Remote postconditioning
Tóm tắt
A series of brief coronary artery reperfusions and reocclusions
applied during the early minutes of coronary artery reflow (“postconditioning”)
attenuates reperfusion injury. However, it is not known
whether brief ischemia–reperfusion applied to a distant organ at the onset of
myocardial reperfusion (i.e. “remote postconditioning”, remote PostC)
reduces infarct size in the reperfused myocardium. In an in vivo anesthetized
rat model of myocardial infarction induced by coronary artery occlusion and
reperfusion, this study tested the hypothesis that remote postC induced by a
single 5 minute episode of renal artery (RA) occlusion and reperfusion
applied immediately before the onset of coronary artery reperfusion protects
the myocardium from reperfusion injury by mechanisms involving endogenous
adenosine receptor activation. All rats were subjected to a
total of 30 minutes of left coronary artery occlusion (LCAO) and 3 hours of
reperfusion. The rats were randomized to one of six groups: 1) Control: LCAO
and reperfusion only with no other intervention; 2) Remote PostC: after 24
minutes of LCAO the RA was occluded for 5 minutes and released 1 min
before coronary artery reperfusion; 3) Permanent RA occlusion: the RA was
permanently occluded after 24 minutes LCAO continuing to the end of
reperfusion; 4) Delayed Remote PostC: after 26 minutes LCAO the RA was
occluded for 5 minutes, and its release was delayed until 1 min after coronary
artery reperfusion; 5) CON + SPT: rats with LCAO and reperfusion received
10 mg/kg IV of the non–selective adenosine receptor antagonist 8–sulfophenyl
theophylline [SPT] administered 5 minutes before coronary artery reperfusion;
and 6) Remote PostC + SPT: after 24 minutes of LCAO the RA was
occluded for 5 minutes and released 1 minute before coronary artery reperfusion
in the presence of 10 mg/kg SPT given 5 min before coronary artery
reperfusion. Myocardial infarct size (percentage necrosis/area at
risk, mean ± SEM) was reduced by 50% in Remote PostC (25 ± 4%) compared
to Control (49 ± 4%, p = 0.003), consistent with a reduction in plasma CK
activity (44 ± 5 vs. 67 ± 6 U/ml, p = 0.023). In contrast, permanent RA occlusion
before LCAO and reperfusion failed to reduce myocardial infarct size (47
± 5%) vs Control. Delaying the release of the RA occlusion (delayed Remote
PostC) abrogated the myocardial infarct reduction observed with Remote
PostC (48 ± 6%). SPT alone had no effect on infarct size (47 ± 4% in CON +
SPT vs. 49 ± 4% in CON); however, Remote PostC+SPT abrogated the
myocardial infarct size reduction in Remote PostC (50 ± 3% in Remote
PostC + SPT vs. 25 ± 4% in Remote PostC). Remote renal postconditioning
applied immediately before the onset of coronary artery reperfusion
provides potent myocardial infarct size reduction likely exerted during the first minutes of coronary artery reperfusion. This inter–organ remote
postconditioning phenomenon is likely mediated in part by release of
adenosine by the ischemic–reperfused kidney and subsequent activation of
adenosine receptors.
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