Effects of a novel inotropic agent, bay y 5959, in conscious dogs
--- comparison with dobutamine and milrinone.
Sato, Naoki, Masami Uechi, Kuniya Asai, Thomas Patrick, Raymond K.
Kudej, and Stephen F. Vatner.
Department of Medicine, Harvard Medical School, Brigham &
Women's Hospital, Boston, MA 02115 and the New England Regional
Primate Research Center, Southborough, MA 01772
APStracts 3:0373H, 1996.
Traditional inotropic agents, e.g., those that increase myocardial
contraction through enhanced cyclic AMP or those that increase
contractility at relatively high O2 cost are frequently not useful in
the clinical setting. Accordingly, newer agents that operate through
different mechanisms have been synthesized. The goal of the present
study was to compare the effects of a new calcium promotor, BAY y
5959, with more traditional inotropic agents, dobutamine (DOB) and
milrinone (MIL) in 11 conscious dogs, chronically instrumented for
measurement of left ventricular (LV) and arterial pressures, LV
internal diameter, wall thickness, coronary blood flow, and arterial
and coronary sinus oxygen. Equi-inotropic doses of BAY y 5959, DOB
and MIL were selected, i.e., BAY y 5959 (20[mu]g/kg/min), DOB
(10[mu]g/kg/min), and MIL (10[mu]g/kg/min), which increased LV dP/dt
in sinus rhythm by 71-78% from similar baselines. Heart rate rose
with DOB (+244%) and MIL (+232%), but fell with BAY y 5959 (-353%).
DOB increased MVo2 by 8810%. In contrast, MVo2 increased less,
p<0.05, with BAY y 5959 (+93%) and MIL (+165%). Furthermore,
mechanical efficiency was also calculated using either direct
measurement of cardiac output or pressure-volume loops. DOB and MIL
did not change efficiency; however BAY y 5959 increased efficiency by
195%. With heart rate held constant, BAY y 5959 increased MVo2 by
324%, but still increased efficiency by 287%. Thus, the calcium
promotor, BAY y 5959, has unique features that might be desirable for
clinical applications where inotropic support is indicated, but
increased MVo2 without enhanced mechanical efficiency is deleterious.
Received 27 June 1996; accepted in final form 13 August 1996.
APS Manuscript Number H573-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996