Abstract
Background. This study was designed to determine whether the nitric oxide (NO) pathway is involved
in wound granulation tissue formation. Methods. A section of the pig abdominal wall (excluding the skin) was excised, creating an
incisional hernia. The resulting defect was repaired with silicone sheeting in a manner
that mimics a temporary abdominal wall closure. During the 14-day experimental period,
porcine omentum adhered to the peritoneal edges of the defect and a highly vascularized
granulation tissue formed on both sides of the sheeting. Granulation tissue thickness
and wound fluid volume were monitored by ultrasonography and epigastric artery flow
velocity was monitored by color Doppler flow analysis at days 2, 4, 7, 9, 11, and
14. Fluid was serially harvested from the wound compartment at days 2, 4, 7, 9, 11,
and 14 for nitrite/ nitrate (NOx) analysis. Finally, granulation tissue was harvested
at day 14 for immunohistochemical and molecular analyses. Results. There was a significant increase in granulation tissue thickness and wound fluid
volume during the 14-day study period. Blood flow to the wound increased significantly
by day 4 and returned toward baseline by day 14. Wound fluid NOx levels significantly
increased from days 7 to 11 and then decreased to near baseline values by day 14.
Wound fluid arginine levels significantly decreased when compared with peritoneal
fluid and plasma levels at day 14, while wound fluid ornithine levels significantly
increased. Immunohistochemical analysis of granulation tissue at day 14 revealed nitric
oxide synthase (NOS) 2 was present in the majority of the cells in the granulation
tissue. NOS 3 was expressed in endothelial cells only, and NOS 1 expression was not
observed in the granulation tissue. Conclusions. This study suggests that NO, NOS 2, and arginine may play critical roles in granulation
tissue formation and wound healing. Arginase and NOS 2 may compete for available arginine
as a substrate, thereby limiting later NO production in favor of sustained ornithine
synthesis. (Surgery 2001;129:341-50.)
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Article info
Publication history
Accepted:
September 10,
2000
Footnotes
☆Supported by grants from the American Heart Association; (J. S. P., T. R. H.), the McGhan Medical Corporation, Santa Barbara, Calif (T. R. H.); and a Georgia Institute of Technology/Medical College of Georgia Bioengineering Grant (T. R. H.).
☆☆Reprint requests: Jennifer S. Pollock, PhD, Vascular Biology Center CB3207, Medical College of Georgia, Augusta, GA 30912-2500.
★Surgery 2001;129:341-50.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
