Ischemic Preconditioning Induces Neuroprotection by Activation of Myocardial KATP Channels in Canine Hearts
Date Issued
2003-10-31
Date
2003-10-31
Author(s)
周迺寬
DOI
912314B002230
Abstract
Ischemic preconditioning (IP) reduces
myocardial infarct sizes and decreases the
severity of reperfusion-induced arrhythmias
by activation of different ATP-sensitive K+
(KATP) channels. Recent studies have
demonstrated that the beneficial effect of IP
is not limited to the cardiomyocytes but also
can be observed in cardiac sympathetic
system. Nonexocytotic release of
norepinephrine (NE) during ischemia is a
consequence of increased intracellular
sodium concentrations of the sympathetic
nerve terminal. Excessive release of NE is
deleterious to ischemic myocardium by
inducing intracellular calcium overload and
the degradation of cytoskeletal structure,
3
leading to expansion of the infarct size and
arrhythmia. However, the underlying
mechanism of IP-induced sympatholysis
remains unknown.
Anaesthetized dogs were subjected to 60 min
of the left anterior descending coronary
artery occlusion followed by 3 h of
reperfusion. Infarct size was markedly
reduced in IP-treated dogs compared to
controls (15 ± 6% vs. 43 ± 8%, P < .0001).
Pretreatment with the mitochondrial
ATP-sensitive K+ channel antagonist
5-hydroxydecanoate completely abolished
IP-induced cardioprotection. The
sarcolemmal ATP-sensitive K+ channel
antagonist HMR 1098 did not significantly
attenuate IP-induced infarct size limitation.
Additionally, IP reduced the incidence and
duration of reperfusion-induced ventricular
tachycardia and ventricular fibrillation
significantly. Although 5-hydroxydecanoate
alone caused no significant effect on the
incidence of reperfusion arrhythmias in the
presence or absence of IP, the administration
of HMR 1098 abolished IP-induced
improvement of reperfusion arrhythmias.
IP significantly decreased tissue
norepinephrine of the left ventricle from the
border zone compared with controls. This
reduction in the norepinephrine level was
blocked by either 5-HD and HMR-1098.
These results demonstrate that IP is
cardioprotective against infarct sizes and
fatal reperfusion arrhythmias by different
ATP-sensitive K+ channels for an IP-related
norepinephrine mechanism. The infarct
size-limiting and antiarrhythmic effects of IP
were abolished by 5-hydroxydecanoate and
HMR 1098, suggesting that the effects may
result from activation of the mitochondrial
and sarcolemmal ATP-sensitive K+ channels,
respectively.
Subjects
三磷酸甘敏感鉀離子通道
(ATP-sensitive K+ channels)
(ATP-sensitive K+ channels)
缺血前約制
(IP)
(IP)
神經性保護
正腎上腺素
(Norepinephrine)
(Norepinephrine)
ATP-sensitive potassium channel
Ischemic preconditioning (IP)
Neuroprotection
Norepinephrine
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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