Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis.

American Journal of Nephrology

PubMedID: 24994076

Wu D, Kraut JA. Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis. Am J Nephrol. 2014;40(1):36-42.
Background: Metabolic acidosis is associated with impaired cellular function. This has been attributed to the accompanying reduction in intracellular and interstitial pH of the myocardium. Recent studies suggest that activation of the cellular Na(+)-H(+) exchanger NHE1 might contribute to myocardial dysfunction. This review examines the experimental evidence which supports the role of NHE1 in the genesis of acidosis-induced cellular dysfunction, the benefits of its inhibition, and the type of acidosis that might benefit from therapy. Summary: Information was obtained by searching MEDLINE for articles published between 1969 and 2013 using the terms: NHE1, metabolic acidosis, lactic acidosis, ischemia-reperfusion, shock, resuscitation, high anion gap acidosis, and non-gap acidosis. Each article was also reviewed for additional suitable references. Nineteen manuscripts published between 2002 and 2013 assessed the impact of inhibition of NHE1 on cellular function. They revealed that NHE1 is activated with metabolic acidosis associated with hypoxia, hypoperfusion, hemorrhagic shock, and sepsis. This was associated with a rise in cellular sodium and calcium and cardiac dysfunction including reduced contractility and a predisposition to cardiac arrhythmias. Inhibition of NHE1 with specific inhibitors improved cardiac function, reduced blood and tissue levels of proinflammatory cytokines, and decreased mortality. Key Message: These results suggest that use of inhibitors of NHE1 might be worthwhile in the treatment of some types of acute metabolic acidosis, specifically the lactic acidosis associated with hypoxia, hemorrhagic shock, and cardiac arrest. Its potential role in the treatment of other forms of acute metabolic acidosis remains to be determined. © 2014 S. Karger AG, Basel.