Acute ethanol exposure fails to elicit preconditioning-like protection in in situ rabbit hearts because of its continued presence during ischemia

OBJECTIVES Is the timing of exposure critical for ethanol's ability to indu ce cardioprotection? BACKGROUND Acute ethanol exposure has been reported to mimic ischemic preco nditioning in vitro, but it failed to protect in situ. We hypothesized that these conflicting findings were related to ethanol's presence during ische mia 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 m easured in open-chest rabbits after 30 min of regional ischemia and reperfu sion and was compared to ethanol's ability to reduce infarct size in isolat ed hearts in which the timing of ethanol exposure could be varied. RESULTS Ethanol exposure in situ shortly before ischemia did not reduce inf arct size. Moreover, ethanol abolished protection from both ischemic precon ditioning and mitochondrial K-ATP channel activation. In contrast, in buffe r-perfused hearts exposed to 10 to 50 mmol/liter ethanol for 5 min followed by washout before ischemia, infarct size was significantly reduced. When e thanol 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 ethano l-free buffer prior to ischemia in a Langendorff preparation. When 50 min w ere allowed to metabolize the ethanol prior to ischemia, protection could a lso be shown in situ. CONCLUSIONS Ethanol exposure followed by washout or sufficient time to meta bolize the alcohol prior to ischemia induces preconditioning-like myocardia l protection. However, if present throughout ischemia, ethanol actually blo cks all preconditioning-related protection. (C) 2001 by the American Colleg e of Cardiology.