Daniel Most

Supplemental L-arginine enhances wound healing in diabetic rats

L‐arginine has been shown to enhance wound strength and collagen deposition in rodents and humans. Diabetes mellitus, which impairs wound healing, is accompanied by a reduction in nitric oxide at the wound site. The amino acid L‐arginine is the only substrate for nitric oxide synthesis. We sought to determine whether supplemental L‐arginine can restore the impaired wound healing of diabetic rats. Fifty‐six male Lewis rats were used in this study, of which twenty‐nine rats were rendered diabetic 7u2003days prior to surgery with intraperitoneal streptozotocin. Twenty‐seven untreated rats served as controls. Animals underwent a dorsal skin incision with implantation of polyvinyl‐alcohol sponges. Sixteen diabetic and 14 normal rats received 1u2003g/kg/day of L‐arginine by injection, while the remainder received saline injections only. Animals were euthanized 10u2003days postwounding, and their wounds were analyzed for breaking strength. The wound sponges were assayed for total hydroxyproline and nitrite/nitrate content. Plasma and wound fluid concentrations of L‐arginine, ornithine, and citrulline were determined. Wound sponge RNA was extracted and subjected to Northern blot analysis for procollagen I and III. Diabetic wounds had greatly decreased breaking strengths compared with controls. L‐arginine significantly enhanced wound breaking strengths in both control (+23%) and diabetic animals (+44%), and also increased wound hydroxyproline levels in both diabetic (+40%) and control animals (+24%) as compared to their saline‐treated counterparts. mRNA for procollagen I and III were elevated by L‐arginine treatment in both diabetic rats and controls. Treatment with L‐arginine significantly increased wound fluid nitrite/nitrate levels in diabetic animals. The data show that the impaired healing of diabetic wounds can be partially corrected by L‐arginine supplementation, and that this effect is accompanied by enhanced wound nitric oxide synthesis. (WOUND REP REG 2003;11:198–203)

Role of nitric oxide in wound healing

Nitric oxide is a short-lived free radical, that is capable of multiple effects at the molecular, cellular, and physiologic levels. Over the past several years, nitric oxide has been proved to play an important role in the healing of various types of wounds. The present review examines some of the recently defined roles of nitric oxide in normal and pathologic healing.

Thromboembolism in plastic surgery.

Learning Objectives: After studying this article, the participant should be able to: 1. Appreciate the pathophysiology of deep venous thrombosis and pulmonary embolus. 2. Identify patients at risk for deep venous thrombosis and pulmonary embolus before and after surgery. 3. Recognize modalities for diagnosis and treatment of deep venous thrombosis and pulmonary embolus. 4. Recognize what precautions to take to avoid deep venous thrombosis and pulmonary embolus in plastic surgery patients. Thromboembolism is a dreaded complication of surgery in multiple disciplines, including plastic surgery, and deep venous thrombosis and pulmonary embolus cause significant morbidity, even death. This article provides methods for understanding and preventing deep venous thrombosis and pulmonary embolus in plastic surgery.

Modulation of growth factor and cytokine expression by nitric oxide during rat colon anastomotic healing

We have previously shown that inhibition of nitric oxide generated by inducible nitric oxide synthase (iNOS) results in impaired colon anastomotic healing. Therefore, we proceeded to assess whether disruption of iNOS activity alters the normal pattern of growth factor expression during anastomotic healing. Two groups of male Sprague-Dawley rats underwent distal colonic division and anastomosis, jugular venous catheterization and subcutaneous placement of polyvinyl alcohol sponges. The first group (n = 10) received q8 hour intravenous injections of 10 mg/kg L-N-iminoethyl-lysine (L-NIL, a selective inhibitor of iNOS), while the second group (n = 12) received equal volumes of saline. On postoperative day 5, animals were sacrificed and anastomotic bursting pressure was determined. Histologic sections of the anastomosis were subjected to in situ hybridization versus mRNA of the proteins listed below. Positive controls were reacted with a poly-thymidine (poly-T) probe versus ubiquitous mRNA poly-adenine tails. Positively stained cells were quantified using a calibrated optical grid encompassing 0.5 mm2 area centered over the anastomosis. Results are reported as the number of positive cells per 1000 cells positive for poly-T. L-NIL treated animals demonstrated an 18% decrease in wound fluid NOX compared to controls (29.2 ± 1.2 vs. 34.6 ± 2.0 iM, mean ± SEM; P = 0.035). This corresponded to a 17% decrease in anastomotic bursting pressure (153 ± 4 vs. 182 ± 8 mm Hg, mean ± SEM; P < 0.05). L-NIL also markedly increased the number of cells expressing transforming growth factor-β, tumor necrosis factor-ct, vascular endothelial growth factor, and both inducible and endothelial forms of nitric oxide synthase. L-NIL had no effect on the expression of basic fibroblast growth factor. The data demonstrate that iNOS inhibition markedly disrupts the profile of cytokine and growth factor mRNA normally expressed during anastomotic healing. This provides in vivo evidence that NO modulates gene expression during anastomotic healing.

86 – The Management and Organization of a Surgical Research Laboratory

The successful surgical laboratory is a happy blending of the desire to pursue scientific questions and attention to the many details that have a major impact on the outcome of any research endeavor. The harmonious integration of new members into the lab and their stimulation by a challenging and cooperative environment, as well as a safe workplace, are key elements to a successful laboratory. It is vital that the principal investigator frame formal duties and responsibilities for new lab members. These may range from continuing projects left by others, to starting one or more new projects. If new members are graduate students or postdoctoral fellows with a finite time commitment, it is important to create projects with a reasonable chance of completion within the limited available time. Some lab members will be present only on a part-time basis, thus limiting the duties/projects they may be assigned. Laboratory space for basic science research is an increasingly rare and precious resource. Young investigators joining the faculties of research institutions have often been lured with the promise of lab space as an incentive. Unfortunately, unlimited space is a “pipe dream,” and as one prepares to initiate research, there must be some forethought as to the organization and allocation of space within the lab, especially with regard to present and possible future research projects.