Glucose-Insulin-Potassium Therapy for Treatment of Acute Myocardial Infarction

Fath‐Ordoubadi, Farzin; Beatt, Kevin J.

doi:10.1161/01.cir.96.4.1152

Cited by 425 publications

(238 citation statements)

References 40 publications

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“…Insulin, as part of the glucose-insulin-potassium (GIK) combination, has long been used as a therapy for acute myocardial infarction and has been shown to significantly decrease in-hospital mortality (8) and overall mortality (24). In isolated cardiac myocytes subjected to ischemia and reoxygenation, administration of insulin reduces apoptosis and protects cells against irreversible injury (12).…”

mentioning

confidence: 99%

Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury

Chai¹,

Wu²,

Li³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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. Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury. Am J Physiol Endocrinol Metab 294: E183-E189, 2008. First published November 14, 2007 doi:10.1152/ajpendo.00571.2007.-Myocardial ischemiareperfusion injury contributes significantly to morbidity and mortality in patients with diabetes. Insulin decreases myocardial infarct size in animals and the rate of apoptosis in cultured cells. Ischemia-reperfusion activates p38 mitogen-activated protein kinase (MAPK), which regulates cellular apoptosis. To examine whether p38 MAPK affects insulin's cardioprotection against ischemia-reperfusion injury, we studied overnight-fasted adult male rats by use of an in vivo rat model of myocardial ischemia-reperfusion. A euglycemic clamp (3 mU ⅐ min Ϫ1 ⅐ kg Ϫ1 ) was begun either 10 min before ischemia (Insulin BI), 5 min before reperfusion (InsulinBR), or 30 min after the onset of reperfusion (Insulin AR ), and continued until the end of the study. Compared with saline control, insulin decreased the infarct size in both Insulin BI (P Ͻ 0.001) and InsulinBR (P Ͻ 0.02) rats but not in Insulin AR rats. The ischemic area showed markedly increased phosphorylation of p38 MAPK compared with the nonischemic area in saline animals. Acute activation of p38 MAPK with anisomycin (2 mg/kg iv 10 min before ischemia) had no effect on infarct size in saline rats. However, it completely abolished insulin's protective effect in Insulin BI and InsulinBR rats. Activation of p38 MAPK by anisomycin was associated with marked and persistent elevation in IRS-1 serine phosphorylation. Treatment of animals with SB-239063, a potent and specific inhibitor of p38 MAPK, 10 min before reperfusion enabled insulin-mediated myocardial protection in Insulin AR rats. We conclude that insulin protects myocardium against ischemiareperfusion injury when given prior to ischemia or reperfusion, and activation of p38 MAPK abolishes insulin's cardioprotective effect.

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mentioning

confidence: 99%

Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury

Chai¹,

Wu²,

Li³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…In consequence, there is an increase of glucose uptake into cardiac muscle. It remains unclear whether the effect of GIK relies on a decrease of FFA and/or an increase in glucose utilization [36]. As insulin decreases blood glucose and potassium levels, potassium and glucose are integral constituents of the GIK regimen to maintain normoglycaemia and normokalaemia.…”

Section: Discussionmentioning

confidence: 99%

“…GIK has been studied in acute myocardial infarction [11,36,37] and cardiac surgery [38][39][40], albeit with variable results and thus no overall benefit [41]. Possible reasons include use of different doses of insulin, failure to maintain normoglycaemia, and introduction after thrombolysis where high blood sugar levels may have enhanced the degree of reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients

Slob

Shulman

Singer

2017

Journal of Critical Care

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Purpose To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage.Materials and methods A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0 Units insulin/kg/hour) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. ResultsOf 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72 hours, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia (<2 mmol/l), hyperglycaemia (>20 mmol/l), hypokalaemia (<2.5 mmol/l) and hyperkalaemia (>7 mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted.Conclusions High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation.

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“…72, 73 Despite that long history, results from trials employing GIK in MI and cardiac surgery are often inconclusive due to small sample sizes and differences of study design and GIK infusions. 74 The dose shown to suppress free fatty acid uptake in the myocardium is 30 g of glucose, 50 units of insulin, and 80 mmol of potassium chloride per liter at 1.5 mL/kg/h. 68 A meta-analysis of randomized clinical trials involving GIK infusions in MI indicated a significant reduction in inpatient mortality for patients receiving GIK compared with conventional treatment.…”

Section: Cardiovascularmentioning

confidence: 99%

“…4 Major criticisms in the majority of trials include defective study design and concomitant therapies with predated thrombolytic and β-blocker therapies. 74 Contemporary studies continue to show conflicting results with GIK infusions. In 1998, a study including 407 MI patients randomized to GIK or control showed a 66% reduction of in-hospital mortality when GIK was added to reperfusion therapy.…”

Section: Cardiovascularmentioning

confidence: 99%

Intensive Insulin Therapy in Critically Ill Patients

2002

N Engl J Med

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Glucose-Insulin-Potassium Therapy for Treatment of Acute Myocardial Infarction

Cited by 425 publications

References 40 publications

Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury

Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients

Intensive Insulin Therapy in Critically Ill Patients

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