title: Preconditioning by isoflurane retains its protection against ischemia-reperfusion injury in postinfarct remodeled rat hearts.
abstract: BACKGROUND
  Postinfarct remodeling in the heart may affect protective signaling. We tested whether isoflurane preconditioning retains its protection in postinfarct remodeled hearts.
  
  
  METHODS
  Myocardial remodeling was induced by ligation of the left anterior descending coronary artery in male Wistar rats. Six weeks later, diseased hearts were mounted on a Langendorff apparatus and exposed to 40 min of ischemia followed by 90 min of reperfusion. Isoflurane preconditioning was induced with 1.5 MAC (2.1 vol%) isoflurane for 15 min. Infarct size was determined using 1% triphenyltetrazolium chloride staining and corroborated with measurements of lactate dehydrogenase (LDH) release into the perfusate. In some experiments, the protein kinase B and mitochondrial ATP-dependent potassium channel inhibitors LY294002 (10 microM) or 5-hydroxydecanoate (100 microM), respectively, were concomitantly added with isoflurane. Cardiac function was recorded.
  
  
  RESULTS
  Six weeks after permanent coronary artery ligation, infarct rats exhibited a markedly increased heart weight/body weight index (5.41 +/- 0.64 vs 3.60 +/- 0.59 g/kg, P < 0.0001) confirming remodeling with compensatory hypertrophy. Isoflurane preconditioning decreased LDH release and reduced infarct size from 32% +/- 6% to 2% +/- 2% (P < 0.0001). Concomitant administration of LY294002 or 5-hydroxydecanoate with isoflurane completely abolished this protection. Functional assessment also showed significant protection from postischemic stunning by isoflurane preconditioning in remodeled hearts, which was lost in the presence of both blockers.
  
  
  CONCLUSIONS
  Myocardial preconditioning with isoflurane retains its protection against ischemia/reperfusion injury in postinfarct remodeled rat hearts via similar signaling pathways, as previously reported in healthy hearts.
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Switzerland.
authors.forename: Eliana
authors.initials: E
authors.lastname: Lucchinetti
authors.forename: Marina
authors.initials: M
authors.lastname: Jamnicki
authors.forename: Gregor
authors.initials: G
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Zaugg
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002867:Chromones / Q000494:pharmacology; D003331:Coronary Vessels / Q000601:surgery; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D006880:Hydroxy Acids / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology* / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008026:Ligation; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D002867:Chromones; D003652:Decanoic Acids; D006880:Hydroxy Acids; D009025:Morpholines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; C117780:mitochondrial K(ATP) channel; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C052853:5-hydroxydecanoic acid; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt