Milrinone enhances cytosolic calcium transient and contraction in rat cardiac myocytes during beta-adrenergic stimulation

Stefano Raffaeli, Claudio Ferroni, Harold A. Spurgeon, Maurizio C. Capogrossi

Research output: Contribution to journalArticlepeer-review


We have investigated the mechanism that underlies the absence of a positive inotropic effect of milrinone on rat myocardium. The twitch characteristics of enzymatically dissociated left ventricular myocytes from the adult rat and guinea pig were assessed by edge tracking during field stimulation. In some rat myocytes loaded with the ester derivative of the Ca2+ probe Indo-1 we simultaneously measured changes in cell length and in the associated cytosolic Ca2+ (Ca1) transient. Our results show that in guinea pig myocytes bathed in 0.5 mM [Ca2+] and field stimulated at 1 Hz, milrinone (10 μM) had a positive inotropic effect. In contrast milrinone had no effect on the contractile properties of rat myocytes studied under similar conditions and field stimulated at 0.2 Hz. In rat myocytes bathed in 0.5 mM [Ca2+] and stimulated at 0.2 Hz isoproterenol (1 nM) increased the amplitude and shortened the duration of the contraction and of the associated Cai transient; these effects of beta-adrenergic stimulation were further enhanced by the addition of milrinone (10 μM) in the presence of isoproterenol. Under conditions of higher cell Ca2+ loading achieved by raising bathing [Ca2+] to 1 mM and isoproterenol to 3 nM the positive inotropic effect of milrinone (10 μM) in rat myocytes saturated when spontaneous oscillatory Ca2+ release appeared in the diastolic intervals between electrically stimulated twitches. Our results suggest that an enhancement in the baseline beta-adrenergic stimulation is required for milrinone to exercise a positive inotropic action on rat myocardial tissue.

Original languageEnglish
JournalInternational Journal of Cardiology
Issue numberSUPPL. 1
Publication statusPublished - 1989


  • Cardiac myocyte
  • Cardiotonic drug
  • Inotropic agent
  • Milrinone
  • Phosphodiesterase inhibitor
  • Spontaneous Ca release
  • β-Adrenergic stimulation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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