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From the Departments of Clinical and Experimental Cardiology (L.R.C.D.,
H.R., J.T.V., T.O., R.C., M.J.J.) and Medical Physics (J.A.E.S.), Academic
Medical Center, Amsterdam, Netherlands.
Correspondence to Dr L.R.C. Dekker, Academic Medical Center, M-0–54, Department of Experimental Cardiology, PO Box 22700, 1100 DE Amsterdam, Netherlands. E-mail LRDekker{at}AMC.UVA.NL
Background—Patients with heart
failure show a very high incidence of arrhythmias and sudden
death that is often preceded by ischemia; however, data on
electrophysiological changes during
ischemia in failing myocardium are sparse. We
studied electrical uncoupling during ischemia in normal and
failing myocardium.
Methods and Results—Tissue resistance, intracellular
Ca2+ concentration (Indo-1 fluorescence ratio), and
mechanical activity were simultaneously determined in
arterially perfused right ventricular papillary
muscles from 11 normal and 15 failing rabbits. Heart failure was
induced by combined volume and pressure overload. Before sustained
ischemia, muscles were subjected to control perfusion (non-PC)
or ischemic preconditioning (PC). The onset of uncoupling
during ischemia was equal in non-PC normal (13.6±0.9 minutes
of ischemia) and non-PC failing hearts (13.3±0.7 minutes of
ischemia). PC postponed uncoupling in normal hearts by 10
minutes. In failing hearts, however, PC caused a large variability in
the onset of uncoupling during ischemia (mean, 12.2.±2.1;
range, 5 to 22 minutes of ischemia). The duration of uncoupling
process was prolonged in failing hearts (12.9±0.9 minutes) compared
with normal hearts (7.8±0.4 minutes). The degree of heart failure and
relative heart weight of the failing hearts significantly correlated
with the earlier uncoupling after PC and the duration of uncoupling. In
every experiment, the start of Ca2+ rise and contracture
preceded uncoupling during ischemia.
Conclusions—The duration of the process of
ischemia-induced electrical uncoupling in failing hearts is
prolonged compared with that in normal hearts. Ischemic PC has
detrimental effects in severely failing papillary muscles because it
advances the moment of irreversible ischemic damage.
© 1998 American Heart Association, Inc.
Basic Science Reports
Cellular Uncoupling During Ischemia in Hypertrophied and Failing Rabbit Ventricular Myocardium
Effects of Preconditioning
Key Words: heart failure • ischemia • arrhythmia • calcium
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