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Supplemental l‐arginine enhances wound healing following trauma/hemorrhagic shock

To determine whether parenteral l‐arginine supplementation enhances the impaired wound healing of rats subjected to trauma/hemorrhagic shock. Impaired wound healing after trauma and shock has been documented experimentally and clinically. l‐arginine has been shown to enhance wound strength and collagen synthesis in rodents and humans. Its efficacy under conditions of impaired wound healing is less well defined. Forty‐eight male Lewis rats were used in this study. Using a well‐defined model, 24 rats underwent trauma/hemorrhagic shock before wounding. Twenty‐four untreated rats served as controls. All animals underwent a dorsal skin incision with implantation of polyvinyl‐alcohol sponges. Half of the animals in each group were assigned to receive 1 g/kg/day of l‐arginine by intraperitoneal injection in three divided doses, while the other half received saline injections only. Animals were sacrificed 10 days postwounding, and wound‐breaking strength (WBS) and wound sponge total hydroxyproline (OHP) and nitrite/nitrate (NOx) content were determined. Wound sponge RNA was collected and subjected to Northern blot analysis for procollagens I and III. Trauma/hemorrhage greatly decreased WBS with a concomitant diminution in collagen (OHP) deposition. l‐arginine significantly enhanced WBS (19%) and increased OHP (21%) levels in control animals as well as in rats subjected to trauma/hemorrhage (WBS +29%, OHP 40%) compared with their saline‐treated counterparts. Procollagen I and III mRNA levels were elevated by l‐arginine treatment in both trauma/hemorrhage and control rats. Arginine treatment had no effect on wound fluid and plasma NOx. The data demonstrate that the impaired healing subsequent to trauma/hemorrhage can be greatly alleviated by l‐arginine supplementation.