ABSTRACT
OBJECTIVE： To investigate the effects of adiponectin （APN） on the expression of myocardial AMPK in myocardial insulin resistance （IR） model dogs during cardiopulmonary bypass （CPB）. METHODS： Totally 24 dogs were randomly divided into control group， model group， APN group （36 μg/kg）， AMPK inhibition group （APN 36 μg/kg+AMPK inhibitor compound C 0.5 mg/kg）， with 6 dogs in each group. All dogs underwent CPB； except for control group without medicine， CPB myocardial IR model were established in other groups， and perfused with St.Thomas cardiac cardioplegia lipid no medicine or containing relevant drugs after main artery block. Coronary sinus blood and carotid artery blood samples were collected before bypass and after 15， 90 min reperfusion following 60 min myocardial ischemia. Left ventricular apical tissue was taken， and the uptake rate of myocardial glucose and insulin resistance index （IRI） were determined and calculated； the changes of myocardial injury indexes （cTnT concentration） and cardiac function indexes （LVSP， +dp/dtmax） were monitored. The level of p-AMPK was detected. RESULTS： There was no statistical significance in above indexes of dogs before bypass （P＞0.05）. Compared with control group， the rate of myocardial glucose uptake， the levels of LVSP， +dp/dtmax and p-AMPK in model group were decreased significantly after 15， 90 min reperfusion （P＜0.05）， and the concentrations of IRI and cTnT were increased significantly （P＜0.05）. Compared with model group， the rate of myocardial glucose uptake， LVSP， +dp/dtmax and p-AMPK were increased significantly in APN group and AMPK inhibitor group （P＜0.05）， while the concentrations of IRI and cTnT were decreased significantly （P＜0.05）； moreover， the effect of APN group was better than that of AMPK inhibitor group （P＜0.05）. CONCLUSIONS： APN can promote myocardial glucose uptake and metabolism， and contribute the recovery of cardiac function， the mechanism of which may be associated with increasing the activity of AMPK.
ABSTRACT
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 rel-evant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid(FFA),creatine kinase isoen-zyme(CK-MB)concent in venous sinus plasma and adenosine triphosphate(ATP)content in mitochondria were detected and calcu-lated before bypass and after 15,60,90 min of reperfusion. Left ventricular systolic pressure(LVSP)and left ventricular end dia-stolic pressure(LVEDP)were analyzed,and mRNA expression of adenylate-activated protein kinase(AMPK)and protein expres-sion 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.
ABSTRACT
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 rel-evant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid(FFA),creatine kinase isoen-zyme(CK-MB)concent in venous sinus plasma and adenosine triphosphate(ATP)content in mitochondria were detected and calcu-lated before bypass and after 15,60,90 min of reperfusion. Left ventricular systolic pressure(LVSP)and left ventricular end dia-stolic pressure(LVEDP)were analyzed,and mRNA expression of adenylate-activated protein kinase(AMPK)and protein expres-sion 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.