SLC9A1 and ischemia: The debate over the mechanistic basis for this failure has centered around the timing of NHE1 inhibitor therapy, with two main hypotheses: that NHE1 inhibition needs to occur during ischemia (rather than just during reperfusion); and/or that inhibition during reperfusion is beneficial but that the timing of NHE1 inhibitor therapy did not allow for the drug to access the affected tissue immediately at the onset of reperfusion [5].