The energetic basis for reduced contractile reserve in isolated rat
hearts.
Tian, Rong, and Joanne S. Ingwall.
NMR Laboratory for Physiological Chemistry, Cardiovascular
Division, Department of Medicine, Brigham and Women's Hospital and
Harvard Medical School, Boston, Massachusetts 02115
APStracts 2:0418H, 1995.
To study the relationship between myocardial energetics and
contractile reserve, we acutely and selectively inhibited creatine
kinase (CK) activity in isolated perfused rat hearts using increasing
doses of iodoacetamide. 31P NMR spectroscopy was used to measure
intracellular pH, [ATP], [PCr] and [Pi]. Contractile reserve was
assessed as the increase of rate pressure product (RPP) from baseline
during high calcium perfusion. Contractile reserve was reduced by 9%,
35% and 72% in hearts with 26%, 6% and 1% CK activity respectively.
An inverse linear relationship between RPP and the free energy
release from ATP hydrolysis ([omega]DGp[omega]) was shown for all
groups. Furthermore, the maximal RPPs of all hearts were achieved at
the same level of [omega]DGp[omega] (52-53 kJ/mol), which is equal to
the free energy requirement of sarcoplasmic reticulum Ca2+ ATPase. We
suggest that inhibition of the CK reaction caused a decrease of
[omega]DGp[omega] which, in turn, limits the Ca2+-handling capacity
of sarcoplasmic reticulum Ca2+ ATPase. In this way, the ability of
the heart to increase its contractile performance is restricted.
Received 22 February 1995; accepted in final form 6 September
1995.
APS Manuscript Number H164-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95