Effects of ischemic preconditioning with atorvastatin on heart ischemia-reperfusion injury and possible mechanism

Abstract

Objective To investigate the effects of pretreatment with atorvastatin (Ator) on the heart ischemia-reperfusion injury (IRI) and the possible mechanism.Methods After establishment of IRI models,66 healthy male SD rats were divided into three experimental groups (n =22 each).In control group,the rats were given cardiac perfusion continuous buffer.In IRI group,myocardia of rats accepted 30 min global ischemia and 120 min reperfusion.In Ator group,the rats were given 1 μmol/L Ator befor ischemia,and perfused for 30 min,followed by IRI.The myocardial ultrastructure,infarct size,hemodynamic,serum lactate dehydrogenase levels,adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD +) levels in three groups were observed.Results In IRI group and Ator group,arched upward ST segment elevation and T wave fusion after the anterior descending artery ligation were seen.The electrocardiogram (ECG) in the control group had no significant change after surgery.As compared with the IRI group,the myocardial infarction area in the Ator group was significantly decreased (P ＜ 0.05).Microstructure showed that there was significant difference in the cardiomyocytes edema,myofibril,mitochondrial structure and glycogen granules among the three groups.After ischemia-reperfusion,the left ventricular systolic pressure (LVSP),peak velocity of left ventricular pressure drop (dp/dtmin) and heart rate (HR) values in the IRI group were decreased significantly,and the left ventricle end-diastolic pressure (LVEDP) values increased significantly (P ＜ 0.05) as compared wiht the Ator group (P ＜ 0.05).The lactate dehydrogenase (LDH) levels in the control group,IRI group and Ator group were (164.32 ± 20.84),(3589.63 ± 133.25) and (1703.25 ± 155.80) U/L respectively.The LDH levels in the IRI group were lower than in the control group,and those in IRI group were higher than in the Ator group (P ＜ 0.05).The myocardial ATP and NAD + levels in the IRI group were decreased significantly as compared with the control group (P ＜ 0.05),and increased as compared with the Ator group (P ＜ 0.05).Conclusion Ischemic preconditioning with Ator for IRI can play an effective role in myocardial protection,which is achieved by activating the mitochondrial ATP-sensitive potassium channels and reducing lactic acid-mediated expression. Key words: Ischemic preconditioning; Ischemia reperfusion injury; Atorvastatin; Myocardial protection