Na+/H+ exchange inhibitors afford cardioprotective benefit only when present before ischemia onset and followed by timely reperfusion, such as during coronary artery bypass graft surgery.
Do Na+/H+ exchange inhibitors provide cardioprotective therapy in patients with evolving MI or at risk of MI?
NHE inhibitors may provide cardioprotective benefits if administered before or early during ischemia followed by timely reperfusion, highlighting their potential utility in settings like cardiac surgery.
Extensive pre-clinical work indicates that inhibition of the sarcolemmal Na(+)/H(+) exchanger (NHE) affords significant protection to myocardium subjected to ischemia and reperfusion, predominantly through reduced intracellular accumulation of Na(+) and consequently Ca(2+). In contrast, recent clinical studies with the NHE inhibitors cariporide and eniporide in patients with evolving myocardial infarction (MI) and those at risk of MI have provided mixed and somewhat contradictory data. The experimental evidence suggests that the key mechanism through which NHE inhibitors afford protection consists in slowing the progression of myocardial injury during ischemia and thereby enhancing myocardial salvage by reperfusion. It follows from this that, to obtain maximum cardioprotective benefit, 1) the NHE inhibitor must be present in jeopardized myocardium, at a concentration sufficient to inhibit NHE activity, before (or as soon as possible after) the onset of ischemia, and 2) ischemia must be terminated by timely reperfusion. Thus, in the GUARDIAN trial, the cardioprotective efficacy of cariporide was limited to the subset of high-risk patients who underwent coronary artery bypass graft surgery, in whom both prerequisites could be readily fulfilled. In contrast, no cardioprotective benefit was observed in the ESCAMI trial, in which eniporide was administered late as an adjunct to reperfusion therapy in patients with evolving MI. Ongoing clinical studies will determine whether NHE inhibition will find therapeutic application in the setting of cardiac surgery, while pre-clinical investigations continue to test the potential of NHE inhibitors in the treatment of other cardiovascular diseases such as heart failure.
Avkiran et al. (Fri,) conducted a review in Myocardial infarction and ischemia-reperfusion injury. Na+/H+ exchange inhibitors (cariporide, eniporide) was evaluated. Na+/H+ exchange inhibitors afford cardioprotective benefit only when present before ischemia onset and followed by timely reperfusion, such as during coronary artery bypass graft surgery.