title: Isoflurane delays but does not prevent cerebral infarction in rats subjected to focal ischemia.
abstract: BACKGROUND
  Several investigations have shown that volatile anesthetics can reduce ischemic cerebral injury. In these studies, however, neurologic injury was evaluated only after a short recovery period. Recent data suggest that injury caused by ischemia is a dynamic process characterized by continual neuronal loss for a prolonged period. Whether isoflurane-mediated neuroprotection is sustained after a longer recovery period is not known. The current study was conducted to compare the effect of isoflurane on brain injury after short (2-day) and long (14-day) recovery periods in rats subjected to focal ischemia.
  
  
  METHODS
  Fasted Wistar-Kyoto rats were anesthetized with isoflurane and randomly allocated to an awake (n = 36) or an isoflurane (n = 34) group. Animals in both groups were subjected to focal ischemia by filament occlusion of the middle cerebral artery. Pericranial temperature was servocontrolled at 37 degrees C throughout the experiment. In the awake group, isoflurane was discontinued and the animals were allowed to awaken. In the isoflurane group, isoflurane anesthesia was maintained at 1.5 times the minimum alveolar concentration. After 70 min of focal ischemia, the filament was removed. Animals were killed 2 days (awake, n = 18; isoflurane, n = 17) and 14 days (awake, n = 18; isoflurane, n = 17) after ischemia. The volumes of cerebral infarction and selective neuronal necrosis in the animals were determined by image analysis of hematoxylin and eosin-stained coronal brain sections.
  
  
  RESULTS
  Cortical and subcortical volumes of infarction were significantly less in the isoflurane 2-day group (26 +/- 23 mm3 and 17 +/- 6 mm3, respectively) than in the awake 2-day group (58 +/- 35 mm3, P < 0. 01; and 28 +/- 12 mm3, P < 0.01, respectively). By contrast, cortical and subcortical volumes of infarction in the awake (41 +/- 31 mm3 and 28 +/- 16 mm3, respectively) and isoflurane (41 +/- 35 mm3 and 19 +/- 8 mm3, respectively) 14-day groups were not different (cortex, P = 0.99; subcortex, P = 0.08). The volume of cortical tissue in which selective neuronal necrosis was observed, however, was significantly less in the isoflurane 14-day group (5 +/- 4 mm3) than in the awake 14-day group (17 +/- 9 mm3, P < 0.01). The total number of necrotic neurons in the region of selective neuronal necrosis was significantly smaller in the isoflurane 14-day group than in the awake 14-day group (P < 0.01).
  
  
  CONCLUSIONS
  Compared with the awake state, isoflurane reduced the extent of infarction assessed 2 days after focal ischemia in rats. At 14 days, however, only selective neuronal necrosis, but not infarction, was reduced by isoflurane. These results suggest that isoflurane delays but does not prevent cerebral infarction caused by focal ischemia. Isoflurane may attenuate the delayed development of selective neuronal necrosis in periinfarct areas in this animal model.
authors.affiliation: Department of Anesthesiology, VA Medical Center and University of California, San Diego, California 92161, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: J R
authors.initials: JR
authors.lastname: Kimbro
authors.forename: J C
authors.initials: JC
authors.lastname: Drummond
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
authors.forename: P J
authors.initials: PJ
authors.lastname: Kelly
authors.forename: P M
authors.initials: PM
authors.lastname: Patel
mesh_terms: D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D007530:Isoflurane