Positive inotropic action of amrinone: Effect of elevated external Ca2+

S. V. Rendig, Ezra A Amsterdam

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Abstract

To investigate the positive inotropic effect of amrinone under conditions of maximal contractile stimulation, we compared cumulative amrinone one-half log dose-response curves (dose range, 3.1 x 10-5-3.1 x 10-3 M amrinone) of isolated cat right ventricular papillary muscle in normal (2.5 mM) and high (7.5 mM) calcium Krebs solution. In 2.5 mM calcium, amrinone induced significant (p < 0.01) dose-dependent increases in peak developed tension (T), maximum dT/dt, and maximum relaxation rate (-dT/dt), whicn were accompanied by small but significant decreases in time-to-peak tension (TTP). At 10-3 M, changes in T, dT/dt, and TTP were 61.9 (2.7 g/mm2), 98.1 (33.2 g/s/mm2), and -13.1% (-26 ms), respectively. In 7.5 mM calcium, the increases in T, dT/dt, and -dT/dt, and the reduction of TTP, were markedly less at each concentration. At 10-3M amrinone, T and dT/dt increased significantly by 16.7 (1.3 g/mm2) and 23.5% (17.4 g/s/mm2), respectively, with no change in TTP. The amrinone-induced reductions in one-half relaxation time and twitch duration persisted in high calcium and were similar in magnitude to those in 2.5 mM calcium. The substantial reduction of amrinone's positive inotropic effect in high Ca2+ suggests that a major part of the drug's action involves an augmentation of contractile Ca2+. An amrinone-induced effect on rate of Ca2+ delivery to the contractile apparatus or on myofilament Ca2+ sensitivity would be consistent with a persistent inotropic action in high Ca2+. Contractile changes induced by amrinone are discussed in relation to a possible effect on intracellular cyclic AMP levels.

Original languageEnglish (US)
Pages (from-to)293-299
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume6
Issue number2
StatePublished - 1984

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Amrinone
Calcium
Papillary Muscles
Myofibrils
Cyclic AMP
Cats

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Positive inotropic action of amrinone : Effect of elevated external Ca2+. / Rendig, S. V.; Amsterdam, Ezra A.

In: Journal of Cardiovascular Pharmacology, Vol. 6, No. 2, 1984, p. 293-299.

Research output: Contribution to journalArticle

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abstract = "To investigate the positive inotropic effect of amrinone under conditions of maximal contractile stimulation, we compared cumulative amrinone one-half log dose-response curves (dose range, 3.1 x 10-5-3.1 x 10-3 M amrinone) of isolated cat right ventricular papillary muscle in normal (2.5 mM) and high (7.5 mM) calcium Krebs solution. In 2.5 mM calcium, amrinone induced significant (p < 0.01) dose-dependent increases in peak developed tension (T), maximum dT/dt, and maximum relaxation rate (-dT/dt), whicn were accompanied by small but significant decreases in time-to-peak tension (TTP). At 10-3 M, changes in T, dT/dt, and TTP were 61.9 (2.7 g/mm2), 98.1 (33.2 g/s/mm2), and -13.1{\%} (-26 ms), respectively. In 7.5 mM calcium, the increases in T, dT/dt, and -dT/dt, and the reduction of TTP, were markedly less at each concentration. At 10-3M amrinone, T and dT/dt increased significantly by 16.7 (1.3 g/mm2) and 23.5{\%} (17.4 g/s/mm2), respectively, with no change in TTP. The amrinone-induced reductions in one-half relaxation time and twitch duration persisted in high calcium and were similar in magnitude to those in 2.5 mM calcium. The substantial reduction of amrinone's positive inotropic effect in high Ca2+ suggests that a major part of the drug's action involves an augmentation of contractile Ca2+. An amrinone-induced effect on rate of Ca2+ delivery to the contractile apparatus or on myofilament Ca2+ sensitivity would be consistent with a persistent inotropic action in high Ca2+. Contractile changes induced by amrinone are discussed in relation to a possible effect on intracellular cyclic AMP levels.",
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