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 d uring Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletio n. With the use of Na-23 nuclear magnetic resonance, we previously obs erved a Ca2+ paradox without a prior Na+ increase. We have now demonst rated a Na+ increase during Ca2+ and Mg2+ depletion without the occurr ence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts we re perfused for 20 min with a Ca2+-free or a Ca2+- and Mg2+-free (Ca2/Mg2+-free) solution under hypothermic conditions (20 and 25 degrees 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 degrees C, whereas no significant change in [Na+](i) occurred durin g 20 min of Ca2+-free perfusion at 20 degrees C. In addition, we confi rmed that [Na+](i) did not change significantly during 20 min of normo thermic Ca2+-free perfusion. Creatine kinase release during normotherm ic Ca2+ repletion in the 20 degrees C groups was similar to 10% and in the 25 degrees C groups 75% of the release in the normothermia group. Recovery of rate-pressure product was similar to 50% in the 20 degree s C groups versus 0% in the normothermia group. In conclusion, hypothe rmic Ca2+/Mg2+-free perfusion results in a significant increase of[Na](i), which does not contribute to the extent of the Ca2+ paradox on n ormothermic Ca2+ repletion.