Circulation, Vol 82, 586-594, Copyright © 1990 by American Heart Association
JE Quillen, FW Sellke, LA Brooks and DG Harrison
We examined the effects of ischemia with and without reperfusion on
endothelium-dependent and -independent vascular relaxation in both conduit
and resistance coronary arteries. Studies were performed on dogs under
control conditions (n = 13) or after 1 hour of circumflex coronary artery
occlusion with (n = 10) or without (n = 8) 1 hour of reperfusion. Rings of
obtuse marginal branches of the left circumflex coronary artery (conduit
arteries) were studied in organ chambers. Coronary microvessels
(110-220-microns diameter) were studied in a pressurized state with an in
vitro microvessel imaging apparatus. Relaxation was evaluated after
preconstriction with prostaglandin F2 alpha and U46619 (a thromboxane A2
analogue) in conduit and resistance vessels, respectively. Conduit vessel
function was not altered by ischemia with or without reperfusion.
Endothelium-dependent microvascular relaxation was depressed in response to
acetylcholine, ADP, and calcium ionophore A23187 after ischemia with
reperfusion compared with control relaxation (ED50 as -log[M]: 6.0 +/- 0.2
[p less than 0.05], 5.1 +/- 0.4 [p less than 0.05], and 5.8 +/- 0.1 versus
6.8 +/- 0.2, 6.8 +/- 0.2, and 6.6 +/- 0.2, respectively). Ischemia without
reperfusion modestly altered microvascular endothelium-dependent
relaxation. Microvascular relaxation to nitroglycerin was not altered by
ischemia with reperfusion. We conclude that 1) endothelium-dependent
relaxation in large epicardial coronary arteries is relatively refractory
to ischemia with or without reperfusion, 2) ischemia alone produces mild
alterations of coronary microvascular reactivity, 3) ischemia followed by
reperfusion produces a marked and selective impairment of
endothelium-dependent responses in the coronary microcirculation.
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Ischemia-reperfusion impairs endothelium-dependent relaxation of coronary microvessels but does not affect large arteries
University of Iowa, Cardiovascular Center, Iowa City.
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