Faculty Collaboration Database

Sevoflurane preconditioning before moderate hypothermic ischemia protects against cytosolic [Ca(2+)] loading and myocardial damage in part via mitochondrial K(ATP) channels. Anesthesiology 2002 Oct;97(4):912-20

Date

10/03/2002

Pubmed ID

12357159

DOI

10.1097/00000542-200210000-00025

Scopus ID

2-s2.0-0036791293 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

BACKGROUND: Brief sevoflurane exposure and washout (sevoflurane preconditioning [SPC]) before 30-min global ischemia at 37 degrees C is known to improve cardiac function, decrease cytosolic [Ca(2+)] loading, and reduce infarct size on reperfusion. It is not known if anesthetic preconditioning (APC) applies as well to hypothermic ischemia and reperfusion and if K(ATP) channels are involved. The authors examined in guinea pig isolated hearts the effect of sevoflurane exposure before 4-h global ischemia at 17 degrees C on cardiac function, cytosolic [Ca(2+)] loading, and infarct size. In addition they tested the potential role of the mitochondrial K(ATP) channel in eliciting the cardioprotection by SPC.

METHODS: Hearts were randomly assigned to (1) a nontreated hypothermic ischemia group (CON), (2) a group given 3.5 vol% sevoflurane for 15 min with a 15-min washout before hypothermic ischemia (SPC), and (3) an SPC group in which anesthetic exposure was bracketed with 200 microm 5-hydroxydecanoate (5-HD) from 5 min before until 5 min after sevoflurane (SPC + 5-HD). Cytosolic [Ca(2+)] was measured in the left ventricular (LV) free wall with the intracellularly loaded fluorescence probe indo-1.

RESULTS: Initial reperfusion in CON hearts markedly increased systolic and diastolic [Ca(2+)] and reduced contractility (dLVP/dt(max)), relaxation (diastolic LVP, dLVP/dt(min)), myocardial oxygen consumption (MvO(2)), and cardiac efficiency. In SPC hearts, cytosolic [Ca(2+)] overloading (especially diastolic [Ca(2+)]) was decreased with increased myocardial [Ca(2+)] influx (d[Ca(2+)]/dt(max)) and efflux (d[Ca(2+)]/dt(min)), improved contractility, relaxation, coronary flow, MvO(2), cardiac efficiency, and decreased infarct size. In SPC + 5HD hearts, the reduction in infarct size was antagonized by 5-HD, but functional return was less affected by 5-HD.

CONCLUSIONS: Anesthetic preconditioning occurs after long-term hypothermic ischemia, and the infarct size reduction is the result, in part, of mitochondrial K(ATP) channel opening.

Author List

Chen Q, Camara AK, An J, Novalija E, Riess ML, Stowe DF

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
David F. Stowe PhD, MA, MA Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

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

ATP-Binding Cassette Transporters
Anesthetics, Inhalation
Animals
Calcium
Coronary Circulation
Creatine Kinase
Cytosol
Guinea Pigs
Heart Rate
Hypothermia, Induced
In Vitro Techniques
Ischemic Preconditioning
KATP Channels
Methyl Ethers
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Oxygen Consumption
Potassium Channels
Potassium Channels, Inwardly Rectifying
Ventricular Function, Left