Endocrine Abstracts (2006) 11 P330

How does glucose insulin potassium improve haemodynamic performance? Evidence for beta-adrenoreceptor and sarcoplasmic reticulum calcium ATPase up-regulation

AM Ranasinghe1, DW Quinn2, CJ McCabe1, D Pagano2, JA Franklyn1 & RS Bonser2

1University of Birmingham, Division of Medical Sciences, Birmingham, United Kingdom; 2University Hospital Birmingham NHS Trust, Birmingham, United Kingdom.

Objectives: Glucose insulin potassium (GIK) improves haemodynamic performance following coronary artery bypass graft surgery (CABG). We postulated that this might be secondary to beta-1 adrenergic receptor (ADRB1) up-regulation and changes in myocyte calcium handling.

Methods: We performed a randomised double-blind placebo-controlled trial on patients undergoing first time elective/urgent on-pump CABG (LREC approval obtained). A cohort of 48 patients randomised to receive either pre-ischaemic placebo (5% dextrose) (n=24) or GIK (40% dextrose, K+100 mmol.L−1, Insulin 70 u.l−1) (0.75 ml.kg−1.h−1) underwent left ventricular biopsy immediately prior to aortic cross clamp (AXC), before release of AXC and 10 minutes post-reperfusion. GIK therapy was infused for a mean of 79±21 minutes pre ischaemia. GIK/placebo therapy was terminated 6 hours after removal of AXC. Serial haemodynamic measurements were performed at baseline until 12 hours post removal of AXC. Biopsies were snap frozen and stored at −80 °C, mRNA was extracted and reverse transcribed. Taqman real time PCR was performed to investigate expression of ADRB1and sarcoplasmic reticulum Ca-ATPase (SERCA2a).

Results: Repeated measures analysis demonstrated a statistically significant increase in cardiac index (CI) for the GIK group in the first 6 hours (P=0.037). Taqman RT-PCR showed significantly greater ADRB1 mRNA expression at all time points (4.9-, 7.4- and 15.6-fold increase respectively, P< 0.001) and significantly greater SERCA2a mRNA expression after reperfusion (13.2-fold, P< 0.001) in the GIK group.

Conclusions: The increased haemodynamic performance seen with GIK therapy is associated with increased ADRB1 and SERCA2a mRNA expression. We postulate that ADRB1 and myocyte calcium handling modulation contribute to the beneficial effects of GIK.

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