Isoflurane preconditioning before moderate hypothermic ischemia protects myocardium against ischemia-reperfusion injury via K_(ATP) channels

Objective To test the hypothesis that isoflurane-preconditioning (ISO-P) provides added protection of myocardium with hypothermia against ischemia-reperfusion injury through KATP channels. Methods Thirty-two SD rats of both sexes weighing 230-270 g were studied. The animals were anesthetized with intraperitoneal ketamine 100 mg·kg-1 and heparinized. Chest was opened and heart was immediately removed and perfused in a Langendorff apparatus with oxygenated (95% O2, 5% CO2) Krebs-Hensleit buffer (KHB) for 50 min,followed by 150 min of hypothermic-ischemia (perfusion was suspended and heart was immersed in 17℃ KHB) and 60 min of normothermic reperfusion (heart was again reperfused with 37.7℃ KHB and immersed in 37.7℃ KHB) (I/R). The animals were randomly divided into 4 groups of 8 animals:(l) control group; (2) ISO-P group; (3) ISO-P + GLB group and (4) ISO-P + 5-HD group. The control group received no pretreatment before I/R. In ISO-P group the heart was perfused with KHB gassed with 1% isoflurane for 15 min followed by 15 min wash-out before I/R. In group 3 and 4 the heart was perfused with KHB containing glibenclamide 20μmol·L-1 (group 3) or 5-hydroxydecanoate 150μmol ·L-1 (group 4) in addition to 1% isoflurane before I/R. Cardiac function was measured with a fluid filled latex balloon inserted in left ventricle (LVSP, LVDP, LVEDP, dp/dtmax, dp/dtmin). During hypothermic ischemia left ventricle pressure (LVP),S-time (the interval between the beginning of ischemia to the time point when LVP increased by 1 mm Hg from the baseline pressure) and C-time (the interval between the beginning of ischemia to the time point when LVP was lmmHg below the plateau pressure) were measured. Other criteria included coronary flow (CF),infarct size and creatine kinase.Results (l) S-time and C-time were negatively correlated with infarct size.(2)In ISO-P group (group 2) S-time and C-time were significantly longer during ischemia; LVDP and LVDP x HR were significantly higher during normothermic reperfusion and infarct size was significantly smaller than those in control group (groupl) (P0.05).(3) In ISO-P+ GLB group (group 3) and ISO-P + 5-HD group (group 4) the S-time and C-time were significantly shorter; LVDP and LVDP x HR were significantly lower and the infarct size was significantly larger than those in group 2 (P0.05).Conclusion Isoflurane-preconditioning before moderate hypothennic ischemia provides added cardioprotection against I/R injury which may result from both sKATP and mKATP channel opening. The S-time and C-time during hypothemic ischemia may be used as sensitive indices of cardioprotection.