An increase in intracellular [Na+] during Ca2+ depletion is not related to Ca2+ paradox damage in rat hearts

Ca2+paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+ depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts were perfused for 20 min with a Ca2+-free or a Ca2+- and Mg2+-free (Ca2+/Mg2+-free) solution under hypothermic conditions (20 and 25°C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 ± 1.2 to 26.9 ± 5.8 mM ( P < 0.001) during Ca2+/Mg2+-free perfusion at 20°C, whereas no significant change in [Na+]ioccurred during 20 min of Ca2+-free perfusion at 20°C. In addition, we confirmed that [Na+]idid not change significantly during 20 min of normothermic Ca2+-free perfusion. Creatine kinase release during normothermic Ca2+ repletion in the 20°C groups was ∼10% and in the 25°C groups 75% of the release in the normothermia group. Recovery of rate-pressure product was ∼50% in the 20°C groups versus 0% in the normothermia group. In conclusion, hypothermic Ca2+/Mg2+-free perfusion results in a significant increase of [Na+]i, which does not contribute to the extent of the Ca2+ paradox on normothermic Ca2+ repletion.