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

Abstract

We postulated that anesthetic preconditioning (APC) is triggered by reactive oxygen/nitrogen species (ROS/RNS). We used the isolated guinea pig heart perfused withl-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)‡, 15 ± 5, 40 ± 5‡, 39 ± 4‡, 35 ± 4‡, and 33 ± 5‡ units (‡ P < 0.05 vs. APC), respectively; left ventricular pressure (%baseline) at 60 min of reperfusion was 30 ± 5‡, 60 ± 4, 35 ± 5‡, 37 ± 5‡, 44 ± 4, and 47 ± 4; and infarct size (%total heart weight) was 50 ± 5‡, 19 ± 2, 48 ± 3‡, 46 ± 4‡, 42 ± 4‡, and 45 ± 2‡. 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.