How does glucose insulin potassium improve hemodynamic performance? - Evidence for altered expression of beta-adrenoreceptor and calcium handling genes

Article; Proceedings Paper

关键词: MYOCARDIAL PROTECTION;    BETA(1)-ADRENERGIC RECEPTORS;    RAT-HEART;    PHOSPHOLAMBAN;    ISCHEMIA;    SURGERY;    MUSCLE;    TRIAL;   

DOI  :  10.1161/CIRCULATIONAHA.105.000760

来源: SCIE

【 摘 要 】

Background-Glucose insulin potassium (GIK) improves hemodynamic performance after coronary artery surgery (CABG). We investigated whether this is associated with changes in gene expression of beta 1-adrenergic receptor (ADRB1) or other calcium handling proteins. Methods and Results-During a randomized double-blind placebo-controlled trial, 48 patients undergoing on-pump CABG, allocated to receive pre-ischemic placebo (5% dextrose) or GIK (40% dextrose, K+ 100 mmol.L-1, insulin 70 u.L-1; 0.75 mL.kg(-1).h(-1)) continued for 6 hours after the removal of the aortic cross-clamp (AXC), underwent left ventricular biopsy for analysis of specific mRNAs immediately before AXC, before release of AXC, and 10 minutes after reperfusion (placebo n = 24, GIK n = 24). GIK or placebo was infused for a mean of 79 +/- 21 minutes or 79 +/- 18 minutes pre-ischemia respectively. Serial hemodynamic measurements were performed. Biopsy samples were snap-frozen and stored at -80 degrees C, mRNA was extracted and TaqMan real-time polymerase chain reaction was performed to investigate expression of ADRB1, sarcoplasmic reticulum Ca-ATPase (SERCA2a), and phospholamban (PLB). GIK significantly increased cardiac index versus placebo (P = 0.037). TaqMan reverse-transcriptase polymerase chain reaction showed significantly greater ADRB1 mRNA expression at all time points (4.9-fold, 7.4-fold, and 15.6-fold increase, respectively; P < 0.001), significantly greater SERCA2a mRNA expression after reperfusion (13.2-fold; P < 0.001), and increased PLB mRNA expression at pre-ischemia and reperfusion (P < 0.001 for both time- points) in GIK groups versus placebo. Conclusions-The beneficial hemodynamic effects of GIK therapy are associated with increased ADRB1 and SERCA2a mRNA expression. Further work is therefore warranted to investigate these mRNA effects at the protein level.

【 授权许可】

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