The Effects Of Ciclosporin A On Myocardium Ischemia Reperfusion Injury

ObjectiveTo investigate the effect of ciclosporin A on myocardial ischemia-reperfusion and explore the possible mechanism of action. Lactate dehydrogenase(LDH) activity, myocardial infarct size, the amounts of high-energy phosphates and cell Na+-K+-ATPase activities, SR Ca2+-ATPase (SERCA) activities, Ca2+uptake and Ca2+release from ryanodine receptors (RyR) were observed.MethodsSeventy-two Wistar rats were randomly divided into three groups:controls (CON, n=24), ischemia-reperfusion (IR, n=24) and ciclosporin A (CsA, n=24). Isolated rat hearts were mounted on a Langendorff perfusion apparatus.In CON group, isolated rat hearts were perfused with Krebs-Henseleit (K-H) solution for90min. In IR group, isolated rat hearts were perfused with K-H solution for30min, ischemia for30min and then reperfused for30min; In the CsA group, isolated rat hearts were perfused succesively with K-H solution for10min and K-H solution containing CsA0.1mmol/L for20min,then the hearts were subjected to30min global myocardial ischemia and then30min reperfusion. In each group, eight hearts were randomly selected to measure the LDH activity and the myocardial infarct size, eight were selected to assay intracellular high-energy phosphates by high-performance liquid chromatography (HPLC),the others eight were used to separate sarcoplasmic reticulum(SR) vesicles by ultracentrifugation, measuring their Ca2+-ATPase (SERCA) and Na+-K+-ATPase activities、Ca2+uptake and Ca2+release from ryanodine receptors (RyR).Result1Compared to IR group,the LDH activity and the myocardial infarct size in CsA group were reduced by31.33%and26.16%respectively (P<0.05).2The levels of high-energy phosphates in CsA-treated group were significantly increased as compared with the ischemia-reperfusion group without CsA treatment (P<0.05).3In CsA group, RyR exhibited a decreased initial velocity and maximum of Ca2+release in comparison to IR group, while the two index in CON group is lower than those in IR and CsA group(P<0.05).4SR vesicles SERCA and Na+-K+-ATPase activities had significant differences between IR and CsA group, while the two index in CON group is higher than those in IR and CsA group(P<0.05).Conclusions1Ciclosporin A pretreatment can reduce the myocardial infarct size and the LDH release from myocardial cells and protects the ischemia-reperfused myocardium. The activity of CaN decreased in CsA group compared to IR group, indicates CsA inhibited the activity of CaN. In CsA group, the infarcted size reduced31.33%compared to IR group, indicates CsA can alleviate the apoptosis of myocardium through inhibiting the activity of CaN.2Na+-K+-ATPase activities in CsA group had significant lower than IR group, thus enhance the content of ATP in myocardium.Ciclosporin A pretreatment can raise the level of high-energy phosphates and attenuate the ischemia-reperfusion injury.3In CsA group, RyR exhibited a decrease initial velocity and maximum of Ca2+release and a increase activity of Ca2+-ATPase in comparison to IR group.Ciclosporin A pretreatment protects the heart against ischemia-reperfusion injury through inhibiting calcium overload from RyR probably.