title: Emulsified isoflurane protects rat heart in situ after regional ischemia and reperfusion.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Hu
authors.forename: Xia-Ying
authors.initials: XY
authors.lastname: Peng
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004655:Emulsions; D004734:Energy Metabolism / Q000187:drug effects; D057775:Ischemic Postconditioning / Q000379:methods; D007530:Isoflurane / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D004655:Emulsions; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D045304:Cytochromes c; D007530:Isoflurane
keywords: emulsified isoflurane; ischemia/reperfusion injury; mitochondria