Role of the cardiac Na+/H+ exchanger during ischemia and reperfusion.
The coupled exchanger theory describes one of the central mechanisms of damage in the ischemic heart. The theory proposes that anaerobic glycolysis produces lactate and protons and that the protons can leave the cardiac cell on the cardiac Na+/H+ exchanger (NHE1). The subsequent rise in [Na+]i stimulates the cardiac Na+/Ca2+ exchanger (NCX) and results in an increase in [Ca2+]i which promotes myocardial cell damage. Although the general features of this theory are widely accepted, there is dispute about some aspects, specifically whether the NHE1 remains active during ischemia or not. We review the evidence on this issue and conclude that NHE1 is substantially inhibited during ischemia. This issue is central to the design of a clinical trial of NHE1 inhibitors in the treatment of human cardiac ischemia and the existing clinical trials are considered in this light.
Allen
David G
DG
Department of Physiology and Institute for Biomedical Research, University of Sydney F13, NSW 2006, Sydney, Australia. davida@physiol.usyd.edu.au <davida@physiol.usyd.edu.au>
Xiao
Xiao-Hui
XH
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D012964:Sodium / Q000032:analysis; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium