Functional and energetic effects of the inotropic agents emd 57033
and bapta on the isolated rat heart..
Grandis, Donald J., Pedro J. Delnido, Alan P. Koretsky.
Department of Medicine, Allegheny General Hospital/ Medical College
of Pennsylvania, Pittsburgh PA, 15212, Department of Surgery,
University of Pittsburgh School of Medicine, Pittsburgh PA, 15213,
Department of Biological Sciences, Carnegie-Mellon University, and
Pittsburgh NMR Center for Biomedical Research, Pittsburgh PA,
15213.
APStracts 2:0093C, 1995.
The purpose of this investigation was to study the functional and
energetic effects of the novel positive inotropic agent EMD 57033 and
negative inotropic agent BAPTA [bis-(o-aminophenoxy) -ethane
-N,N,N,N',N'-tetraacetic acid] in the paced, Langendorff-perfused
rat heart. EMD 57033 is a calcium sensitizing agent which has
previously been shown to increase contractility without affecting
calcium transients. Its effects were compared to that of dobutamine
which increases contractility by increasing calcium transient
amplitude. EMD 57033 (2 [mu]mole/l) and dobutamine (0.2 [mu]mole/l) induced
a 40% increase in developed pressure. Myocardial oxygen consumption
(MVO2) increased significantly with dobutamine. However, there was no
significant change in MVO2 with EMD 57033. There was no change in
phosphate metabolite concentrations as detected by 31P NMR with
either agent. Lactate production and basal metabolism were unaffected
by either agent. Thus, EMD 57033 increased contractility in a more
energetically economical manner than did dobutamine. Contractility
was decreased with BAPTA - an intracellular calcium chelator which
decreases contractility by binding free calcium. The metabolic
effects of BAPTA (2.2 [mu]mole/l) were compared to that of verapamil (10
nmole/l), an agent which decreases calcium fluxes. Both agents
decreased developed pressure 60%. MVO2 decreased 14% with BAPTA and
50% with verapamil. Neither agent altered the concentrations of
phosphate metabolites, lactate production or basal metabolism. Thus,
BAPTA lowered contractility in a less energetically economical manner
than verapamil. These data suggest that in rat hearts, inotropic
agents with different effects on calcium handling have different
effects on energetics .
Received 25 February 1994; accepted in final form 23 January
1995.
APS Manuscript Number C100-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.