23Na NMR shift reagents enhance cardiac staircase effect in isolated perfused rat hearts

The effects of the currently used (23)Na NMR shift reagents, dysprosium bis-triphosphate [Dy(PPP)(2)], dysprosium triethylenetriamine hexaacetate [Dy(TTHA)] and thulium 1,4,7, 10-tetraazacyclododecane-N,N',N",N"'-tetra(methylenephosphonate) [Tm(DOTP)] were studied in the rat heart cardiac staircase model. Rat hearts were perfused with low or normal extracellular free calcium ([Ca(o)](f)). At low [Ca(o)](f) (0.34 +/- 0.05 mM), hearts were perfused with Dy(PPP)(2) (group I), Dy(TTHA) (group II) or no shift reagent (group III), while at normal [Ca(o)](f) (1.25 +/- 0.15 mM), hearts were perfused with Tm(DOTP) (group IV), Dy(TTHA) (group V) or no shift reagent (group VI). Left ventricular developed pressure (LVDP) values in group I were significantly higher than in groups II and III (p < 0.01), while no significant differences were found between groups II and III. LVDP values in group IV were significantly higher than in groups V and VI (p < 0.05), while the LVDP values in groups V and VI were almost identical. Also, a positive correlation between pacing rate and intracellular sodium ([Na(i)]) was evident. The [Na(i)] values at high [Ca(o)](f) were significantly lower than at low [Ca(o)](f) at each pacing level (p <0.01), indicating a negative correlation between [Na(i)] and [Ca(o)](f). No statistical differences were found in [Na(i)] between groups I vs II and IV vs V, showing that determination of [Na(i)] is not affected by any of these shift reagents. Thus the different LVDP responses in groups I vs II and IV vs V were not mirrored in [Na(i)] changes. We hypothesize that a direct, sarcolemmal Ca-Dy(PPP)(2)-, or Ca-Tm(DOTP)-induced positive inotropic effect could be responsible for these Na(i)-independent LVDP increases in groups I and IV.