Arginine metabolites in wound fluids from pressure ulcers: a pilot study.

Compelling evidence suggests that nitric oxide (NO*), a metabolite of arginine, plays an important role in wound healing. Arginine is a semi-essential amino acid that is metabolized by nitric oxide synthase and arginase. One model for wound-healing regulation suggests the importance of strict reciprocal control of these enzymes in wounds. The purpose of this pilot study was to investigate arginine metabolism in wound fluids from patients with Stage III or IV pressure ulcers receiving negative pressure wound therapy (NPWT). Wound fluids were collected from 8 patients, aged 31-79 years, before and after initiation of NPWT on Days 1, 3, and 7. Wound fluids were analyzed for nitrates/nitrites (NOx), arginine, citrulline, proline, and ornithine. There were no significant differences between NOx, arginine, citrulline, proline, and ornithine concentrations before and after initiation of NPWT among the various timepoints. However, we observed a downward trend of NO* levels from baseline to Day 7 of NPWT treatment. Furthermore, we detected a decrease in arginine levels over the study period, suggesting that the iNOS/citrulline pathway predominated during the first 72 hr of treatment, and the arginase/ ornithine pathway dominated thereafter. Arginine and its metabolites are detectable in wound fluids from patients with Stage III or IV pressure ulcers on NPWT. Further studies on chronic wounds are warranted to correlate wound-healing outcomes with arginine metabolites at the cellular and molecular level over a longer period of time.

Impact of an absorbent silver-eluting dressing system on lower extremity revascularization wound complications.

Surgical wounds for lower extremity revascularization are prone to infection and dehiscence. Acticoat Absorbent, an antimicrobial dressing, offers sustained release of ionic silver. We hypothesized that immediate application of Acticoat as a postoperative dressing would reduce wound complications in patients undergoing leg revascularization. All infrainguinal revascularization cases involving leg incisions at a single Veterans Administration Medical Center were identified from July 1, 2002, to September 30, 2005. The control group received conventional dressings, while the treatment group received an Acticoat dressing. Wound complication rates were captured via National Surgical Quality Improvement Program data. Patient characteristics and procedure distributions were similar between groups. The wound complication rate fell 64% with utilization of the Acticoat-based dressing (control 14% [17/118], treatment 5% [7/130]; P = 0.016). An Acticoat-based dressing system offers a potentially useful, cost-effective adjunct to reduce open surgical leg revascularization wound complications.

Arginine supplementation and wound healing.

Modern advances in nutritional therapies have led to the specific use of arginine supplementation for protein synthesis, cell signaling through the production of nitric oxide, and cell proliferation through its metabolism to ornithine and to polyamines. Arginine is classified as a nonessential amino acid that becomes a conditionally essential substrate in stressed adults. Arginine has been shown to enhance wound strength and collagen deposition in artificial incisional wounds in rodents and humans. A role for dietary intervention in the form of arginine supplementation has been proposed to normalize or enhance wound healing in humans. Although this hypothesis is frequently discussed, the therapeutic effect of arginine supplementation on chronic wound healing in humans is still undetermined and requires further objective evidence. Well-designed clinical trials are required to determine whether arginine supplementation is effective in enhancing healing of acute and chronic wounds in humans and how much arginine is recommended to meet metabolic needs during the phases of wound healing.

Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers.

The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.

Arginine immunonutrition in critically ill patients: a clinical dilemma.

Commercial enteral nutritional formulas for enhancement of the immune system are widely used in critical care. Immunonutrition with arginine can enhance inflammatory and immunologic responses in animal models and in humans. Although clinical improvements in surgical patients have been reported, benefits in critically ill patients with systemic inflammatory response syndrome, sepsis, or organ failure are less clear. Recent meta-analyses on the use of immunonutrition with arginine in critically ill and surgical patients revealed methodological weaknesses in most published studies. Specifically, a meta-analysis indicated that critically ill patients with preexisting severe sepsis may have an increased mortality rate when fed an immunonutritional enteral formula that contains arginine. These findings brought about confusion and controversy over the use of immunonutritional formulas in subsets of critically ill patients. A review of the literature on the function of arginine, its effect on the immune system, its roles in immunonutrition and in the clinical outcomes of critically ill patients, and the implications for nursing practice indicated that the benefits of immunonutrition with arginine in critically ill patients are unproven and warrant further study. Until more information is available, nutritional support should focus primarily on preventing nutritional deficiencies rather than on immunomodulation.

Role of nitric oxide in wound healing.

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and sufferfrom a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatoryforces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.