Anesthetic preconditioning: triggering role of reactive oxygen and nitrogen species in isolated hearts

We postulated that anesthetic preconditioning (APC) is triggered by reactive oxygen/nitrogen species (ROS/RNS). We used the isolated guinea pig heart perfused with L-tyrosine, which reacts with ROS and RNS to form strong oxidants, principally peroxynitrite (ONOO-), and then forms fluorescent dityrosine. ROS scavengers superoxide dismutase, catalase, and glutathione (SCG) and NO. synthesis inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) were given 5 min before and after sevoflurane preconditioning stimuli. Drugs were washed out before 30 min of ischemia and 120 min of reperfusion. Groups were control (nontreated ischemia control), APC (two, 2-min periods of perfusion with 0.32 +/- 0.02 mM of sevoflurane; separated by a 6-min period of perfusion without sevoflurane), SCG, APC + SCG, L-NAME, and APC + L-NAME. Effluent dityrosine at 1 min reperfusion was 56 +/- 6 (SE)double dagger, 15 +/- 5, 40 +/- 5double dagger, 39 +/- 4double dagger, 35 +/- 4double dagger, and 33 +/- 5double dagger units (double dagger P < 0.05 vs. APC), respectively; left ventricular pressure (% baseline) at 60 min of reperfusion was 30 +/- 5&DDAG;, 60 +/- 4, 35 +/- 5&DDAG;, 37 +/- 5&DDAG;, 44 +/- 4, and 47 +/- 4; and infarct size (% total heart weight) was 50 +/- 5&DDAG;, 19 +/- 2, 48 +/- 3&DDAG;, 46 +/- 4&DDAG;, 42 +/- 4&DDAG;, and 45 +/- 2&DDAG;. Thus APC is initiated by ROS as shown by improved function, reduced infarct size, and reduced dityrosine on reperfusion; protective and ROS/RNS-reducing effect of APC were attenuated when bracketed by ROS scavengers or NO• inhibition.