OBJECTIVE: To explore the effects of acadesine on myocardial energy metabolism of model dogs with myocardial ischemia-reperfusion injury (MIRI) after cardiopulmonary bypass (CPB). METHODS: Dogs were randomly divided into control group, model group, acadesine low-dose, high-dose groups (0.8, 3.2 mg/kg), 6 in each group. All dogs received CPB. Except for control group, dogs in other groups were reduced for MIRI model, and perfused St.Thomas cardiac cardioplegia lipid containing relevant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid (FFA), creatine kinase isoenzyme (CK-MB) concent in venous sinus plasma and adenosine triphosphate (ATP) content in mitochondria were detected and calculated before bypass and after 15, 60, 90 min of reperfusion. Left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were analyzed, and mRNA expression of adenylate-activated protein kinase (AMPK) and protein expression of phosphorylated AMPK (p-AMPK) in myocardial tissue were detected. RESULTS: Before bypass, all indexes in each group had no statistic significances (P>0.05). After bypass, compared with control group, uptake rates of myocardial glucose and FAA, ATP content, mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in model group and each administration group were obviously decreased (P<0.05); LVEDP and CK-MB concent in plasma were obviously increased (P<0.05). Compared with model group, uptake rates of myocardial glucose and FAA, ATP content, mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in each administration group were obviously increased (P<0.05); LVEDP and CK-MB concent in plasma were obviously decreased (P<0.05); and high-dose group showed more obvious change than that of low-dose group (P<0.05). CONCLUSIONS: Acadesine can promote the AMPK phosphorylation, contribute to the myocardial glucose and FFA uptake to promote the increase of ATP in myocardial mitochondria and relieve MIRI after CPB.
关键词
阿卡地新体外循环犬心肌缺血再灌注损伤心肌能量代谢
Keywords
AcadesineCardiopulmonary bypassDogsMyocardial ischemia-reperfusion injuryMyocardial energy metabolism