Reversal of myocardial dysfunction in endotoxin shock with insulin

Archer, L. T.; Beller, B. K.; Drake, J. K.; Whitsett, Thomas L.; Hinshaw, Lerner B.

doi:10.1139/y78-017

Cited by 16 publications

(7 citation statements)

References 3 publications

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“…Insulin was also found to augment myocardial contractility in the normal newborn piglet heart (15), rat heart under conditions of normal perfusion (4,19), and increased pressure and volume workload (15). Archer et al (1) in a canine endotoxin shock model were able to reverse, by the infusion of massive doses of insulin, all signs of myocardial dysfunction, advocating the clinical use of glucose-insulin-potassium.…”

Section: Discussionmentioning

confidence: 99%

The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart

1985

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Controversy exists in the literature concerning the effects of insulin and glucagon on cardiac muscle contractility, in particular during anoxia, ischemia or sepsis. The purpose of the present study was to determine the effects of insulin and glucagon on the systolic function of the normal and the dysfunctioning septic rat myocardium in the Langendorff preparation. In the normal isolated rat heart, neither insulin nor glucagon exhibited any lasting inotropic effect on systolic function or coronary flow. Sepsis (cecal ligation and puncture) resulted in a dramatic reduction of systolic function to 44% of control animals. All insulin-containing formulations tested improved systolic function in septic hearts by a mean of 85% compared to Krebs and glucose only. However, this improvement did not reach statistical significance compared to the use of Krebs and glucose only. Glucagon at 100 micrograms/l was doing as well as Krebs and glucose alone while at 1 mg/l glucagon was only able to maintain pre-perfusion contractility. Our results suggest that neither insulin nor glucagon seem to possess special inotropic properties for the isolated perfused normal or septic rat heart.

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Section: Discussionmentioning

confidence: 99%

The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart

1985

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“…Those findings suggest that maintaining blood glucose concentrations at 110 mg/dl or less is critical in obtaining the benefits of insulin administration. This is supported by the observation that cardiac dysfunction induced by endotoxin administration was not related to arterial blood glucose concentrations [57,58]. Furthermore, infusions of insulin reversed cardiac failure and maintained normal performance in spite of wide ranges in glucose concentrations (5–120 mg/dl), suggesting that myocardial dysfunction is not precipitated or induced by the hypoglycemia of endotoxin shock.…”

Section: Is It Glucose or Insulin That Is Critical To The Heart?mentioning

confidence: 78%

Untitled

Das¹

2002

Crit Care

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Stress hyperglycemia and diabetes mellitus with myocardial infarction are associated with increased risk for in-hospital mortality, congestive heart failure, or cardiogenic shock. Hyperglycemia triggers free radical generation and suppresses endothelial nitric oxide generation, and thus initiates and perpetuates inflammation. Conversely, insulin suppresses production of tumor necrosis factor-α and free radicals, enhances endothelial nitric oxide generation, and improves myocardial function. It is proposed that the balance between insulin and plasma glucose levels is critical to recovery and/or complications that occur following acute myocardial infarction and in the critically ill. Adequate attention should be given to maintaining euglycemia (plasma glucose ≤ 110 mg/dl) in order to reduce infarct size and improve cardiac function while using a glucose–insulin–potassium cocktail.

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“…Our other subgroup analyses were to examine only populations of septic shock and other forms of circulatory shock; however, we were unable to identify any experimental studies examining these groups of patients. This was surprising to us given the amount of basic science research that supports the potential physiological benefits of GIK therapy for septic shock 48 – 52 . Because we specifically sought out studies of septic shock and were unable to include any in the analysis, this study adds to previously published meta‐analyses of GIK by allowing a conclusion that the current literature provides an absence of evidence regarding the effect of GIK as a therapy for septic shock.…”

Section: Discussionmentioning

confidence: 96%

Effect of Glucose—Insulin—Potassium Infusion on Mortality in Critical Care Settings: A Systematic Review and Meta‐Analysis

Puskarich

Runyon

Trzeciak

et al. 2009

The Journal of Clinical Pharma

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This study seeks to measure the treatment effect of glucose-insulin-potassium (GIK) infusion on mortality in critically ill patients. A systematic review of randomized controlled trials is conducted, comparing GIK treatment with standard care or placebo in critically ill adult patients. The primary outcome variable is mortality. Two authors independently extract data and assess study quality. The primary analysis is based on the random effects model to produce pooled odds ratios (ORs) with 95% confidence intervals (CIs). The search yields 1720 potential publications; 23 studies are included in the final analysis, providing a sample of 22 525 patients. The combined results demonstrate no heterogeneity (P = .57, I 2 = 0%) and no effect on mortality (OR = 1.02; 95% CI, 0.93-1.11) with GIK treatment. No experimental studies of shock or sepsis populations are identified. This meta-analysis finds that there is no mortality benefit to GIK infusion in critically ill patients; however, study populations are limited to acute myocardial infarction and cardiovascular surgery patients. No studies are identified using GIK in patients with septic shock or other forms of circulatory shock, providing an absence of evidence regarding the effect of GIK as a therapy in patients with shock. KeywordsClinical research; critical care; emergency medicine; clinical trials; anesthesiology Infusion of a glucose-insulin-potassium (GIK) solution was first proposed in the 1960s as treatment for acute myocardial infarction (AMI) with the intention of providing electrical stability to the myocardium. 1 The proposed mechanisms of action of GIK therapy in cardiovascular disease include suppression of circulating levels and myocardial uptake of free fatty acids, which are toxic to ischemic myocardium; improvement in the efficiency of myocardial energy production through the provision of exogenous glucose; and stabilization of intracellular potassium, which may be depleted during times of myocardial ischemia. 2,3 Since the sentinel report, numerous randomized controlled trials have been performed using GIK. Pooled data have suggested morbidity and mortality benefits associated with GIK therapy in cardiothoracic surgery 4 and AMI 3 populations. The largest GIK study performed in AMI patients to date failed to find similar benefits. 2 Thus, there remain significant conflicting evidence and debate regarding the utility of GIK infusion in various patient populations. Extensive preclinical rationales support the use of GIK as an inotropic and metabolic therapy in several critical illnesses. The heart develops insulin resistance in shock and sepsis, and insulin-euglycemia produces a potent inotropic effect on the left ventricle. 5,6 Sepsis can lead to excessive phosphorylation of the pyruvate dehydrogenase complex, thus impairing net carbohydrate oxidation in skeletal and heart muscle. 7-9 Deficits in carbohydrate oxidation can be expected to be worsened by the effect of diabetes mellitus, a common comorbidity in humans. 10 Insulin reactivates th...

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Reversal of myocardial dysfunction in endotoxin shock with insulin

Cited by 16 publications

References 3 publications

The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart

The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart

Untitled

Effect of Glucose—Insulin—Potassium Infusion on Mortality in Critical Care Settings: A Systematic Review and Meta‐Analysis

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