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

The effects of the currently used Na-23 NMR shift reagents, dysprosium bis- triphosphate [Dy(PPP)(2)], dysprosium triethylenetriamine hexaacetate [Dy(T THA)] and thulium 1,4,7,10-tetraazacyclododecane-N,N',N ",N'''-tetra(methyl enephosphonate) [Tm(DOTP)] were studied in the rat heart cardiac staircase model. Rat hearts were perfused with low or normal extracellular free calci um ([Ca-o](f)). At low [Ca-o](f) (0.34 +/- 0.05 mM), hearts were perfused w ith Dy(PPP)(2) (group I), Dy(TTHA) (group II) or no shift reagent (group II I), 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). Le ft ventricular developed pressure (LVDP) values in group I were significant ly higher than in groups II and III (p < 0.01), while no significant differ ences were found between groups II and III. LVDP values in group IV were si gnificantly higher than in groups V and VI (p < 0.05), while the LVDP value s in groups V and VI were almost identical. Also, a positive correlation be tween 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 aff ected 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 hypothes ize that a direct, sarcolemmal Ca-Dy(PPP)(2)-, or Ca-Tm(DOTP)-induced posit ive inotropic effect could be responsible for these Nai-independent LVDP in creases in groups I and IV. Copyright (C) 1999 John Wiley & Sons, Ltd.