N-acetylcysteine restores isoflurane-induced preconditioning against myocardial infarction during hyperglycemia.
BACKGROUND
Hyperglycemia generates reactive oxygen species and prevents isoflurane-induced preconditioning. The authors tested the hypothesis that scavenging reactive oxygen species with N-acetylcysteine will restore protection against myocardial infarction produced by isoflurane in vivo.


METHODS
Barbiturate-anesthetized dogs (n = 45) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size and coronary collateral blood flow were measured with triphenyltetrazolium staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of 0.9% saline or 15% dextrose in water to increase blood glucose concentrations to 600 mg/dl (hyperglycemia) in the absence or presence of isoflurane (1.0 minimum alveolar concentration) with or without pretreatment with N-acetylcysteine (150 mg/kg i.v.) in six experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion.


RESULTS
Myocardial infarct size was 27 +/- 2% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%; n = 7). Hyperglycemia alone did not alter infarct size (29 +/- 3%; n = 7) but abolished the protective effect of isoflurane (25 +/- 2%; n = 8). N-Acetylcysteine alone did not affect infarct size (28 +/- 2%; n = 8) but restored isoflurane-induced cardioprotection during hyperglycemia (10 +/- 1%; n = 7).


CONCLUSIONS
Acute hyperglycemia abolishes reductions in myocardial infarct size produced by isoflurane, but N-acetylcysteine restores these beneficial effects. The results suggest that excessive quantities of reactive oxygen species generated during hyperglycemia impair isoflurane-induced preconditioning in dogs.
Kehl
Franz
F
Department of Anesthesiology, Medical College of Wisconsin and the Zablocki VA Medical Center, Milwaukee, Wisconsin 53226, USA.
Krolikowski
John G
JG
Weihrauch
Dorothee
D
Pagel
Paul S
PS
Warltier
David C
DC
Kersten
Judy R
JR
D000111:Acetylcysteine / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D016277:Ventricular Function, Left / Q000187:drug effects
D018685:Anesthetics, Inhalation; D016166:Free Radical Scavengers; D007530:Isoflurane; D000111:Acetylcysteine