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Circulation, Vol 88, 659-672, Copyright © 1993 by American Heart Association
B Bauer, BZ Simkhovich, RA Kloner and K Przyklenk
BACKGROUND. "Preconditioning" with brief episodes of coronary artery
occlusion reduces infarct size caused by subsequent sustained ischemia.
However, the effects of preconditioning on the coronary vasculature are
poorly understood. We sought to determine whether preconditioning would
attenuate "low reflow" (ie, the deterioration in resting myocardial
perfusion) and blunt the loss in coronary vasodilator reserve after
sustained occlusion/reperfusion in the anesthetized open-chest canine
model. METHODS AND RESULTS. Thirty-two dogs underwent 1 hour of sustained
left anterior descending (LAD) coronary artery occlusion and 4 hours of
reperfusion. Each dog was randomly assigned to the preconditioned group
(four episodes of 5 minutes of LAD occlusion plus 5 minutes of reperfusion
before sustained ischemia) or control group (no intervention). Submaximal
vasodilator reserve was determined by measuring the increase in CBF in
response to 0.01 mg acetylcholine (an endothelium-dependent dilator) and
0.05 mg nitroglycerin (an endothelium-independent dilator); low reflow was
assessed by measurement of regional myocardial blood flow at 30 minutes and
4 hours after reflow; and infarct size was delineated by
triphenyltetrazolium staining. In protocol 1 (n = 14), vasodilator reserve
was measured at baseline and at 30 minutes and 4 hours after reflow. There
was no change in the response to acetylcholine and nitroglycerin at 30
minutes after reperfusion compared with baseline. However, all dogs
exhibited a loss in vasodilator reserve during the subsequent 3.5 hours of
reflow, with no difference between control and preconditioned groups. That
is, in control dogs, acetylcholine increased CBF from a baseline value of
10.1 +/- 1.3 mL/min to 18.0 +/- 2.6, 18.2 +/- 2.1, and 15.4 +/- 1.7 mL/min
before occlusion, 30 minutes after reflow, and 4 hours after reperfusion,
respectively (P < .05 for 30 minutes vs 4 hours after reperfusion).
Similarly, in the preconditioned group, acetylcholine increased CFB from a
baseline value of 12.0 +/- 2.9 mL/min to 19.6 +/- 3.8, 23.6 +/- 5.3, and
15.6 +/- 3.5 mL/min, respectively (P < .01 for 30 minutes vs 4 hours
after reperfusion; P = NS between groups). In addition, all dogs exhibited
low reflow, with no difference between control and preconditioned groups:
subendocardial blood flow deteriorated between 30 minutes and 4 hours after
reflow, from 0.91 +/- 0.20 to 0.40 +/- 0.03 mL min-1 x g-1 in control
animals (P = .05 for 30 minutes vs 4 hours after reperfusion) and from 1.03
+/- 0.25 to 0.35 +/- 0.02 mL.min-1 x g-1 in the preconditioned group (P
< .05 for 30 minutes vs 4 hours after reperfusion). However, all dogs in
protocol 1 had small infarcts (3 +/- 1% and 2 +/- 1% of the risk region in
control and preconditioned groups; P = NS), suggesting that control dogs
may have been "preconditioned" by the vasodilators. An additional 18 dogs
were entered into protocol 2, which was identical to protocol 1 except that
acetylcholine and nitroglycerin were given only after reperfusion. In this
case, we observed the expected reduction in infarct size in preconditioned
dogs vs control dogs (2 +/- 1% vs 11 +/- 3% of the risk region; P <
.01). However, the loss in vasodilator reserve was similar to that observed
in protocol 1, with no difference between groups. Subendocardial blood flow
at 30 minutes after reperfusion was higher in control animals than in
preconditioned dogs (1.84 +/- 0.50 vs 0.74 +/- 0.08 mL.min-1 x g-1; P <
.05), but subendocardial flow then deteriorated during the subsequent 3.5
hours to a similar value in both groups (0.55 +/- 0.11 and 0.50 +/- 0.06
mL.min-1 x g-1 in control and preconditioned dogs; P < .05 vs 30 minutes
after reperfusion for both groups). CONCLUSIONS. The protective effects of
preconditioning do not extend to the coronary vasculature in this canine
model: Preconditioning neither prevented the deterioration in resting
myocardial perfusion nor blunted the loss in submaximal vasodilator reserve
obs
ARTICLES
Does preconditioning protect the coronary vasculature from subsequent ischemia/reperfusion injury?
Heart Institute, Hospital of the Good Samaritan, Los Angeles, CA 90017.
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