Sevoflurane Preconditioning before Moderate Hypothermic Ischemia Protects against Cytosolic [Ca2+] Loading and Myocardial Damage in Part via Mitochondrial KATPChannels

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.