Dissociation of intracellular sodium from contractile state in guinea-pig hearts treated with ouabain.
The positive inotropic effect of cardiac glycosides has been attributed to inhibition of the Na-K-ATPase, accumulation of intracellular sodium and enhanced calcium availability due to Na-Ca exchange. However, few measurements of intracellular sodium in the functioning left ventricle following ouabain exposure at therapeutic doses are available. Our experimental objective was to quantitate the relationship between contractile state and intracellular sodium measured by 23Na nuclear magnetic resonance spectroscopy or atomic absorption in the intact heart. Isolated guinea-pig hearts, perfused in the Langendorff mode, were paced and then exposed to ouabain (3x10(-7)m) for 30 min. Left-ventricular pressure was monitored continuously. Intracellular sodium was measured either at 1-min intervals throughout the perfusion by shift reagent-aided 23Na nuclear magnetic resonance spectroscopy in the beating heart or following 30 minutes of perfusion by atomic absorption in myocardial tissue. While treatment with ouabain was associated with almost a two-fold rise in developed pressure, there was no significant increase in intracellular sodium measured by either technique. Thus, the positive inotropic effect of ouabain in this model is not associated with significant changes in bulk 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.
Radford
N B
NB
University of Texas Southwestern Medical Center at Dallas, USA.
Makos
J D
JD
Ramasamy
R
R
Sherry
A D
AD
Malloy
C R
CR
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D010477:Perfusion; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase