Ions exchange during ischemia and reperfusion and consequence of inhibition of the NHE. Ischemia results in rapid intracellular acidosis as the metabolism becomes anaerobic, activating the pH-regulating ion transporters and the NHE. This results in a large influx of sodium (Na+) into the cell. As the ATP supply for the Na+/potassium (K+) pump falls, Na+ accumulates within the cell, reducing calcium (Ca2+) efflux and/or promoting reverse mode Ca2+ entry (3Na+/Ca2+). The exchange is self-limited as extracellular protons accumulate, but is reactivated upon reperfusion by the washout of the acidotic extracellular fluid, reactivating the NHE system for an accumulation of ions within the cell. NHE inhibition markedly reduces this Na+ and Ca2+ overload. H+, hydrogen.