改良极化液对体外循环小型猪动物模型心肌保护作用

目的探讨改良极化液对体外循环（ECC）小型猪心脏功能保护作用研究。方法小型猪12头随机分为两组，组1为对照（CON）组，麻醉后经外周静脉输入乳酸林格氏液20m／h；组2为极化液（GIK）组，与CON组在同一时间以同样速度输注GIK。全麻诱导插管后，建立ECC，过程为转机、阻闭、开放各30min后停止ECC。检测麻醉诱导后至开放升主动脉120min期间的血糖（BG）、乳酸（Lac）、平均动脉压（MAP）、左心室舒张末压（LVEDP）和左心室收缩峰压（LVPSP），并计算左心室发展压（LVDP）变化，同期对心肌组织行电镜检测及Western blotting分析。结果ECC后两组BG水平显著上升，在开放升主动脉120min时达峰值，胰岛素水平也显著升高，但两组间无显著性差异（P〉0．05）；两组Lac水平在ECC后有所上升，在开放升主动脉后上升更为显著，GIK组显著低于CON组，在ECC5min、开放升主动脉60min及120min有显著性差异（P〈0．05）；所有实验猪在ECC后MAP及心室压力出现显著变化，表现为除LVEDP外的所有压力值均有不同程度下降，而LVEDP显著升高，GIK组LVPSP、LVDP在开放升主动脉80min后显著高于CON组（P〈0．05）；GIK组MAP在开放升主动脉20min后即表现为高于CON组（P〈0．05）；而GIK组的LVEDP在开放升主动脉后一直低于CON组（P〈0．05）。电镜结果显示：ECC后CON组心肌线粒体明显肿胀，而GIK组线粒体改变远较CON组为轻，Western blotting检测结果提示GIK组蛋白激酶B（Akt）磷酸化程度显著高于CON组，而6-磷酸果糖氨基转位酶（GAFT）又显著低于CON组。结论ECC下心脏手术可导致不同程度心肌损伤，进而引起应激性高血糖、乳酸增高、心肌收缩功能降低，而GIK对ECC后心肌细胞有明显保护作用，其机制与GIK有效激活Akt通道，降低己糖胺活性有关。

Protective Effects of glucose-insulin-potassium on cardiac function in extracorporeal circulation Mini Pig Model

Objective To explore the myocardial protective effect of glucose-insulin-potassium(GIK) on minipigs during extracorporeal circulation(ECC) procedure.Methods 12 miniature pigs were randomly divided into two groups.In the control group(CON),lactated Ringer’s solution 20 ml/h was administrated after anesthesia for the whole ECC procedure.In the modified GIK group,GIK for the whole ECC porcedure was administrated.ECC was processed for total 90 minutes: 30 minutes before aortic clamping,30 minutes under aorta clamping and 30 minutes after aortic declamping.The blood glucose(BG) and lactate(Lac) concentration,mean arterial pressure(MAP) and ventricular pressure change on scheduled timing were measured.Also the myocardial tissue was collected for electron microscopy and immunoblotting assay.Results The BG level of both groups was significantly increased after ECC.At 120 min of aortic decamping BG reached the peak value.Insulin levels also increased but showed no significant differences.The Lac level in boths group has increased after ECC,but it was significantly lower in the GIK group than that in the CON group at the time of 5 min after ECC,60 min and 120 min after aortic declamping.The MAP and ventricular pressure were significantaly changed in all minipigs during ECC.After ECC,left ventricular end-diastolic pressure(LVEDP) significantly increased,while other pressure values significantly decreased in both groups.The left ventricular peak systolic pressure(LVPSP) and left ventricular diastolic pressure(LVDP) of GIK group were significantly higher compared to the CON group at the time of 80 min after aortic declamping(P<0.05).The MAP value of GIK group was significantly higher than the CON group in all scheduled time after 20 min after aortic declamping(P<0.05).But the LVEDP was lower in GIK group than in CON group(P<0.05).The electron microscopy results showed that: mitochondria edema could be observed in CON group and GIK group after ECC,but it was mitigated in the GIK group.The Western blot analysis results suggested that in GIK group the phosphorylation of Akt was significantly higher than the CON group,while the GFAT level was significantly lower than CON group. Conclusion ECC itself can cause of myocardial injury,thereby cause stress induced hyperglycemia,increased lactate and reduced myocardial contractile function.GIK has protective effects on myocardial cells after ECC.The mechanisms is that GIK can effectively active the Akt pathway and reduce the activity of the hexosamine pathway.