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Abstract
Background. Attenuation of endothelium-dependent relaxing factor (EDRF) release may contribute
to adverse sequelae commonly seen after reperfusion of an acutely ischemic extremity.
The purpose of this study was to identify the compound responsible for the EDRF activity
in the extremity and to evaluate its modulation by ischemia and reperfusion.
Methods. Isolated rat hindlimbs were perfused at constant pressure with an albumin-enriched
crystalloid buffer. Increasing log dose infusions of acetylcholine and nitroprusside
were used to measure endothelium-dependent (EDRF-mediated) and endothelium-independent
vasoreactivity, respectively.
Results. Graded reductions in total vascular resistance were seen in response to both agonists
in the control group (n = 11). In the postischemic group (n = 7), 60 minutes of normothermic
ischemia and 10 minutes of reperfusion reduced endothelium-dependent vasodilation
to acetylcholine by approximately 40% (p < 0.01). Endothelium-independent vasodilation
to nitroprusside was unaffected. NG-monomethyl-l-arginine (l-NMMA), a competitive inhibitor of nitric oxide release, attenuated vasodilation to
acetylcholine (p < 0.01) but not nitroprusside in both control and postischemic groups.
Conclusions. Endothelium-dependent vasodilation in the rat hindlimb, mediated by nitric oxide,
was selectively impaired by injury from ischemia and reperfusion. Strategies designed
to minimize postischemic attenuation of nitric oxide release may be beneficial in
the management of acute limb ischemia.
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Article info
Publication history
Accepted:
September 14,
1992
Footnotes
☆Supported by a Department of Veterans Affairs Merit Review Grant and National Institutes of Health grant F32HL08491.
Identification
Copyright
© 1993 Published by Elsevier Inc.
