title: 23Na NMR shift reagents enhance cardiac staircase effect in isolated perfused rat hearts.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, and the Center for Nuclear Imaging Research, AL 35294, USA.
authors.forename: T
authors.initials: T
authors.lastname: Simor
authors.forename: T
authors.initials: T
authors.lastname: Lóránd
authors.forename: A
authors.initials: A
authors.lastname: Szöllösy
authors.forename: B
authors.initials: B
authors.lastname: Gaszner
authors.forename: S B
authors.initials: SB
authors.lastname: Digerness
authors.forename: G A
authors.initials: GA
authors.lastname: Elgavish
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004419:Dysprosium / Q000494:pharmacology*; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007202:Indicators and Reagents; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010477:Perfusion; D011122:Polyphosphates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012979:Sodium Radioisotopes; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D007202:Indicators and Reagents; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011122:Polyphosphates; D012979:Sodium Radioisotopes; C069929:thulium(III) 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate; D004419:Dysprosium; C048543:bis(tripolyphosphate)dysprosium(III); C026059:triethylenetetraminehexaacetic acid; D004492:Edetic Acid; D002118:Calcium