Circulation, Vol 89, 1254-1261, Copyright © 1994 by American Heart Association
V Richard, N Kaeffer, C Tron and C Thuillez
BACKGROUND: Repetitive, brief periods of ischemia and reperfusion
("preconditioning") increase the resistance of myocardial tissue to
subsequent prolonged ischemic episodes and limit infarct size. We
investigated whether preconditioning also protects against coronary
endothelial dysfunction induced by ischemia and reperfusion. METHODS AND
RESULTS: Experiments were performed in four groups of rats (n = 8 in each
group): group 1 rats underwent sham surgery, group 2 rats were subjected to
20 minutes of left coronary artery occlusion without reperfusion, group 3
rats underwent 20 minutes of occlusion followed by 1 hour of reperfusion,
and group 4 rats (preconditioning group) underwent the same protocol as
group 3 rats, preceded by three cycles of 5 minutes of ischemia and 5
minutes of reperfusion. At the end of the experiments, coronary segments
(internal diameter, 250 to 300 microns) were removed distal to the
occlusion site and mounted in wire myographs for isometric tension
recording. Relaxations induced by increasing concentrations of
acetylcholine, the calcium ionophore A23187, or the nitric oxide (NO) donor
SIN-1 were determined in arteries precontracted by serotonin. Basal NO
release was estimated by measuring contractions to NG-nitro L-arginine
methyl ester (L-NAME). In addition, we determined the effect of
preconditioning on infarct size in two additional groups that were
subjected to the same protocols as those of groups 3 and 4. In those
animals, area at risk (India ink injection) and infarct size
(triphenyltetrazolium stain) were determined by computerized analysis of
enlarged sections after video acquisition. Preconditioning markedly limited
infarct size (percent of area at risk: controls, 57 +/- 2; preconditioning,
2.2 +/- 0.6; P < .01). Ischemia (without or with reperfusion) or
preconditioning did not affect the coronary responses to L-NAME, serotonin,
A23187, or SIN-1. Ischemia without reperfusion did not modify the
relaxations to acetylcholine (maximal relaxation: sham, 58 +/- 4%;
ischemia, 56 +/- 7%; P = NS). In contrast, ischemia followed by reperfusion
markedly impaired the response to acetylcholine (26 +/- 6%; P < .01
versus sham). This impaired response was restored by preconditioning
(maximal relaxation: 59 +/- 9%; P = NS versus sham; P < .01 versus
ischemia/reperfusion). CONCLUSIONS: In addition to protecting myocardial
cells, preconditioning also protects coronary endothelial cells against
ischemia/reperfusion injury.
ARTICLES
Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion
Department of Pharmacology, Rouen University School of Medicine, France.
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