Enhanced sensitivity of the failing human myocardium to cardiac glycosides and Na(+)-channel activators

American Heart Journal
R H SchwingerE Erdmann

Abstract

Cardiac glycosides and Na+ -channel activators increase intracellular Na+ and thereby enhance the transport rate of the sarcolemmal Na+/Ca2+ exchanger. We tested the hypothesis of whether increased expression of the Na+/Ca2+ exchanger in failing human myocardium is accompanied by enhanced sensitivity of the failing human myocardium toward cardiac glycosides and Na+ -channel activators. We studied the positive inotropic effects of the new Na+ -channel activator BDF and the cardiac glycoside ouabain in human failing (New York Heart Association [NYHA] functional class IV, heart transplants for dilated cardiomyopathy, n = 11) and nonfailing (donor hearts, n = 5) myocardium on electrically driven left ventricular papillary muscle strips (1 Hz, 37 degrees C). The effectiveness of ouabain and BDF to increase force of contraction was similar in human nonfailing and failing myocardium. BDF was more potent to increase force of contraction in failing than in nonfailing tissue (p < 0.05). The time until maximal inotropic effect developed after ouabain was significantly shorter in NYHA IV (mean 150 +/- 16 min) than in nonfailing myocardium (mean 240 +/- 20 min). These results suggest that human failing myocardium exerts and enhanced sensiti...Continue Reading

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Citations

Oct 1, 1996·The Journal of Clinical Investigation·J WangA A McDonough
May 29, 1998·Journal of Clinical Pharmacology·P R YasharW H Frishman
Mar 28, 2007·Heart Failure Clinics·Sian E Harding
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May 15, 2007·American Journal of Physiology. Cell Physiology·Wilhelm Schoner, Georgios Scheiner-Bobis
May 21, 1998·Journal of Cardiovascular Pharmacology·J Müller-EhmsenR H Schwinger
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Aug 4, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Lucía RomeroBlanca Rodríguez
Jul 17, 1999·Heart & Lung : the Journal of Critical Care·C M O'ConnorK Swedberg

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