These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Calcium sensitization in perfused beating guinea pig heart by a positive inotropic agent MCI-154.
    Author: Abe Y, Ishisu R, Onishi K, Sekioka K, Narimatsu A, Nakano T.
    Journal: J Pharmacol Exp Ther; 1996 Feb; 276(2):433-9. PubMed ID: 8632307.
    Abstract:
    We investigated the effects of MCI-154, a positive inotropic agent that increases the myofilament response to Ca++, on Ca++ transients, left ventricular (LV) function and phosphodiesterase (PDE) III activity of guinea pig heart, and compared them with the effects of pimobendan and milrinone. In Langendorff guinea pig hearts loaded with a fluorescent Ca++ probe indo-1, LV pressure and Ca++ transient were measured simultaneously. MCI-154 (10(-10)-10(-6) M) increased LV developed pressure, +dP/dt and -dP/dt with a reduction of LV end-diastolic pressure, although it did not affect coronary flow. The positive inotropic activity of MCI-154 was more potent than that of pimobendan and milrinone; EC50 values (concentrations for increasing +dP/dt by 50% from base line) were 4.31, 41.5 and 294 x 10(-9) M, respectively. The positive inotropic effect of MCI-154 was accompanied by the increase in systolic, diastolic and amplitude of indo-1 fluorescence ratio. The relative increase in Ca++ transients against the increase in LV contractility produced by MCI-154, however, was significantly less than that by increasing perfusate [Ca++], pimobendan or milrinone. MCI-154 (3 x 10(-7)-10(-4) M) inhibited the activity of PDE III isolated from guinea pig LV tissues, but the inhibitory effect of MCI-154 was less than pimobendan and milrinone; IC50 values were 10.1, 3.5 and 2.4 x 10(-6) M, respectively. These findings suggest that MCI-154 exerts a positive inotropic effect mainly through Ca(++)-sensitizing action in intact beating whole hearts.
    [Abstract] [Full Text] [Related] [New Search]