title: Is isoflurane-induced preconditioning dose related?
abstract: BACKGROUND
  Volatile anesthetics precondition against myocardial infarction, but it is unknown whether this beneficial action is threshold- or dose-dependent. The authors tested the hypothesis that isoflurane decreases myocardial infarct size in a dose-dependent fashion in vivo.
  
  
  METHODS
  Barbiturate-anesthetized dogs (n = 40) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular pressures and rate of increase of left ventricular pressure. Dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive either 0.0, 0.25, 0.5, 1.0, or 1.25 minimum alveolar concentration (MAC) isoflurane in separate groups. Isoflurane was administered for 30 min and discontinued 30 min before left anterior descending coronary artery occlusion.
  
  
  RESULTS
  Infarct size (triphenyltetrazolium staining) was 29 +/- 2% of the area at risk in control experiments (0.0 MAC). Isoflurane produced significant (P < 0.05) reductions of infarct size (17 +/- 3, 13 +/- 1, 14 +/- 2, and 11 +/- 1% of the area at risk during 0.25, 0.5, 1.0, and 1.25 MAC, respectively). Infarct size was inversely related to coronary collateral blood flow (radioactive microspheres) in control experiments and during low (0.25 or 0.5 MAC) but not higher concentrations of isoflurane. Isoflurane shifted the linear regression relation between infarct size and collateral perfusion downward (indicating cardioprotection) in a dose-dependent fashion.
  
  
  CONCLUSIONS
  Concentrations of isoflurane as low as 0.25 MAC are sufficient to precondition myocardium against infarction. High concentrations of isoflurane may have greater efficacy to protect myocardium during conditions of low coronary collateral blood flow.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin and the Zablocki VA Medical Center, Milwaukee, Wisconsin 53226, USA.
authors.forename: Franz
authors.initials: F
authors.lastname: Kehl
authors.forename: John G
authors.initials: JG
authors.lastname: Krolikowski
authors.forename: Boris
authors.initials: B
authors.lastname: Mraovic
authors.forename: Paul S
authors.initials: PS
authors.lastname: Pagel
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; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D010477:Perfusion
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane