The protective effects of emulsified isoflurane on myocardial ischemia and reperfusion injury in rats.
OBJECTIVE
Pretreatment with volatile anesthetics has been demonstrated to exert cardioprotective effects. The purpose of this study was to examine the effect of emulsified isoflurane, a new formulation of isoflurane in lipid emulsion, administered intravenously in an ischemia and reperfusion model of myocardial injury.


METHODS
Thirty-two Sprague Dawley rats of both sexes were subjected to 30 min of myocardial ischemia followed by 180 min of reperfusion. Each was assigned to one of four pretreatment groups to receive an isovolumetric intravenous infusion of saline: control group, 30% intralipid group, 8% emulsified isoflurane 2 ml kg(-1) group, and sham group (each group, n = 8). The vehicles were administered at a constant rate for 30 min and then discontinued 30 min before left anterior descending coronary artery occlusion. The cardioprotective effects were examined by determining hemodynamics, infarct size, enzyme activity, and cardiomyocytic apoptosis.


RESULTS
Pretreatment with emulsified isoflurane 2 ml kg(-1) (P = 0.000) significantly reduced infarct size (22.6 +/- 2.2%) compared with control (34.8 +/- 2.3%) and 30% intralipid (31.1 +/- 2.9%). When compared with the control and intralipid groups, emulsified isoflurane increased Bcl-2 expression while decreasing Bax and Caspase-3 expression and enhancing Bcl-2/Bax ratios. The apoptotic index in the emulsified isoflurane treatment group showed a significant reduction compared with that in the control group (P = 0.000) and the intralipid group (P = 0.001). In addition, the serum levels of lactate dehydrogenase and creatine kinase were markedly reduced in the emulsified isoflurane treatment group compared with the control and intralipid groups (lactate dehydrogenase, P = 0.015 vs. control; creatine kinase, P = 0.000 vs. control and intralipid).


CONCLUSIONS
These data support a cardioprotective effect of intravenous emulsified isoflurane against myocardial ischemia and reperfusion injury, which are mediated, at least in part, by the inhibition of apoptosis and cell damage.
Hu
Zhao-Yang
ZY
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Luo
Nan-Fu
NF
Liu
Jin
J
D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007530:Isoflurane; D053148:Caspase 3