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(Circulation. 2006;114:I-239 – I-244.)
© 2006 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

How Does Glucose Insulin Potassium Improve Hemodynamic Performance?

Evidence for Altered Expression of Beta-Adrenoreceptor and Calcium Handling Genes

Aaron M. Ranasinghe, MB, MRCS; Christopher J. McCabe, PhD; David W. Quinn, BSc, FRCS; Sally R. James, MBiochem; Domenico Pagano, MD, FRCS, FESC; Jayne A. Franklyn, MD, PhD, FRCP; Robert S. Bonser, MD, FRCP, FRCS

From the Department of Cardiothoracic Surgery (A.M.R., D.W.Q., D.P., R.S.B.), University Hospital Birmingham, Birmingham, UK; Division of Medical Sciences (A.M.R., C.J.M., S.R.J., J.A.F.), University of Birmingham, Birmingham, UK.

Correspondence to Robert Bonser, Department of Cardiothoracic Surgery, University Hospital Birmingham NHS Trust, Birmingham, UK, B15 2TH. E-mail robert.bonser{at}uhb.nhs.uk

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 ß1-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°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.

Key Words: beta-adrenergic receptors • calcium • glucose • hemodynamics • sarcoplasmic reticulum