Glucose and glycogen utilisation in myocardial ischemia--changes in metabolism and consequences for the myocyte.
Experimentally, enhanced glycolytic flux has been shown to confer many benefits to the ischemic heart, including maintenance of membrane activity, inhibition of contracture, reduced arrhythmias, and improved functional recovery. While at moderate low coronary flows, the benefits of glycolysis appear extensive, the controversy arises at very low flow rates, in the absence of flow; or when glycolytic substrate may be present in excess, such that high glucose concentrations with or without insulin overload the cell with deleterious metabolites. Under conditions of total global ischemia, glycogen is the only substrate for glycolytic flux. Glycogenolysis may only be protective until the accumulation of metabolites (lactate, H+, NADH, sugar phosphates and Pi ) outweighs the benefit of the ATP produced. The possible deleterious effects associated with increased glycolysis cannot be ignored, and may explain some of the controversial findings reported in the literature. However, an optimal balance between the rate of ATP production and rate of accumulation of metabolites (determined by the glycolytic flux rate and the rate of coronary washout), may ensure optimal recovery. In addition, the effects of glucose utilisation must be distinguished from those of glycogen, differences which may be explained by functional compartmentation within the cell.
King
L M
LM
MRC/UCT Ischaemic Heart Disease Research Unit, UCT Medical School, Cape Town, South Africa.
Opie
L H
LH
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
D006003:Glycogen; D005947:Glucose