title: Isoflurane does not produce a second window of preconditioning against myocardial infarction in vivo.
abstract: The administration of a volatile anesthetic shortly before a prolonged ischemic episode exerts protective effects against myocardial infarction similar to those of ischemic preconditioning. A second window of preconditioning (SWOP) against myocardial infarction can also be elicited by brief episodes of ischemia when this occurs 24 h before prolonged coronary artery occlusion. Whether remote exposure to a volatile anesthetic also causes delayed myocardial protection is unknown. We tested the hypothesis that the administration of isoflurane 24 h before ischemia produces a SWOP against infarction. Barbiturate-anesthetized dogs (n = 25) were instrumented for measurement of hemodynamics, including aortic and left ventricular (LV) pressures and LV +dP/dt(max), and subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and coronary collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Two groups of dogs received 1.0 minimum alveolar anesthetic concentration isoflurane for 30 min or 6 h that was discontinued 30 min (acute) or 24 h (delayed) before ischemia and reperfusion, respectively. A control group of dogs did not receive isoflurane. Infarct size was 27% +/- 3% of the LV area at risk in the absence of pretreatment with isoflurane. Acute, but not remote, administration of isoflurane reduced infarct size (12% +/- 1% and 31% +/- 3%, respectively). No differences in hemodynamics or transmural myocardial perfusion during or after occlusion were observed between groups. The results indicate that isoflurane does not produce a SWOP when administered 24 h before prolonged myocardial ischemia in vivo.
  
  
  CONCLUSIONS
  Isoflurane mimics the beneficial effects of ischemic preconditioning by protecting myocardium against infarction when it is administered shortly before a prolonged ischemic episode. However, unlike ischemic preconditioning, isoflurane does not produce a second window of protection 24 h after administration in dogs.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Franz
authors.initials: F
authors.lastname: Kehl
authors.forename: Paul S
authors.initials: PS
authors.lastname: Pagel
authors.forename: John G
authors.initials: JG
authors.lastname: Krolikowski
authors.forename: Weidong
authors.initials: W
authors.lastname: Gu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Toller
authors.forename: David C
authors.initials: DC
authors.lastname: Warltier
authors.forename: Judy R
authors.initials: JR
authors.lastname: Kersten
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002138:Calibration; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D011877:Radionuclide Imaging
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane