Activity of the Na+/H+ exchanger contributes to cardiac damage following ischaemia and reperfusion

1. The present review considers the evidence that Na+-H+ exchange activity contributes to cardiac damage following ischaemia and reperfusion, The basic mechanism involved is that protons are produced during ischaemia and leave the myocytes on the Na+/H+ exchanger during either ischaemia and/or reperfusion, The resulting elevation of [Na+](i) causes Ca2+ loading through the Na+/Ca2+ exchanger and the elevated [Ca2+](i) is thought to lead to myocardial damage, 2. Inhibition of the Na+/H+ exchanger during ischaemia and/or reperfusion produces a substantial cardioprotective effect by blocking the damage caused by the coupled exchanger mechanism described above. Preconditioning also produces a cardioprotective effect and the evidence that this also involves the Na+/H+ exchanger is reviewed, 3, The intracellular mechanisms associated with ischaemic damage and preconditioning are of great interest because they may provide targets for potential therapeutic interventions. The intracellular regulation of the Na+/H+ exchanger appears to be an important component of these pathways and may become a focus for therapeutic approaches.