DISSOCIATION OF INTRACELLULAR SODIUM FROM CONTRACTILE STATE IN GUINEA-PIG HEARTS TREATED WITH OUABAIN

The positive inotropic effect of cardiac glycosides has been attribute d to inhibition of the Na-K-ATPase, accumulation of intracellular sodi um and enhanced calcium availability due to Na-Ca exchange. However. f ew measurements of intracellular sodium in the functioning left ventri cle following ouabain exposure at therapeutic doses are available. Our experimental objective was to quantitate the relationship between con tractile state and intracellular sodium measured by Na-23 nuclear magn etic resonance spectroscopy or atomic absorption in the intact heart. Isolated guinea-pig hearts, perfused in the Langendorff mode, were pac ed and then exposed to ouabain (3 x 10(-7) M) for 30 min. Left-ventric ular pressure was monitored continuously. Intracellular sodium was mea sured either at 1-min intervals throughout the perfusion by shift reag ent-aided Na-23 nuclear magnetic resonance spectroscopy in the beating heart or following 30 minutes of perfusion by atomic absorption in my ocardial tissue. While treatment with ouabain was associated with almo st a two-fold rise in developed pressure, there was no significant inc rease in intracellular sodium measured by either technique. Thus, the positive inotropic effect of ouabain in this model is not associated w ith significant changes in bull; intracellular sodium. However. these results do not exclude the possibility of shifts between intracellular pools which would not be detected in bulk measurements, or changes in NMR-invisible intracellular pools which are not detectable by single quantum spectroscopy techniques. (C) 1998 Academic Press Limited.