BACKGROUND:Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS:Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked β-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.
RCT Entities:
BACKGROUND:Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS:Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked β-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.
Authors: Andra E Duncan; Daniel I Sessler; Hiroaki Sato; Tamaki Sato; Keisuke Nakazawa; George Carvalho; Roupen Hatzakorzian; Takumi Codere-Maruyama; Alaa Abd-Elsayed; Somnath Bose; Tamer Said; Maria Mendoza-Cuartas; Hyndhavi Chowdary; Edward J Mascha; Dongsheng Yang; A Marc Gillinov; Thomas Schricker Journal: Anesthesiology Date: 2018-06 Impact factor: 7.892
Authors: Andra E Duncan; Babak Kateby Kashy; Sheryar Sarwar; Akhil Singh; Olga Stenina-Adognravi; Steffen Christoffersen; Andrej Alfirevic; Shiva Sale; Dongsheng Yang; James D Thomas; Marc Gillinov; Daniel I Sessler Journal: Anesthesiology Date: 2015-08 Impact factor: 7.892
Authors: Houman Ashrafian; Gabor Czibik; Mohamed Bellahcene; Dunja Aksentijević; Anthony C Smith; Sarah J Mitchell; Michael S Dodd; Jennifer Kirwan; Jonathan J Byrne; Christian Ludwig; Henrik Isackson; Arash Yavari; Nicolaj B Støttrup; Hussain Contractor; Thomas J Cahill; Natasha Sahgal; Daniel R Ball; Rune I D Birkler; Iain Hargreaves; Daniel A Tennant; John Land; Craig A Lygate; Mogens Johannsen; Rajesh K Kharbanda; Stefan Neubauer; Charles Redwood; Rafael de Cabo; Ismayil Ahmet; Mark Talan; Ulrich L Günther; Alan J Robinson; Mark R Viant; Patrick J Pollard; Damian J Tyler; Hugh Watkins Journal: Cell Metab Date: 2012-03-07 Impact factor: 27.287