A novel sodium-hydrogen exchanger isoform-1 inhibitor, zoniporide, reduces ischemic myocardial injury

The cardioprotective efficacy of zoniporide (CP-597,396), a novel, potent, and selective inhibitor of the sodium-hydrogen exchanger isoform 1 (NHE-1), was evaluated both in vitro and in vivo using rabbit models of myocardial ischemia-reperfusion injury. In these models, myocardial injury was elicited with 30 min of regional ischemia and 120 min of reperfusion. Zoniporide elicited a concentration-dependent reduction in infarct size (EC50 of 0.25 nM) in the isolated heart (Langendorff) and re-duced infarct size by 83 % (50 nM). This compound was 2.5- to 20-fold more potent than either eniporide or cariporide (EC50 of 0.69 and 5.11 nM, respectively), and reduced infarct size to a greater extent than eniporide (58 % reduction in infarct size). In open-chest, anesthetized rabbits, zoniporide also elicited a dose-dependent reduction in infarct size (ED50 of 0.45 mg/kg/h