title: Acute ethanol exposure fails to elicit preconditioning-like protection in in situ rabbit hearts because of its continued presence during ischemia.
abstract: OBJECTIVE
  Is the timing of exposure critical for ethanol's ability to induce cardioprotection?
  
  
  BACKGROUND
  Acute ethanol exposure has been reported to mimic ischemic preconditioning in vitro, but it failed to protect in situ. We hypothesized that these conflicting findings were related to ethanol's presence during ischemia in situ.
  
  
  METHODS
  The effect on infarct size (triphenyltetrazolium chloride) of acute ethanol exposure (0.35, 0.7, and 1.4 g/kg IV) 10 min before ischemia was measured in open-chest rabbits after 30 min of regional ischemia and reperfusion and was compared to ethanol's ability to reduce infarct size in isolated hearts in which the timing of ethanol exposure could be varied.
  
  
  RESULTS
  Ethanol exposure in situ shortly before ischemia did not reduce infarct size. Moreover, ethanol abolished protection from both ischemic preconditioning and mitochondrial KATP channel activation. In contrast, in buffer-perfused hearts exposed to 10 to 50 mmol/liter ethanol for 5 min followed by washout before ischemia, infarct size was significantly reduced. When ethanol exposure was prolonged until the end of ischemia in isolated hearts, protection was abolished. Conversely, protection was seen when ethanol was infused in situ followed by removal of the heart and perfusion with ethanol-free buffer prior to ischemia in a Langendorff preparation. When 50 min were allowed to metabolize the ethanol prior to ischemia, protection could also be shown in situ.
  
  
  CONCLUSIONS
  Ethanol exposure followed by washout or sufficient time to metabolize the alcohol prior to ischemia induces preconditioning-like myocardial protection. However, if present throughout ischemia, ethanol actually blocks all preconditioning-related protection.
authors.affiliation: Department of Physiology, University of South Alabama, Mobile 36688, USA.
authors.forename: M
authors.initials: M
authors.lastname: Krenz
authors.forename: C P
authors.initials: CP
authors.lastname: Baines
authors.forename: X M
authors.initials: XM
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Heusch
authors.forename: M V
authors.initials: MV
authors.lastname: Cohen
authors.forename: J M
authors.initials: JM
authors.lastname: Downey
mesh_terms: D000818:Animals; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits
chemical_list: D000431:Ethanol