الفهرس 
Pathophysiology of inflammation and ischemia reperfusionOnly 14 pages are availabe for public view
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Abstract
Use of combined infusions of glucose, insulin, and potassium (GIK) was introduced for the perioperative management of the diabetic patient. Subsequently, considerable attention has been given to the pharmacologic use of insulin as an anabolic agent in non-diabetic patients with the intention of ameliorating protein losses after trauma and surgery.
Much data has accumulated showing that GIK administration can limit the ischemic myocardial damage after acute myocardial infarction as reflected in improved cardiac output, stroke volume, mean arterial pressure, and oxygen consumption. and reduced morbidity and mortality. Therefore, the option of GIK treatment has been incorporated into the guidelines for the management of patients with acute myocardial infarction. But showed that Insulin but not the glucose or potassium that is responsible for the observed improvement in cardiac function.
Prospective, randomized, controlled study involving adults admitted to surgical intensive care units and receiving mechanical ventilation, intensive insulin therapy substantially reduced mortality and morbidity. Intensive insulin
treatment reduced the number of deaths from multiple organ failure with sepsis. Markers of inflammation were found to be less frequently abnormal in the intensive insulin treatment group than in the conventional treatment group, although the nature of the inflammatory markers measured was not given.
The preserving influence of GIK infusions on the ischemic myocardium is not a new phenomenon. Originally GIK administration has long been known to increase the intracellular cardiac glycogen content and enhance resistance to ischemia caused by enhanced glycolytic and anaerobic ATP production. GIK treatment also is accompanied by a decrease in circulating concentrations of free fatty acids, which has deleterious effects on myocardial function and metabolism during ischemia.
The results of post-operative cardiac surgery meta-analysis confirmed that GIK was associated with reduced myocardial injury and better postoperative hemodynamic performance in cardiac surgery patients, as compared with control.
The American College of Cardiology/American Heart Association (ACC/AHA) guideline has recommended that blood glucose concentration should be controlled in surgical patients during the perioperative period.Conducting a subgroup analysis based on different aims of GIK therapy and both groups were beneficial for patients undergoing cardiac surgery. Further analysis demonstrated that in these trials that have included diabetics, patients were benefited from glycemic control, but not GIK infusion without glucose control. These results suggest that GIK without glycemic control was ineffective in diabetic patients, and this might explain the discrepancy seen regarding the beneficial effects of GIK in earlier studies.
Glucose Insulin in Stroke Trial sought to assess the effectiveness of glucose modulation with insulin in acute stroke. Despite repeated observations of an association between hyperglycaemia and stroke outcome, the study found no beneficial effect for GIK treatment on the primary and secondary outcomes, as outlined in the trial protocol. Furthermore, there was no evidence for benefit in any of the subgroups represented by the prespecified stratification variables.
One must not forget the fact that there is a strong relationship between acute changes in plasma glucose homeostasis and the immune system. It is further hypothesized that the use of GIK would be effective in the treatment of a variety of other inflammatory diseases where cytokines play major pathogenic roles such as intersititial pneumonitis, chronic inflammatory bowel disease, rheumatoid arthritis, systemic sclerosis and Alzheimer’s disease.
Over the past decades, the results of numerous clinical studies using GIK or glucose-insulin for the treatment of acute myocardial infarction have varied remarkably, more so than the numerous positive preclinical studies. At the present time, GIK cannot be recommended as standard adjunctive treatment with reperfusion. In retrospect, certain factors may explain the negative results of several of the trials and make it difficult to compare the results of the trials. GIK was typically used in many of the clinical trials as a fixed-dose cocktail without adjustments in the amount of intravenous volume or glucose administered. GIK in some patients could paradoxically increase mortality by raising glucose levels or causing volume overload early in the course of myocardial injury.
Future researchers can contribute to the data base if they will perform pre-prandial testing of serum insulin before, during, after treatment. Studies establish correct doses, duration of treatment and method of administration, but one of the advantages of GIK is that it is not a new drug. Clinicians are familiar with the signs of toxicity and counter-measures.