Functional effects of emd 57033 in isovolumically-beating isolated
rabbit hearts.
Tobias, Anthony H., Bryan K. Slinker, Robert D. Kirkpatrick, Kenneth
B. Campbell.
Department of Veterinary and Comparative Anatomy, Pharmacology, and
Physiology, Washington State University, Pullman, Washington 99164
-6520
APStracts 2:0525H, 1995.
The results of isolated myocyte and cardiac muscle experiments
indicate that inotropic agents which increase responsiveness of
myofilaments to Ca2+ (so-called Ca2+-sensitizers) may prolong
myocardial contraction and increase diastolic tone, but the
importance of these effects in the whole heart are unclear.
Therefore, we studied the effects of the Ca2+-sensitizer, EMD 57033
(EMD), on left ventricular (LV) contractile events and passive
properties in isovolumically-beating isolated rabbit hearts that were
buffer-perfused at 30 C. Several LV pressure and timing variables
were evaluated, including the passive pressure-volume relationship,
the Frank-Starling relationship, and the wall-stress dependence of
the duration of relaxation, during perfusion with 0, 2, and 4[mu]M
EMD. 2[mu]M EMD increased average peak developed pressure of the
Frank-Starling relationship by 18%. In contrast the peak developed
pressure of the Frank-Starling relationship decreased towards control
with 4[mu]M EMD, and therefore all the results presented pertain to
2[mu]M EMD. The maximum developed pressure at baseline volume was
increased by 19% by 2[mu]M EMD, and this was accompanied by an
increase in contraction duration of 13%, due exclusively to slowed
relaxation. The relative contributions of maximal wall-stress
([sigma]max) versus an independent negative lusitropic effect of EMD
were determined at 3 LV volumes. At baseline volume, just less than
half of the effect to slow relaxation was ascribable to an increase
in [sigma]max, whereas the remainder was due to an independent EMD
effect. LV passive properties were unchanged by perfusion with 2[mu]M
EMD. We conclude that EMD is a potent inotrope in our isolated rabbit
heart preparation, which has no effect on diastolic tone, and causes
a modest prolongation of contraction duration due to slowed
relaxation. At baseline volume, 50% of the slowed relaxation was
ascribable to positive inotropy leading to increased [sigma]max,
whereas the remaining 50% was ascribable to a direct negative
lusitropic effect of EMD. We discuss our results in terms of the
current hypotheses regarding the mechanism of action of the Ca2+
-sensitizers.
Received 22 June 1995; accepted in final form 30 October 1995.
APS Manuscript Number H571-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95