title: Ischemic but not pharmacological preconditioning requires protein synthesis.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) and pharmacological preconditioning (PPC) have both been shown to confer cardioprotective effects. However, the role of protein synthesis in preconditioning is unclear.
  
  
  RESULTS
  Isolated rabbit hearts were treated with cycloheximide (CHx, 10 micromol/L), a protein synthesis inhibitor at the translational level, before 2 cycles of IPC (5 minutes of global ischemia/5 minutes of reperfusion, n=6) or PPC by pinacidil (PIN, 10 micromol/L; n=6), an ATP-sensitive potassium channel opener. Six rabbit hearts received actinomycin D (Act D, 20 micromol/L; n=6), a protein synthesis inhibitor at the transcriptional level, before IPC. The left anterior descending coronary artery was then occluded for 60 minutes and reperfused for 120 minutes. Control hearts received no treatment before prolonged ischemia (n=6). Left ventricular pressure, action potential duration, and coronary flow were measured. Infarct size is expressed as a percentage of the area at risk. IPC (n=6) and PIN (n=8) hearts experienced reduced infarct size compared with control hearts (22+/-3% and 27+/-2% versus 46+/-3%, IPC and PIN versus control; P:<0.01). Translational blockade (CHx) reversed the IPC infarct size reduction effect (22+/-3% versus 48+/-4%, IPC versus CHx+IPC; P:<0.01) but not the effects of pinacidil (27+/-2% versus 29+/-3%, PIN versus CHx+PIN; P:=NS). Transcriptional blockade (Act D) did not abolish the IPC effect (23+/-5% versus 22+/-3%, Act D+IPC versus IPC; P:=NS). There were no significant differences in electromechanical function consequent to CHx and Act D treatment.
  
  
  CONCLUSIONS
  These findings suggest an important role for protein synthesis in the mechanism for IPC-mediated protection at the translational level, which may be different from PPC.
authors.affiliation: Division of Cardiothoracic Surgery, The Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: N
authors.initials: N
authors.lastname: Matsuyama
authors.forename: J E
authors.initials: JE
authors.lastname: Leavens
authors.forename: D
authors.initials: D
authors.lastname: McKinnon
authors.forename: G R
authors.initials: GR
authors.lastname: Gaudette
authors.forename: T O
authors.initials: TO
authors.lastname: Aksehirli
authors.forename: I B
authors.initials: IB
authors.lastname: Krukenkamp
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D020110:Pinacidil; D003513:Cycloheximide