Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species.
BACKGROUND
Reactive oxygen species (ROS) contribute to myocardial protection during ischemic preconditioning, but the role of the ROS in protection against ischemic injury produced by volatile anesthetics has only recently been explored. We tested the hypothesis that ROS mediate isoflurane-induced preconditioning in vivo.


METHODS
Pentobarbital-anesthetized rabbits were instrumented for measurement of hemodynamics and were subjected to a 30 min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive vehicle (0.9% saline), or the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptopropionyl glycine (2-MPG; 1 mg. kg(-1).min(-1)), in the presence or absence of 1.0 minimum alveolar concentration (MAC) isoflurane. Isoflurane was administered for 30 min and then discontinued 15 min before coronary artery occlusion. A fluorescent probe for superoxide anion production (dihydroethidium, 2 mg) was administered in the absence of the volatile anesthetic or 5 min before exposure to isoflurane in 2 additional groups (n = 8). Myocardial infarct size and superoxide anion production were assessed using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively.


RESULTS
Isoflurane (P < 0.05) decreased infarct size to 24 +/- 4% (mean +/- SEM; n = 10) of the left ventricular area at risk compared with control experiments (43 +/- 3%; n = 8). NAC (43 +/- 3%; n = 7) and 2-MPG (42 +/- 5%; n = 8) abolished this beneficial effect, but had no effect on myocardial infarct size (47 +/- 3%; n = 8 and 46 +/- 3; n = 7, respectively) when administered alone. Isoflurane increased superoxide anion production as compared with control experiments (28 +/- 12 -6 +/- 9 fluorescence units; P < 0.05).


CONCLUSIONS
The results indicate that ROS produced following administration of isoflurane contribute to protection against myocardial infarction in vivo.
Tanaka
Katsuya
K
Department of Anesthesiology, Pharmacology and Toxicology, the Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Weihrauch
Dorothee
D
Kehl
Franz
F
Ludwig
Lynda M
LM
LaDisa
John F
JF
Kersten
Judy R
JR
Pagel
Paul S
PS
Warltier
David C
DC
D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000627:therapeutic use*
D018685:Anesthetics, Inhalation; D017382:Reactive Oxygen Species; D007530:Isoflurane