Volatile anesthetic postconditioning reduces myocardial infarct size against ischemia/reperfusion (I/R) injury. We tested the hypothesis that emulsified isoflurane (EIso) administrated after ischemia exerts cardioprotection in a rat model of myocardial I/R. Male SD rats underwent 30-min coronary occlusion followed by 3-h reperfusion except for sham rats. All vehicles were administrated intravenously at reperfusion onset for 30 min. In the first study, 56 rats were given saline (CON), 30% intralipid (IL) and 1, 2, 4, 8 or 16 mL/kg EIso for infarct size measurement. In a second study, 32 rats were randomized to four groups and administrated saline in sham (sham) and control (CON) groups, 30% intralipid in IL group and 2 mL/kg emulsified isoflurane in EIso group. Cardiomyocytic enzyme activity was determined. Myocardial mitochondria and cytosol were isolated to determine mitochondrial energy metabolism, cytochrome c release, mitochondrial membrane potential (ΔΨm) and opening of the mitochondrial permeability transition pore (mPTP). Morphologic changes in mitochondria were observed by transmission electron microscopy. Compared with CON and IL, 2, 4 and 8 mL/kg EIso limited infarct size (P < 0.01). Serum levels of cardiac enzyme leakage were reduced in EIso-treated hearts compared with CON (P < 0.01 or P < 0.05). EIso preserved the ultrastructure of mitochondria, protected against mPTP opening, decreased cytochrome c release and preserved ATP production and ΔΨm . In conclusion, EIso is effective in reducing infarct size and in preserving mitochondrial function after ischemia and reperfusion injury.
Keywords: emulsified isoflurane; ischemia/reperfusion injury; mitochondria.
© 2013 The Authors Fundamental and Clinical Pharmacology © 2013 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.