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Cardiac Metabolism Laboratory, Heart Institute, Sheba Medical Center, Tel Hashomer 52621, Israel
We investigated
the hypothesis that a cardioprotective, antiarrhythmic effect might be
obtained by brief ischemia of a remote part of the body before ischemia
of the heart. Regional ischemia (RI) was induced in isolated
Langendorff-perfused rat hearts: group
I, 30-min RI and reperfusion (control hearts;
n = 18); group II, 5-min RI before 30-min RI (a reference group of
"classic" ischemic preconditioning;
n = 12); and group
III, ischemic preconditioning with in vivo 10-min limb
ischemia (LI) before 30-min RI in the perfused heart
(n = 20). A significant decrease in
reperfusion arrhythmia was found in groups
II and III compared
with group I
(P < 0.02). Release of
norepinephrine (NE) and prostacyclin was higher in hearts from animals
pretreated with LI (P < 0.05). Prostacyclin increased in all groups at minute
1 of reperfusion, but there was no correlation to the
antiarrhythmic effect. NE increased at the beginning of reperfusion
after 30 min of ischemia; this release was significantly diminished
after preconditioning with LI (P < 0.05). We further investigated the role of NE in preconditioning with
LI using drug interventions. Pretreatment with exogenous NE protected
against tachyarrhythmia. Reserpine given 24 h before LI partially
abolished the antiarrhythmic effect of LI preconditioning. However, the
1-adrenoreceptor blocker prazosin did not prevent the effect of LI preconditioning on either ischemic or reperfusion tachyarrhythmia. Therefore, brief ischemia of
an extremity protects against reperfusion tachyarrhythmia. One of the
humoral mediators involved in this response appears to be NE; others
remain to be identified.
ischemia at distance; cardioprotection; arrhythmia; humoral mediators; norepinephrine
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