title: Isoflurane preconditions myocardium against infarction via release of free radicals.
abstract: BACKGROUND
  Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals.
  
  
  METHODS
  Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7).
  
  
  RESULTS
  Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001).
  
  
  CONCLUSIONS
  Isoflurane-induced preconditioning depends on the release of free radicals.
authors.affiliation: Klinik für Anaesthesiologie and Institut für Herz- und Kreislaufphysiologie, Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Jost
authors.initials: J
authors.lastname: Müllenheim
authors.forename: Dirk
authors.initials: D
authors.lastname: Ebel
authors.forename: Jan
authors.initials: J
authors.lastname: Frässdorf
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.forename: Volker
authors.initials: V
authors.lastname: Thämer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlack
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D005609:Free Radicals; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology; D009203:Myocardial Infarction / Q000517:prevention & control*; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D005609:Free Radicals; D008665:Metalloporphyrins; C110658:N-(2-mercaptoproprionyl)-glycine; D013438:Sulfhydryl Compounds; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D007530:Isoflurane; D005998:Glycine