Protective effect of isoflurane preconditioning on myocardium against ischemia-reperfusion injury in isolated rat hearts

Objective To investigate the protective effect of isoflurane preconditioning on myocardium against isehemia-reperfusion(I/R)injury and the possible mechanism.Methods Fifty male SD rats weighing 250- 300 g were randomly divided into 5 groups(n=10 each):Ⅰ control group(C);Ⅱ I/R group and 3 isoflurane preconditioning groups with 0.5%(Ⅲ),or 1.0%(Ⅳ)or 2.0% isoflurane(Ⅴ).The animals were anesthetized with intraperitoneal pentobarbital 40 mg·kg~(-1).The hearts were immediately excised and placed in cold K-H solution.The aorta was canuulated and heart retrogradely perfused with K-H solution aerated with 95% O_2 and 5% CO_2 at 37℃ and 10 kPa in a langendorff apparatus.Left ventricular end-diastollc pressure(LVEDP)and left ventrieular systolic pressure(LVSP)were measured from a fluid-filled latex balloon in the left ventricle.The isolated hearts were made globally ischemic for 30 min followed by 60 rain reperfusion in group Ⅱ-Ⅴ.In the 3 isoflurane preconditioning groups the hearts were perfused with K-H solution saturated with 0.5% or 1.0% or 2.0% isoflurane for 15 rain followed by 15 rain washout before ischemia.The cardiac function variables including LVEDP,LVSP dp/dt_(min),dp/dt_(max) and HR were measured after epuilibrium(baseline values),immediately before ischemia,at the end of 30 min ischemia and 60 min reperfusion.The infarct size and cytochrome C level in cytoplasm and mitochondria of myocytes were measured.Results I/R significantly increased LVEDP and decreased LVSP,dp/dt_(min),dp/dt_(max) as compare with control group.Sevoflurane preconditioning significantly attenuated the depression of cardiac function caused by I/R.Only LVEDP was significantly higher during reperfusion period in the 3 sevoflurane preconditioning group than in the control group but there was no significant difference in LVSP,dp/ dt_(min),dp/dt_(max) between control group and the 3 preconditioning groups.The infarct size was significantly smaller in the 3 preconditioning groups than in I/R group.Cytochrome C level was significantly increased in cytoplasm but decreased in mitochondria in I/R group as compared with control group.Sevoflurane preconditioning significantly ameliorated the release of cytochrome C from mitochondria to cytoplasm in the 3 sevoflurane preconditioning group.Conclusion Isoflurane preconditioning can protect the heart against I/R injury by attenuation of the release of cytochrone C from mitochondria to cytoplasm.