Preconditioning prevents chronic reperfusion - induced coronary
endothelial dysfunction in rats.
Kaeffer, Nathalie, Vincent Richard, Arnaud Fran[cedilla]cois,
Francoise Lallemand, Jean-Paul Henry, and Christian Thuillez.
Department of Pharmacology, (Groupe vaisseaux - c_ur -
m[acute]edicaments, Institut F[acute]ed[acute]eratif de Recherches n
degrees 23 - "peptides") and Pathology, Rouen University
Medical School and Rouen University Hospital, 76031 Rouen, France
APStracts 3:0115H, 1996.
Experiments were designed to test whether preconditioning protects
against chronic endothelial injury after ischemia and reperfusion.
Coronary arteries were isolated from rats subjected to sham surgery
or 20 min ischemia followed by 1 hour, 1 day, 1 week or 1 month
reperfusion, without or with preconditioning. The endothelium
-dependent relaxations to acetylcholine (assessed in vitro) were
markedly reduced after ischemia and 1 hour reperfusion (31+/-6 vs
57+/-6% in sham; p<0.01), and did not recover after longer
durations of reperfusion (1 month: 32+/-5% vs 56+/-2; p<0.01).
The impaired response to acetylcholine was restored by
preconditioning at all time points (1 hour: 53+/-6; 1 month: 65+/
-4%). After 1 month, the potency of acetylcholine in preconditioned
arteries was also increased as compared to sham animals. Electron
microscopy showed marked endothelial damage after 1 hour of
reperfusion, and signs of regenerated endothelium after 1 month of
reperfusion. Both acute and chronic ultrastructural changes were
prevented by preconditioning. Thus, preconditioning, in addition to
protecting myocardial cells, also protects against chronic
reperfusion - induced endothelial injury, both in terms of functional
and structural changes.
Received 27 July 1995; accepted in final form 14 February 1996.
APS Manuscript Number H708-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96