Enhanced sarcoplasmic reticulum function in saponin-treated left
and right ventricular trabeculae from rabbits with heart failure.
Denvir, Ma, Ng Macfarlane, Dj Miller, Sm Cobbe.
Department of Medical Cardiology, Glasgow Royal Infirmary and
Institute of Biomedical and Life Sciences*, University of Glasgow,
Scotland, UK
APStracts 3:0065H, 1996.
Cardiac sarcoplasmic reticulum calcium loading ability was assessed in
a coronary artery ligation model of heart failure. Heart failure was
produced in New Zealand White rabbits by ligation of the left
marginal coronary artery. Sham-operated animals were used as
controls. Following haemodynamic and echocardiographic assessment 8
weeks after coronary ligation, a free running trabecula was isolated
from the left or right ventricle, mounted for isometric tension
measurement and permeabilised with the chemical skinning agent
saponin, leaving the sarcoplasmic reticulum (SR) functionally intact.
The SR was Ca2+-loaded by exposure of the preparation to a mock
intracellular solution containing 150-300nM [Ca2+]. The amplitude of
the caffeine-induced contracture was used as a measure of the calcium
loaded by the SR. The same preparation was then treated with Triton-X
100, to disrupt all cell membranes, and measurements of calcium
sensitivity of isometric tension production and maximum calcium
activated force (Cmax) were made. Ligated animals demonstrated
enhanced SR Ca2+-loading ability which correlated with the degree of
left ventricular dysfunction. Enhanced SR Ca2+-loading was associated
with evidence of SR Ca2+-overload revealed as spontaneous tension
oscillations. Cmax and calcium sensitivity (pCa50) were not
significantly different from controls. Increased SR Ca2+-loading
ability may predispose the SR to calcium overload and could
contribute to both contractile dysfunction and arrhythmogenesis in
heart failure.
Received 23 May 1995; accepted in final form 17 January 1996.
APS Manuscript Number H482-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96