Isoflurane preconditioning protects against ischemia-reperfusion injury partly by attenuating cytochrome c release from subsarcolemmal mitochondria in isolated rat hearts.
OBJECTIVE
To examine if isoflurane preconditioning can attenuate ischemia/reperfusion injury by reducing cytochrome c release from inner mitochondrial membrane.


METHODS
Isolated hearts of Sprague-Dawley rats were perfused on Langendorff apparatus. Hearts were randomly assigned to a non-treated group (CON group, n=12) or three isoflurane preconditioning groups (0.5% ISC group, 1.0% ISC group, and 2.0% ISC group; n=12). In the latter three groups, isoflurane was given at concentrations of 0.5%, 1.0%, and 2.0% for 15 min with 15-min washout before 30-min ischemia. Subsarcolemmal mitochondria of the myocardium were isolated after 60-min reperfusion. Hemodynamics of the each heart was recorded, infarct size of the hearts and contents of cytosolic cytochrome or mitochondrial cytochrome c were measured at the end of reperfusion. Morphology of isolated mitochondria in the four groups was evaluated, respectively.


RESULTS
Compared with the CON group, cytosolic cytochrome c in 0.5% ISC group, 1.0% ISC group, and 2.0% ISC group were significantly decreased along with a significant increase of mitochondrial cytochrome c. Infarct size of the hearts in the four groups were 56%+/-12%, 41%+/-12%, 32%+/-7% and 33%+/-11%, respectively. The values of the three isoflurane preconditioning groups were significantly lower than that of the CON group (P<0.05). Isoflurane exposure before ischemia can attenuate the change of morphology of mitochondria after reperfusion. The effects of 2.0% isoflurane on reducing cytochrome c release were more remarkable than 0.5% and 1.0% concentrations of isoflurane.


CONCLUSIONS
Myocardioprotective effects of isoflurane preconditioning were associated with attenuation of cytochrome c loss from the inner membrane of subsarcolemmal mitochondria.
Qian
Li-Ping
LP
Jiangsu Provincial Key Lab of Anesthesiology, Jiangsu Institute of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China.
Zhu
Shan-Shan
SS
Cao
Jun-Li
JL
Zeng
Yin-Ming
YM
D000818:Animals; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000648:ultrastructure; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017725:Ventricular Pressure / Q000187:drug effects
D045304:Cytochromes c; D007530:Isoflurane