Relative contributions of Na+/H+ exchange and Na+/HCO-3 cotransport to ischemic Nai+ overload in isolated rat hearts

• Published in: American journal of physiology. Heart and circulatory physiology 2005-01, Vol.57 (1), p.H287
• Main Authors: Michiel Ten Hove, Nederhoff, Marcel G J, Cees J A Van Echteld
• Format: Article
• Language: English
• Subjects: Heart; NMR; Nuclear magnetic resonance; Pulmonary arteries
• ISSN: 0363-6135; 1522-1539

The Na+/H+ exchanger (NHE) and/or the Na+/HCO3 cotransporter (NBC) were blocked during ischemia in isolated rat hearts. Intracellular Na+ concentration ([Na+]i), intracellular pH (pHi), and energy-related phosphates were measured by using simultaneous 23Na and 31P NMR spectroscopy. Hearts were subjected to 30 min of global ischemia and 30 min of reperfusion. Cariporide (3 mM) or HCO3-free HEPES buffer was used, respectively, to block NHE, NBC, or both. End-ischemic [Na+]i was 320 plus or minus 18% of baseline in HCO3-perfused, untreated hearts, 184 plus or minus 6% of baseline when NHE was blocked, 253 plus or minus 19% of baseline when NBC was blocked, and 154 plus or minus 6% of baseline when both NHE and NBC were blocked. End-ischemic pHi was 6.09 plus or minus 0.06 in HCO3-perfused, untreated hearts, 5.85 plus or minus 0.02 when NHE was blocked, 5.81 plus or minus 0.05 when NBC was blocked, and 5.70 plus or minus 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 HCO3 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. [PUBLICATION ABSTRACT]