Effect of glucose–insulin–potassium on hyperlactataemia in patients undergoing valvular heart surgery

Roh, Go Un; Shim, Jæ Kwang; Song, Jong Wook; Kang, Hye Min; Kwak, Young Lan

doi:10.1097/eja.0000000000000250

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…More than 50 years ago the clinical application of glucose insulin-potassium (GIK) solution was presented in cardiac surgery. 17,18,24,25 The study has found insulin is a key component of GIK protecting the myocardium after cardiac surgery. Previous studies have shown the protective effects of insulin on cardiovascular by anti-apoptotic, anti-inflammatory, anti-oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin regulates glucose levels and has anti-apoptosic and anti-inflammatory effects [14][15][16] ; it has been widely used in clinical treatment of diabetes, metabolic syndrome, and MIRI. [17][18][19] Insulin was reported to inhibit the NLPR3 inflammasome activation 14 and enhance PDHc activity by PDHA1 dephosphorylation. 15 Nevertheless, the contributions and molecular mechanisms of PDHA1 in association with insulin and NLRP3-induced pyroptosis in MIRI are still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury

et al. 2022

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Background Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. Methods Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. Results It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. Conclusions Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury

et al. 2022

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“…3,46 Variable degrees of hyperglycemia may explain why GIK demonstrated benefit in some investigations 12,28 but not in others. 29,47,48…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications

et al. 2018

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Background Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery. Methods This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl–1; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl–1. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients. Results At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl–1 with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl–1) occurred in 6 (0.9%) patients. Conclusions Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

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Cardioprotective Effects of Glucose-Insulin-Potassium Infusion in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis

Hagerman

Schorer

Alessandro

et al. 2024

Seminars in Thoracic and Cardiovascular Surgery

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Effect of glucose–insulin–potassium on hyperlactataemia in patients undergoing valvular heart surgery

Abstract: Clinicaltrials.gov identifier: NCT01825720.

Cited by 3 publications

References 41 publications

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury

Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications

Cardioprotective Effects of Glucose-Insulin-Potassium Infusion in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis

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