| BackgroundHyperglycemia and insulin resistance are common in severe illness patients with or without diabetes. They also generally appear in the patients undergoing heart surgery. Increasing hyperglycemia was found to be independently predictive of increasing mortality , and it had been paid more and more attention by the clinicians in recent years. But there is no unified normative standard for the intensive insulin treatment suiting for children undergoing cardiac surgery with cardiopulmonary bypass.Aims1. To observe the effects of tight glycemic control on organ function and prognosis of patients undergoing valve replacement under cardiopulmonary bypass.2. To investigate the effects and mechanisms of intensive insulin therapy on inflammatory mediators in children undergoing cardiac surgery with cardiopulmonary bypass.3. To investigate the effects and mechanisms of intensive insulin therapy on myocardial function in patients undergoing cardiac surgery with cardiopulmonary bypass.Results1. After operation, the numbers of patients with the peak ALT higher than 80 IU/L, peak AST higher than 80 IU/L, peak creatinine higher than 221μmol/L and peak urea nitrogen higher than 19.3 mmol/L were decreased, and there were significant differences between the two groups (all P<0.05). Compared with RT group, tight glycemic control markedly shorten the length of stay in ICU and length of postoperative hospital stay (both P<0.05).2. In both groups, plasma insulin concentration was increased since the initiation of CPB ,reached the peak 0 h after the termination of CPB ,then it began to decrease. Compared with RT, the levels at different time points after the termination of CPB were higher (P<0.05 or 0.01). In both groups, TNF-α, IL-1βand IL-6 levels was increased since the initiation of CPB ,reached the peak 3 h after the termination of CPB ,then it began to decrease. Compared with RT, the levels at different time points after the termination of CPB were lower in IT (P<0.05 or 0.01). In both groups, IL-10 levels was increased since the termination of CPB ,reached the peak 12 h after the termination of CPB ,then it began to decrease. There was nonsignificantly change between two groups in IL-10 levels(P>0.05). InsR expression in cardiomyocytes in both groups was increased post-CPB(compared with pre-CPB,P<0.05)and after intensive insulin therapy it was significantly higher post-CPB(compared with RT group,P<0.05). In both groups ,NF-κBp65 expression in cardiomyocytes was increased post-CPB(compared with pre-CPB,P<0.05),but no significantly change between two groups post-CPB(P>0.05).3. Compared with RT, dp/dt max, LVEF, FS were higher in IT (P<0.05). After intensive insulin therapy ,InsR expression in cardiomyocytes was significantly higher post-CPB(compared with RTgroup,P<0.05). In cardiomyocytes ,pAkt expression was significantly higher post-CPB(compared with pre-CPB,P<0.05or P<0.01). Compared with RT, post-CPB pAkt expression levels were higher in IT (P<0.05 or P<0.01). GLUT-4 expression in cardiomyocytes was increased post-CPB in IT(compared with RTgroup,P<0.05).Conclusion1. Tight glycemic control may significantly improve the damaged liver and renal function, and shorten the time on ventilator and length of postoperative hospital stay, leading to an improved prognosis in patients undergoing valve replacement under cardiopulmonary bypass.2. Intensive insulin therapy increased InsR expression in cardiomyocytes during paediatric cardiovascular surgery and improved insulin resistance, reduction of TNF-α, IL-1β, IL-6 levels is also its effect. Our study suggested its protective effects to adjust systemic inflammatory reaction symptom.3. Intensive insulin therapy has positive inotropic action on myocardial. Ageing is a reason of insulin resistance. Akt activation inhibition and GLUT-1 transport disorder is the key of insulin resistance post-CPB. Intensive insulin therapy maybe adjust Akt activation, and has up-regulation effect in GLUT-4 transport.
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