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Circulation, Vol 74, 1124-1136, Copyright © 1986 by American Heart Association
CE Murry, RB Jennings and KA Reimer
We have previously shown that a brief episode of ischemia slows the rate of
ATP depletion during subsequent ischemic episodes. Additionally,
intermittent reperfusion may be beneficial to the myocardium by washing out
catabolites that have accumulated during ischemia. Thus, we proposed that
multiple brief ischemic episodes might actually protect the heart from a
subsequent sustained ischemic insult. To test this hypothesis, two sets of
experiments were performed. In the first set, one group of dogs (n = 7) was
preconditioned with four 5 min circumflex occlusions, each separated by 5
min of reperfusion, followed by a sustained 40 min occlusion. The control
group (n = 5) received a single 40 min occlusion. In the second study, an
identical preconditioning protocol was followed, and animals (n = 9) then
received a sustained 3 hr occlusion. Control animals (n = 7) received a
single 3 hr occlusion. Animals were allowed 4 days of reperfusion
thereafter. Histologic infarct size then was measured and was related to
the major baseline predictors of infarct size, including the anatomic area
at risk and collateral blood flow. In the 40 min study, preconditioning
with ischemia paradoxically limited infarct size to 25% of that seen in the
control group (p less than .001). Collateral blood flows were not
significantly different in the two groups. In the 3 hr study, there was no
difference between infarct size in the preconditioned and control groups.
The protective effect of preconditioning in the 40 min study may have been
due to reduced ATP depletion and/or to reduced catabolite accumulation
during the sustained occlusion. These results suggest that the multiple
anginal episodes that often precede myocardial infarction in man may delay
cell death after coronary occlusion, and thereby allow for greater salvage
of myocardium through reperfusion therapy.
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