### 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/mm^{2}), 98.1 (33.2 g/s/mm^{2}), 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^{-3}M amrinone, T and dT/dt increased significantly by 16.7 (1.3 g/mm^{2}) and 23.5% (17.4 g/s/mm^{2}), 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 Ca^{2+} suggests that a major part of the drug's action involves an augmentation of contractile Ca^{2+}. An amrinone-induced effect on rate of Ca^{2+} delivery to the contractile apparatus or on myofilament Ca^{2+} sensitivity would be consistent with a persistent inotropic action in high Ca^{2+}. Contractile changes induced by amrinone are discussed in relation to a possible effect on intracellular cyclic AMP levels.

Original language | English (US) |
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Pages (from-to) | 293-299 |

Number of pages | 7 |

Journal | Journal of Cardiovascular Pharmacology |

Volume | 6 |

Issue number | 2 |

State | Published - 1984 |

### ASJC Scopus subject areas

- Pharmacology
- Cardiology and Cardiovascular Medicine

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## Cite this

^{2+}.

*Journal of Cardiovascular Pharmacology*,

*6*(2), 293-299.