The Role PI3K Plays During Myocardial Insulin Resistance Induced By Canine CPB Ischemia Reperfusion

Objective:The test is aimed at testing the PI3K in the process of myocardial insulin resistance brought about by extracorporal circulation ischemia reperfusion, making clear whether myocardial cells induce the transfer of Glut-4 by way of PI3K, and further probing into the mechanism of insulin resistance post-receptor in the course of CPB ischemia. Methods:24 mongrel dogs fall randomly into 4 groups. Group I undergoes 30-minute aortic occlusion; groupⅡ120-minute aortic occlusion; groupIII 30-minute aortic occlusion plus insulin—PI3K activator; groupⅣ30-minute aortic occlusion plus wortmannin—PI3K inhibitor. Samples of arterial blood, coronary venous sinus blood and cardiac tissue are simultaneously collected before CPB bypass and 15 minutes,45 minutes and 75 minutes later after cross-clamp removal. Radioimmunoassay is exercised in testing and comparing glucose and insulin in each blood sample groups, and in comparing the change of plasma glucose, insulin and insulin resistance index at the corresponding points of time. PCR is practiced in detecting the activity of PI3K; while immunohistochemistry is employed in detecting the change of myocardial cell envelope and cytoplastic Glut-4, using the left ventricular myocardium taken at the corresponding point of time as a sample. Results:1. Myocardial Glucose Metabolism:Plasma glucose, after ischemia reperfusion, grows notably denser to various degrees than prior to bypass, peaking at the 15th minute after ischemia reperfusion (p<0.05). GroupⅡ, compared with groupⅠ, increases more significantly in the amount of plasma glucose following the ischemia reperfusion (p<0.05). Plasma glucose density groupIVturns even much higher than the first two groups and last much longer (p<0.01).2. Insulin Resistance Index:IRI in the four tested groups appear noticeably higher in the course of extracorporal circulation, peaking at the 15th minute after ischemia reperfusion. And at the 75 minute it still remains at a high level, further, the differences are conspicuous, as opposed to the amount previous to bypass (p<0.05). IRI in GroupⅡand groupⅣ, as against groupⅠ, stays much higher, takes more time to recover and last longer (p<0.05).3. Cardiac Function:At the 15th minute after the myocardial ischemia reperfusion each group lower strikingly in the left ventricular systolic pressure as well as in the maximum rate of left ventricular pressure rise, and goes up remarkably in the left ventricular end-diastolic pressure and resume to their original levels gradually. GroupⅡ, as against groupⅠ, is conspicuous in changes and slow in recovery after ischemia reperfusion. GroupⅣ,however, compared with groupⅡ, falls notably in LVSP and +dp/dtmax and rises notably in LVEDP (p<0.01).4. Glut-4 Membrane Percentage of Myocardial Cells:As against the percentage prior to bypass, the membrane percentage of groupⅠ-Ⅳreaches the nadir at the 15th minute and goes up slowly to various degrees at the 75th minute after the ischemia reperfusion. The membrane of percentage of Glut4 of groupⅣ, in contrast, continues to decrease till reaching the nadir at the 75th minute (p<0.01). groupⅡ, in comparison with groupⅠ, goes down strikingly in the membrane percentage and lasts a longer time(p<0.05). while groupⅣ, in contrast with groupⅢ, drops more significantly in its membrane percentage and sustains much longer (p<0.01).5. Change of PI3K:The cardiac myocyte PI3K declines to various extents after the ischemia reperfusion. GroupⅣdrops notably in its myocardial cell compared to groupⅠ(p<0.01), whereas groupⅢstrengthens in its PI3K (p<0.05).Conclusion:After the CPB ischemia reperfusion, PI3K, as a key signal transduction factor, stimulates the transfer of myocardial cell Glut-4 from the cytoplasma to the envelope, thus assimilating glucose, namely, myocardial cell Glut-4 is mainly transferred by way of PI3K in the process of myocardial insulin resistance induced by ischemia reperfusion.