Thromboembolism in plastic surgery.

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.

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 7 days 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 1 g/kg/day of L-arginine by injection, while the remainder received saline injections only. Animals were euthanized 10 days 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.

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 mm(2) 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 NO(X) compared to controls (29.2 +/- 1.2 vs. 34.6 +/- 2.0 microM, 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-beta, tumor necrosis factor-alpha, 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.

Characterization of incisional wound healing in inducible nitric oxide synthase knockout mice.

BACKGROUND: Excisional wound healing in inducible nitric oxide synthase knockout (iNOS-KO) mice has been previously shown to be impaired compared with their background strain controls. Incisional wounds were created in this experiment in both types of animals and paradoxically were found to heal with the same rapidity and breaking strength in both groups. METHODS: Dorsal 2.5 cm incisional wounds were created in iNOS-KO mice, as well as their parental strain controls (C57BL/6J). Standardized polyvinyl alcohol sponges were implanted in the wounds to allow for measurement of collagen deposition. Animals were harvested on postoperative days (PODs) 3, 5, 7, 10, 14, and 28, and their wounds subjected to tensiometric breaking strength analysis. Nonisotopic in situ hybridization quantitative analysis for iNOS, endothelial NOS (eNOS), basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), and interleukin-4 (IL-4) expression in the wounds was performed. Hydroxyproline levels were quantitated in the harvested polyvinyl alcohol sponges. Data were analyzed with the Students t test. RESULTS: No significant differences were found in breaking strengths or levels of hydroxyproline (and thus collagen) in iNOS-KO versus wild-type wounds at all tested time points. Flawed iNOS expression levels in iNOS-KO animals were similar to (functional) iNOS expression in wild-types. eNOS and bFGF expression nearly doubled on POD 7 in iNOS-KO incisions (P =.002, and.002), respectively and remained 200% to 300% elevated thereafter. TGF-beta1 expression was increased approximately 50% to 100% in iNOS-KO wounds on PODs 5 and 7 (P =.006 and.01, respectively). VEGF and IL-4 expression was elevated by 25% to 100% in wild-type compared with iNOS-KO animals at all time points (P <.01). CONCLUSIONS: The overexpression of TGF-beta1 and eNOS may represent mechanisms in iNOS-KO mice to compensate for their loss of functional iNOS, resulting in incisional wound healing equivalent to controls. Their impaired expression of VEGF and IL-4, on the other hand, may partially explain the delayed excisional wound healing noted in these animals.

A Method for Immobilizing the Forelimbs of Rabbits.

Immobilizing the forelimbs of rabbits after surgical procedures is necessary to allow healing, yet it often can be difficult, because rabbits are often able to pull the repaired limb from its cast soon after surgery and well before adequate tissue repair has taken place. We describe here a method of immobilization that uses 3 layers of cast material combined with flexion of the radiocarpal and radiohumeral joints. This method resulted in successful immobilization in 97% of the rabbits on which it was used.