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High intracellular Na+ preserves myocardial function at low heart rates in isolated myocardium from failing hearts.

Abstract
We investigated the hypothesis that increased intracellular [Na+]i in heart failure contributes to preservation of SR Ca2+ load which may become particularly evident at slow heart rates. [Na+]i in SBFI-loaded myocytes from rabbits with pacing-induced heart failure (PHF) was significantly higher at each frequency as compared to Sham-operated animals. Furthermore, PHF rabbits demonstrated reduced SR Ca2+-ATPase protein levels (-37%, p < 0.04) but unchanged Na+/Ca2+ exchanger protein levels. At 0.25 Hz, isometric force was similar in cardiac trabeculae from PHF rabbits as compared to control (PHF, 3.6+/-1.3; Sham, 4.4+/-0.6 mN/mm2). Rapid cooling contractures (RCCs) were unchanged indicating preserved SR Ca2+ load at this frequency. In Sham, isometric twitch force increased with rising frequencies to 29.0+/-2.8 mN/mm2 at 3.0 Hz (p < 0.05) as compared to 0.25 Hz. RCCs showed a parallel increase by 186+/-47% (p < 0.01). In PHF, frequency-dependent increase in force (15.8+/-4.7 mN/mm2 at 3.0 Hz) and RCCs (increase by 70+/-40%) were significantly blunted. Thus, in PHF in rabbits SR Ca2+ load is preserved at low frequencies despite decreased SR Ca2+-ATPase expression. This may result from [Na+]i-dependent changes in Na+/Ca2+ exchanger activity.
AuthorsWolfgang Schillinger, Nils Teucher, Claus Christians, Michael Kohlhaas, Samuel Sossalla, Phuc Van Nguyen, Albrecht G Schmidt, Ortwin Schunck, Klaus Nebendahl, Lars S Maier, Oliver Zeitz, Gerd Hasenfuss
JournalEuropean journal of heart failure (Eur J Heart Fail) Vol. 8 Issue 7 Pg. 673-80 (Nov 2006) ISSN: 1388-9842 [Print] England
PMID16540370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Sodium-Calcium Exchanger
  • Sodium
  • Calcium-Transporting ATPases
Topics
  • Animals
  • Calcium-Transporting ATPases (metabolism)
  • Disease Models, Animal
  • Electric Stimulation
  • Heart Failure (metabolism)
  • Muscle Cells
  • Rabbits
  • Sarcoplasmic Reticulum (metabolism)
  • Sodium (metabolism)
  • Sodium-Calcium Exchanger

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