Potential beneficial mechanisms of insulin (glucose-potassium) in acute myocardial infarction.

In the time-span of almost a century, a large amount of experimental evidence has been accumulated that underlines the importance of glucose metabolism during ischaemia/reperfusion of the heart. As early as 1912, Goulston suggested that treatment with glucose could be beneficial in several heart diseases. The first experimental results on the mechanical effects of insulin and glucose in the isolated heart were reported by Visscher and Muller in 1926. In 1935, Evans and colleagues showed that the uptake of glucose is increased in the ischaemic myocardium. Almost 30 years later, Sodi-Pallares and colleagues suggested that metabolic interference during myocardial ischaemia with GIK infusion decreased electrocardiographic signs of ischaemia. They also showed that glucose-insulin-potassium (GIK) infusion resulted in a lower occurrence of arrhythmias. They attributed this effect mainly to the influx of potassium in ischaemic cardiomyocytes. In order to further stimulate potassium transport into the cell, insulin was administered. Consequently, the rise of intercellular calcium is curtailed by the influx of potassium and so the incidence of arrhythmias is reduced. However, systemic infusion of insulin stimulates the uptake of glucose in many celltypes, which may result in hypoglycaemic episodes. Consequently, it is not possible to administer potassium and insulin in high concentrations without adding glucose. Interventions in the glucose metabolism in the clinical arena, whether or not used to correct acute hyperglycaemia, encompass three potentially effective elements: glucose, insulin and potassium.