Preconditioning and metabolic anti-ischaemic agents

Preconditioning a powerful protective mechanism, is the response to transient ischemia and reperfusion. However, the best way to achieve total protection is to avoid ischemia altogether. Therefore prevention of ischemia and protection by preconditioning are differently mediated so that anti-ischemic agents may not precondition, whereas paradoxically pro-ischemic agents may precondition. Metabolically active agents such as glucose-insulin-potassium, trimetazidine and ranolazine that protect from ischemia, increase glucose metabolism relative to that of fatty acids. By promoting glycolysis they tend to close the ATP-dependent potassium channels that help to mediate preconditioning. By lessening the oxygen-wasting effects of fatty acids, they are mitochondrial protective and oxygen-sparing. These qualities should help in the therapy of myocardial ischemia and also heart failure.