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Positive inotropic effects of calcium sensitizers on normal and failing cardiac myocytes.

Abstract
Calcium sensitizers increase myocardial contractile function without affecting Ca2+ homeostasis, which might be beneficial in the treatment of patients with heart failure. However, it remains uncertain whether Ca sensitizers induce quantitatively similar inotropic responses in control and failing hearts. To compare their effects in normal versus failing hearts at the cellular level, shortening mechanics and intracellular calcium ([Ca2+]i) transient were simultaneously measured in the left ventricular myocytes isolated from normal dogs (n = 8) and dogs with rapid pacing-induced heart failure (n = 7). CGP 48506 and EMD 57033 exerted a positive inotropic effect in a dose (0.1-3 microM)-dependent manner in both normal and heart failure myocytes. The percent increase of cell shortening magnitude was comparable between the two groups. CGP 48506 and EMD 57033 did not affect the diastolic cell length and resting [Ca2+]i level. They did not affect the duration of [Ca2+]i transient dynamics. Thus Ca2+ sensitizers exerted comparable positive inotropic effects without affecting the rest cell length and rest [Ca2+]i in normal and heart failure myocytes.
AuthorsH Tsutsui, S Kinugawa, T Ide, S Hayashidani, N Suematsu, S Satoh, R Nakamura, K Egashira, A Takeshita
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 37 Issue 1 Pg. 16-24 (Jan 2001) ISSN: 0160-2446 [Print] United States
PMID11152370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Azocines
  • Cardiotonic Agents
  • Quinolines
  • Thiadiazines
  • EMD 53998
  • BA 41899
  • Calcium
Topics
  • Animals
  • Azocines (pharmacology)
  • Calcium (metabolism)
  • Cardiac Pacing, Artificial
  • Cardiotonic Agents (pharmacology)
  • Dogs
  • Myocardial Contraction (drug effects, physiology)
  • Quinolines (pharmacology)
  • Stimulation, Chemical
  • Thiadiazines (pharmacology)
  • Ventricular Function, Left (drug effects, physiology)

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