Blockade of NHE with cariporide was cardioprotective and reduced end-ischemic intracellular Na+ overload to 184% of baseline compared to 320% in untreated hearts, whereas NBC blockade was not.
In isolated rat hearts, both NHE and NBC mediate Na+ influx during ischemia, but NHE blockade alone is cardioprotective whereas combined blockade impairs coronary flow.
Absolute Event Rate: 184% vs 320%
The Na(+)/H(+) exchanger (NHE) and/or the Na(+)/HCO(3)(-) cotransporter (NBC) were blocked during ischemia in isolated rat hearts. Intracellular Na(+) concentration (Na(+)(i)), intracellular pH (pH(i)), and energy-related phosphates were measured by using simultaneous (23)Na and (31)P NMR spectroscopy. Hearts were subjected to 30 min of global ischemia and 30 min of reperfusion. Cariporide (3 microM) or HCO(3)(-)-free HEPES buffer was used, respectively, to block NHE, NBC, or both. End-ischemic Na(+)(i) was 320 +/- 18% of baseline in HCO(3)(-)-perfused, untreated hearts, 184 +/- 6% of baseline when NHE was blocked, 253 +/- 19% of baseline when NBC was blocked, and 154 +/- 6% of baseline when both NHE and NBC were blocked. End-ischemic pH(i) was 6.09 +/- 0.06 in HCO(3)(-)-perfused, untreated hearts, 5.85 +/- 0.02 when NHE was blocked, 5.81 +/- 0.05 when NBC was blocked, and 5.70 +/- 0.01 when both NHE and NBC were blocked. NHE blockade was cardioprotective, but NBC blockade and combined blockade were not, the latter likely due to a reduction in coronary flow, because omission of HCO(3)(-) under conditions of NHE blockade severely impaired coronary flow. Combined blockade of NHE and NBC conserved intracellular H(+) load during reperfusion and led to massive Na(+) influx when blockades were lifted. Without blockade, both NHE and NBC mediate acid-equivalent efflux in exchange for Na(+) influx during ischemia, NHE much more than NBC. Blockade of either one does not affect the other.
Hove et al. (Fri,) conducted a other in Ischemia. Blockade of NHE (Cariporide) and/or NBC (HCO3(-)-free HEPES buffer) vs. HCO3(-)-perfused, untreated hearts was evaluated on End-ischemic intracellular Na+ concentration ([Na+]i) as % of baseline. Blockade of NHE with cariporide was cardioprotective and reduced end-ischemic intracellular Na+ overload to 184% of baseline compared to 320% in untreated hearts, whereas NBC blockade was not.
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