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

• Published in: Circulation (New York, N.Y.) Vol. 114; no. 1; pp. I239 - 239-I-244
• Main Authors: RANASINGHE, Aaron M, MCCABE, Christopher J, QUINN, David W, JAMES, Sally R, PAGANO, Domenico, FRANKLYN, Jayne A, BONSER, Robert S
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 04.07.2006
• Subjects: Aged; Aorta; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation; Blood. Blood coagulation. Reticuloendothelial system; Calcium-Binding Proteins - biosynthesis; Calcium-Binding Proteins - genetics; Calcium-Transporting ATPases - biosynthesis; Calcium-Transporting ATPases - genetics; Cardiology. Vascular system; Cardioplegic Solutions - pharmacology; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cohort Studies; Constriction; Coronary Artery Bypass; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Gene Expression Regulation - drug effects; Glucose - pharmacology; Heart Arrest, Induced - methods; Heart Ventricles - metabolism; Heart Ventricles - pathology; Hemodynamics - drug effects; Humans; Insulin - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Myocardial Reperfusion; Pharmacology. Drug treatments; Potassium - pharmacology; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-1 - biosynthesis; Receptors, Adrenergic, beta-1 - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Up-Regulation - drug effects; Pancreatic hormone; Calcium; Sarcoplasmic reticulum; beta-adrenergic receptors; Cardiovascular disease; Glucose; Hemodynamics; Adrenergic receptor; Inorganic element; Insulin; Potassium
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.105.000760

Glucose insulin potassium (GIK) improves hemodynamic performance after coronary artery surgery (CABG). We investigated whether this is associated with changes in gene expression of beta1-adrenergic receptor (ADRB1) or other calcium handling proteins. 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. 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.