Na+ entry during ischemia, reperfusion and preconditioning

Abstract

In our recent series of papers [1–3] we have measured intracellular sodium and pH ([Na+]i and pHi) in rat hearts during ischemia and reperfusion and draw the following conclusions about the activity of the cardiac Na+/H+ exchanger (NHE1). (i) NHE1 is inactive during ischemia. (ii) Normally NHE1 reactivates rapidly on reperfusion causing a large Na+ influx which is the precursor to much of the cellular damage. (iii) However in the preconditioned heart NHE1 remains inactive during early reperfusion and this underlies much of the protective effects of preconditioning. Our evidence and interpretation are different to many earlier studies, as Avkiran et al. [4] point out, and we are pleased to have this opportunity to debate the reasons for these differences and consider the implications of our novel interpretation. We would first like to comment on the statement by Avkiran et al. ‘Much of this evidence, which suggests that NHE activity is sustained during ischemia…., has not been acknowledged by Xiao & Allen [3]’. In our paper we stated ‘… there is dispute about the extent to which Na+ entry occurs during ischemia…. Recent reviews by Murphy [5] and Karmazyn [6] discuss this evidence in detail and support the view that Na+ entry during ischemia by NHE1 is important…’ Thus we believe we have appropriately referenced alternative view points. Our perspective, as holders of a minority view point, is that the majority view represented by Avkiran et al. has been widely promulgated in a series of reviews [5–9] and a more serious difficulty in the field is for alternative view points to receive appropriate attention. One crucial issue is whether or not the NHE1 is active during ischemia and the extent of the contribution of NHE1 to the rise of …