1; desflurane 2 MAC: y = 3.2 x + 98.4. 
Fig. 1. Coupling of local cerebral blood flow (LCBF) to local cerebral glucose utilization (LCGU) in 40 brain structures during 1 and 2 MAC isoflurane anesthesia (  bottom  ) and desflurane anesthesia (  top  ) compared with conscious control rats (n = 6 for each LCGU value and each LCBF value at all MAC levels). The regression lines were calculated according to y = ax + b, where y is LCBF and x is LCGU. Control: y = 1.5 x + 4.9; isoflurane 1 MAC: y = 2.6 x + 42.2; isoflurane 2 MAC: y = 2.1 x + 116; desflurane 1 MAC: y = 3.5 x + 32.1; desflurane 2 MAC: y = 3.2 x + 98.4. 
Fig. 1. Coupling of local cerebral blood flow (LCBF) to local cerebral glucose utilization (LCGU) in 40 brain structures during 1 and 2 MAC isoflurane anesthesia (  bottom  ) and desflurane anesthesia (  top  ) compared with conscious control rats (n = 6 for each LCGU value and each LCBF value at all MAC levels). The regression lines were calculated according to y = ax + b, where y is LCBF and x is LCGU. Control: y = 1.5 x + 4.9; isoflurane 1 MAC: y = 2.6 x + 42.2; isoflurane 2 MAC: y = 2.1 x + 116; desflurane 1 MAC: y = 3.5 x + 32.1; desflurane 2 MAC: y = 3.2 x + 98.4. 
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