Glucose, insulin, potassium (GIK) and the concept of metabolic support for the postischaemic heart

Abstract

Successful reperfusion has moved the frontier of treatment for acute myocardial ischaemia from coronary arteries to the heart muscle itself. Here we update the concept of metabolic support for the postischaemic heart which is based on an understanding of an earlier review on the same topic. The ischaemic heart is an energy-depleted organ. A mismatch of ATP production and utilisation leads to the uncoupling of ATP-dependent Ca²⁺-mediated excitation-contraction coupling necessary for normal contractile function. Sustained ischaemia leads to adaptive changes of either programed cell survival, cell death or cell necrosis. We are presenting a working hypothesis on the metabolic and ionic consequences of myocardial ischaemia that lead to progressive contractile dysfunction. Based on this hypothesis we develop a rationale for the use of GIK in the support of substrate metabolism by replenishing depleted energy stores to reverse the deleterious events in the postischaemic state. Possible mechanisms include replenishment of depleted cellular glycogen stores and restoration of efficient energy transfer through moiety-conserved cycles. The usefulness of this concept has been demonstrated in the improved survival of patients in cardiogenic shock after hypothermic ischaemic arrest of the heart and in patients with acute myocardial infarction treated with GIK.