Abstract
Background
The effects of nitric oxide (NO) on the microcirculation and free tissue survival
remain controversial. With the use of a rat inferior epigastric artery flap as an
ischemia/reperfusion injury (I/R) model, we investigated whether exogenous NO donation
regulates endogenous NO synthase (NOS) expression in the flap vessels and promotes
flap survival.
Methods
Thirty minutes before flap reperfusion, normal saline (1 ml), nitrosoglutathione (GSNO
0.2, 0.6, 3 mg/kg), or NG-nitro-L-arginine-methyl ester (L-NAME, 450 mg/kg), was injected intravenously into
20 rats. Total plasma NOx (NO2-/NO3-) was measured to reflect NO production. Immunohistochemical staining was investigated
for the endothelin-1 (ET-1) and NOS isoforms expression on the flap vessels. NOS isoforms
expression was evaluated by Western blot. Laser-Doppler flowmetry monitored flap perfusion.
Survival areas were assessed by gross examination at 7 days postoperatively.
Results
Flap ischemia at 12 hours followed by reperfusion resulted in endothelial cell damage,
as demonstrated by induction of iNOS and ET-1 expression in the flap vessels. An optimal
dose of nitrosoglutathione (0.6 mg GSNO/kg) significantly increased plasma NOx levels
(P = .027) and improved flap perfusion by laser Doppler measurement (P = .014), and increased the flap viability area (P<.001). Additionally, it selectively suppressed iNOS induction, but enhanced eNOS
expression and decreased ET-1 deposition in the flap vessels. In contrast, an NOS
inhibitor, NG-nitro-L-arginine methyl ester, inhibited both iNOS and eNOS expression in the flap
vessels, decreased endogenous NOx production, and compromised flap viability.
Conclusion
This study indicates that intravenous administration of exogenous GSNO can appropriately
donate NO to suppress iNOS induction and enhance eNOS expression in pedicle vessels,
resulting in better blood perfusion and a higher flap survival after I/R injury.
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Article info
Publication history
Accepted:
July 28,
2003
Kaohsiung, Taiwan, and Örebro, SwedenFootnotes
☆Presented at the 24th Annual Meeting of the American Association of Endocrine Surgeons, San Diego, California, May 11-14, 2003.
☆This work was supported in part by a grant, NSC89-2314-B-182A-06, from the National Science Council; and a grant, CMRP 1097, from Chang Gung Memorial Hospital, Taiwan.
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
