Background physiology

The use of GIK to improve ischaemic cardiac dysfunction has been based on two principles. First, insulin stimulates myocardial Na⁺ K⁺ ATPase, increasing reuptake of K⁺, stabilising the cell membrane, and reducing the incidence of dysrrhythmias. Second, insulin stimulates the myocardial uptake of glucose, increasing the provision of intracellular substrate. However the significance of the relatively small increase in ATP, which GIK produces by enhancing anaerobic oxidation of glucose, has been questioned. The evidence for attenuation of ischaemia induced reduction in ATP stores is scanty. Nevertheless, recent work suggests that the position of the glycolytic enzymes within the cell may ensure that the little ATP that is produced is situated in regions critical to the maintenance of cellular membrane functions such as calcium and sodium homeostasis.2 Provision of a high glucose substrate protects myocytes from the toxic effects of the increase in intracellular calcium induced by ischaemia.3 Previous concerns that during ischaemia these benefits may be limited by the generation of inhibitors of glycolysis, such as lactate, have been allayed by recent studies of myocardial infarction showing that the infarct area is a region of low flow, not zero flow, sufficient to deliver substrate and remove lactate. This provides a rationale for the use of GIK in acute ischaemia.

Other metabolic effects of ischaemia are also important, not least the increased production of catecholamines which leads to glucose intolerance and increased …