L-arginine improves wound healing after trauma-hemorrhage by increasing collagen synthesis.
BACKGROUND
Several studies indicate impaired wound healing after trauma and shock. Wound immune cell dysfunction seems to be responsible for altered wound healing after trauma-hemorrhage (T-H). In this respect, administration of the amino acid L-arginine normalized wound immune cell function under those conditions. It remains unknown, however, whether L-arginine improves impaired wound healing after T-H.


METHODS
To study this, male C3H/HeN mice were subjected to a midline laparotomy (i.e., soft tissue trauma induced), and polyvinyl sponges were implanted subcutaneously at the wound site before hemorrhage (35 +/- 5 mm Hg for 90 minutes) or were subjected to sham operation. During resuscitation, mice received 300 mg/kg body weight L-arginine or saline (vehicle). Seven days thereafter, hydroxyproline (OHP), a metabolite of collagen synthesis, was measured in the wound fluid using high-performance liquid chromatography. Collagen types I and III were determined in the wound by Western blot analysis. In addition, wound breaking strength was measured 10 days after T-H or sham operation.


RESULTS
The results indicate that OHP was significantly decreased in T-H mice. L-arginine, however, restored depressed OHP in the wound fluid in the T-H animals. Similarly, L-arginine treatment prevented a significant depression of collagen I synthesis after T-H. Collagen III was not significantly affected by T-H or L-arginine. Most important, L-arginine increased maximal wound breaking strength after severe blood loss. Therefore, L-arginine improves wound healing after T-H by increasing collagen synthesis.


CONCLUSIONS
Because L-arginine improves wound healing, the results suggest that L-arginine might represent a novel and useful adjunct to fluid resuscitation for decreasing wound complications after trauma and severe blood loss.
Wittmann
F
F
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Prix
N
N
Mayr
S
S
Angele
P
P
Wichmann
M W
MW
van den Engel
N K
NK
Hernandez-Richter
T
T
Chaudry
I H
IH
Jauch
K W
KW
Angele
Martin K
MK
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism*; D006470:Hemorrhage / Q000503:physiopathology*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011897:Random Allocation; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000276:immunology
D016212:Transforming Growth Factor beta; D003094:Collagen; D001120:Arginine; D006909:Hydroxyproline