Abstract
The hypothesis that sarcolemmal Na+/H+ exchanger activity may contribute to myocardial injury during ischemia and reperfusion was first published in 1985,1 preceding by 1 year the first description of the ischemic preconditioning phenomenon.2 Initial pharmacological evidence in support of the Na+/H+ exchanger hypothesis was subsequently provided by Karmazyn,3 who showed that amiloride (an inhibitor of the exchanger) enhanced the postischemic recovery of contractile function and reduced creatine kinase leakage in rat hearts subjected to global ischemia and reperfusion. Since then, a number of Na+/H+ exchange inhibitors, including highly specific novel inhibitors such as HOE-694, HOE-642 (cariporide), and EMD-85131, have been shown to afford cardioprotective benefit in a variety of animal models of ischemia and reperfusion.4 Nevertheless, as an innovative approach to the protection of ischemic myocardium, Na+/H+ exchange inhibition has failed to capture the imagination of cardiologists (experimental and clinical alike) to quite the same extent as ischemic preconditioning. Indeed, a survey of articles published in Circulation and Circulation Research over the past decade reveals only 14 articles whose title or abstract contains the keywords “Na+/H+ exchange(r) and ischemia,” whereas 115 articles are identified when the combination “preconditioning and ischemia” is used. Is this a fair reflection of the relative cardioprotective efficacy, and perhaps the therapeutic potential, of these interventions? In this issue of Circulation , Gumina and colleagues5 report on a comparison of the efficacy of Na+/H+ exchange inhibition (achieved with BIIB-513, the latest addition to the family of novel Na+/H+ exchange inhibitors) versus ischemic preconditioning in limiting infarct size in dog hearts subjected to regional ischemia and reperfusion in vivo. This is the first such comparison in a large animal, and the …
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