Faculty Collaboration Database

Sevoflurane reduces myocardial infarct size and decreases the time threshold for ischemic preconditioning in dogs. Anesthesiology 1999 Nov;91(5):1437-46

Date

11/07/1999

Pubmed ID

10551596

DOI

10.1097/00000542-199911000-00037

Scopus ID

2-s2.0-0032730076 (requires institutional sign-in at Scopus site)   159 Citations

Abstract

BACKGROUND: Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (K(ATP)) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction.

METHODS: Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the K(ATP) channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

RESULTS: Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%).

CONCLUSION: Sevoflurane reduces myocardial infarct size by activating K(ATP) channels and reduces the time threshold for ischemic preconditioning independent of hemodynamic effects in vivo.

Author List

Toller WG, Kersten JR, Pagel PS, Hettrick DA, Warltier DC

Authors

Paul S. Pagel PhD, MS, MD Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin
David C. Warltier PhD Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

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

Adenosine Triphosphate
Anesthetics, Inhalation
Animals
Blood Pressure
Coronary Circulation
Dogs
Female
Glyburide
Hemodynamics
Ischemic Preconditioning, Myocardial
Male
Methyl Ethers
Myocardial Infarction
Potassium Channels
Time Factors