Faculty Collaboration Database

N-acetylcysteine restores isoflurane-induced preconditioning against myocardial infarction during hyperglycemia. Anesthesiology 2003 Jun;98(6):1384-90

Date

05/27/2003

Pubmed ID

12766647

DOI

10.1097/00000542-200306000-00013

Scopus ID

2-s2.0-0038443952 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

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.

Author List

Kehl F, Krolikowski JG, Weihrauch D, Pagel PS, Warltier DC, Kersten JR

Author

Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Anesthetics, Inhalation
Animals
Collateral Circulation
Coronary Circulation
Dogs
Female
Free Radical Scavengers
Hemodynamics
Hyperglycemia
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Myocardial Infarction
Myocardium
Ventricular Function, Left