Isoflurane preconditions myocardium against infarction via activation of inhibitory guanine nucleotide binding proteins

Background: Isoflurane-induced myocardial protection during ischemia is med iated by adenosine triphosphate-regulated potassium (K-ATP) channels; howev er, the intracellular signal transduction cascade responsible for this proc ess has been incompletely evaluated. The authors tested the hypothesis that isoflurane reduces myocardial infarct size through a G(i) protein-mediated process. Methods: Forty-eight hours after pretreatment with vehicle (0.9% saline) or the G(i) protein inhibitor pertussis toxin (10 mu g/kg intravenously), bar biturate-anesthetized dogs (n = 43) were instrumented for measurement of ao rtic and left ventricular pressures and maximum rate of increase of left ve ntricular pressure. All dogs were subjected to a 60-min left anterior desce nding coronary artery occlusion followed by 3-h K-perfusion. In four separa te groups, vehicle- or pertussis toxin-pre-treated dogs were studied with o r without administration of 1 minimum alveolar concentration isoflurane. In two additional groups, dogs: received the direct K-ATP channel agonist nic orandil (100 mu g/kg bolus and 10 mu g . kg(-1) . min(-1) intravenous infus ion) in the presence or absence of pertussis toxin pretreatment, Myocardial perfusion and Infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results: Isoflurane significantly (P < 0.05) decreased infarct size to 7 +/ - 2% of the area at risk compared with control experiments (26 +/- 2%). Per tussis toxin pretreatment alone had no effects on myocardial infarct size ( 31 +/- 4%) but blocked the beneficial effects of isoflurane (21 +/- 3%). Ni corandil decreased infarct size (11 +/- 2%), but, in contrast to isoflurane , this effect was independent of pertussis toxin pretreatment (11 +/- 1%). Conclusion: Isoflurane reduces myocardial infarct size by a G(i) protein-me diated mechanism in vivo.