Experimental studies on the effect of lidocaine on wound healing

Local anesthetics have several effects on wound healing. In experimental studies, procaine at high concentrations has been proved to retard healing in surgical wounds by diminishing the synthesis of mucopolysaccharides and hence probably collagen. Other studies have shown that lidocaine and bupivacaine inhibit collagen synthesis in fibroblast tissue cultures in rats. This study was designed to evaluate the effect of lidocaine on wound healing. An experimental, prospective, comparative, crossover and double-blind study was designed. Forty male guinea pigs, weighing 300 to 600 g, were randomly assigned to two groups. In control group A (20 animals), skin and subcutaneous tissue in a clean wound were incised and infiltrated with regular saline solution; in group B 20 animals were infiltrated with 1% lidocaine. All animals were sacrificed on day 8 and evaluated for breaking strength, number of collagen fibers by morphometry, and histologic examination of collagenization, edema, vascularity, and presence of acute and chronic inflammatory cells. The histopathologic appearance of tissues infiltrated with lidocaine did not vary consistently in relation to collagenization, edema, or acute and chronic inflammatory processes. The mean breaking strength between both groups was not statistically significant (p = 0.120). Important statistical differences were observed in vascularity (p < 0.003) and morphometric results (p < 0.001), where collagen was found in small amounts in the lidocaine group. The results of this study suggest that local infiltration of lidocaine produces significant histopathologic changes, but it does not substantially alter wound healing as there were no differences in the breaking strength of the wounds.     

Histological research on the effect of viruses on wound healing

The influence of pure virus solution on wound healing was studied in animals. The rate of disturbed wound healing was proportional to the concentration of the virus solution. Severe necrosis without inflammatory reaction could be demonstrated histologically.     

The effect of different way of using FGF on wound healing

The UVU1 CHO cell line, a double mutant of the excision repair complementation group 1 UV4 cell line was characterized by a higher UV sensitivity than its parent (Busch et al (1989) Mutagenesis 4, 349-354). We show here that this mutant is not affected in a UV mutagenic pathway. In addition, the UVU1 cell line is about two-fold more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine treatment than its parent without being more sensitive to cross-linking agents or ionizing radiations.     

Nutrition and wound healing

This paper reviews evidence that suggests malnutrition exists among the sick population in hospital and at home, a situation that has not improved in 20 years. It examines the consequences of malnutrition in broad terms and its effect on wound healing. The role of specific nutrients for wound healing is discussed, and finally the barriers which prevent nurses from delivering adequate patient nutrition are exposed.     

The effect of prednisolone on the systemic response and wound healing after colonic surgery

To study the effect of preoperative treatment with a single high-dose of glucocorticoid on the systemic and immunological response, wound healing, and convalescence after colonic surgery, thirty patients were double-blind randomized to receive either methylprednisolone 30 mg/kg intravenously 90 minutes prior to induction of anaesthesia (group 1, n = 12), or to receive placebo (group 2, n = 12). Six patients were excluded from the study. Assessments of pain, pulmonary function, convalescence, various injury and wound-healing factors were done until 10 days after surgery. Conventional reduction in pulmonary function and mobilization was improved in group 1. Interleukin-6 and C-reactive protein levels increased significantly less in group 1, as delayed-type hypersensitivity was abolished in group 1. Plasma cascade system activation was significantly less pronounced in group 1. Reduction of collagen turnover was observed in group 1, but without detrimental effect on collagen accumulation. It is concluded that treatment with a single high dose of glucocorticoid before colonic surgery may improve postoperative pulmonary function and mobilization and reduce plasma cascade system activations, the inflammatory response, and immunofunction, but without detrimental effects on wound healing.     

Effect of norepinephrine on gastric wound healing

Lavage of the stomach with norepinephrine has been suggested as a temporary means of controlling upper gastrointestinal tract bleeding. The effect of norepinephrine on the healing of a standard gastric incision in the rat was studied using irrigation topically. When compared with those rats in the control study that were irrigated with a saline solution alone, no significant difference was found in the tensile strength, local inflammatory response or synthesis of new collagen, as determined by the hydroxyproline-proline ratio. There would appear to be no adverse effect on gastric wound healing as a result of preliminary irrigation of the gastric mucosa with norepinephrine given topically in a concentration of 16 milligrams per liter.     

General principles of wound healing

Wound healing is a complex process involving different biologic and immunologic systems. Despite improvements in diagnostics and therapy, wound failures remain a clinical problem. The approach to a nonhealed wound is an interdisciplinary challenge that should not be underestimated. Better understanding of the complex wound-healing cascade helps our approach to wound healing and its possible failure. Manipulations of the involved immunologic features offer future therapeutic strategies.     

Nutritional aspects of wound healing

The nutritional aspects of wound healing include completing a nutritional assessment, estimating a patient's nutrient needs, and evaluating options for medical nutrition therapy. Some key nutrients involved in wound healing are discussed and their food sources described.     

Fetal tissue repair and wound healing

The fibrosis and scar formation that characterize adult wound healing are also the cause of clinical problems; scar contracture, hypertrophic scar, and pulmonary and hepatic fibrosis are only a few examples. Studies of fetal wound healing can provide an insight into the initiation and regulation of a scarless repair process akin to regeneration. Studies of fetal repair have already suggested mechanisms that might favorably alter adult healing. Topical application of hyaluronic acid to wounds in adult diabetic rats leads to enhanced epithelial migration. It has been recognized that the addition of TGF-beta to fetal wounds causes an adultlike healing response with fibrosis and inflammation. A subsequent study using neutralizing antibody to TGF-beta in adult wounds showed enhanced healing with a more normal dermal architecture with fewer macrophages, fewer blood vessels, and less collagen. As our understanding of regenerative tissue repair increases, the opportunities to modulate adult fibrotic conditions should expand.     

The effect of octreotide on wound healing: an in vitro and in vivo experimental study

OBJECTIVE: To investigate the effect of octreotide on wound healing. DESIGN: Experimental studies in vitro and in rats. SETTING: Teaching hospital, Israel. MATERIAL: Cultured human diploid fetal fibroblasts, and 36 male Wistar rats. INTERVENTIONS: Octreotide was added to cultures of fibroblasts in doses of 2, 10, 30, 60 and 120 ng/ml and fibroblasts were counted after 2, 4, and 6 days. Intestinal anastomoses were made in 36 rats. Rats in the octreotide group (n = 18) were given subcutaneous injections of 0.25 microg/kg twice daily and 6 rats were killed at 3, 7, and 14 days. The control group were given injections of saline. Anastomotic bursting pressures and hydroxyproline content were measured at each of the three times. MAIN OUTCOME MEASURES: Fibroblast counts, anastomotic bursting pressures, and hydroxyproline concentrations. RESULTS: Octreotide did not inhibit fibroblast proliferation in any of the doses at any of the time periods. The anastomotic bursting pressure was slightly higher in the octreotide group at each of the time points, but not significantly so, and there was no difference in hydroxyproline content between the octreotide and control groups. Octreotide did not inhibit wound healing either in vitro or in vivo.     

Ultrastructural study of the skin after facial chemical peels and the effect of moisturization on wound healing

Ultrastructural changes occurring in the skin at early times after chemical peels as well as effects on the wound healing with moisturization after these peels have been examined. This study evaluated the changes seen in the skin 3 days and 5 days after 35% trichloroacetic acid peels, and the effect of moisturization on this healing was evaluated. Biopsies at 3 days showed an outermost layer of necrotic stratum corneum and stratum granulosum and an underlying layer of new stratum corneum. There were increased cytoplasmic vacuoles in the keratinocytes of the stratum spinosum, stratum granulosum, and stratum basale layers. There was extensive intercellular spacing between the basal keratinocytes. At 5 days the necrotic layer of stratum corneum and stratum granulosum was gone. The lower epidermis at 5 days showed less intercellular spacing, and there was less vacuolization within keratinocytes. In seven of eight patients treated with moisturization after the peel (p = 0.0325), the ultrastructural changes at 5 days were consistent with a more advanced state of healing compared with those that were treated dry. Ultrastructural morphology at this time showed less intercellular spacing and fewer cytoplasmic vacuoles, indicative of an advanced state of wound repair. These moisturized skin specimens had returned to an almost normal state of structure compared with the skin that had been treated dry.     

Influence of methylprednisolone and transforming growth factor-beta on wound healing

This study was aimed at evaluating the influence of transforming growth factor-beta (TGF-beta) on methylprednisolone induced inhibition of wound healing. C57BL/6 mice underwent a standardized dorsal incision. At regular intervals after wounding the mice were sacrificed and their pelts were excised. The fresh breaking strength (FBS) of the pelts was then measured with a constant-speed tension meter. 1) In the first experiment, designed to determine if methylprednisolone did in fact have any inhibiting effect on wound healing, mice received methylprednisolone and a control group received saline. Both methylprednisolone and saline were administered for a four day period. In this experiment the FBS of methylprednisolone treated mice was weaker than that of the control group on the 14th and the 21st day. 2) In the second experiment, designed to determine when the administration of methylprednisolone most noticeably inhibited wound healing, mice were divided into three groups which received methylprednisolone in the following manner: for three days prior to wounding, on the day of wounding, and for three days immediately following wounding. The fourth group received no methylprednisolone at all. The FBS of mice treated with methylprednisolone for three days prior to wounding was weaker than that of the control group on the 14th day after wounding, but showed no significant difference on the 21st day after wounding. The FBS of mice treated on the operative day was weaker on both the 14th and the 21st day after wounding. The FBS of mice treated three days after wounding showed no significant difference on the 14th day after wounding, but was weaker than the control group on the 21st day after wounding. 3) In the third experiment, designed to determine at what time the administration of TGF-beta most accelerated wound healing, mice were divided into three groups which received TGF-beta at different intervals. The first group received TGF-beta on the day of wounding, the second group received TGF-beta on the third day after wounding, and the third group received TGF-beta on the 7th day after wounding. A control group received no treatment. In this experiment the FBS of mice treated with TGF-beta on the third day after wounding was stronger than that of the control group when measured on the 7th and 11th day after wounding, but there was no significant difference on the 14th day. The FBS of mice treated on the day of wounding and mice treated on the 7th day after wounding was not significantly different from that of the control group. 4) In the fourth experiment, designed to determine if TGF-beta can prevent methylprednisolone-induced inhibition of wound healing, mice were divided into three groups. The first group received methylprednisolone for four days prior to wounding. On the third day after wounding they were given saline. The second group also received methylprednisolone for four days prior to wounding, but was treated with TGF-beta on the third day after wounding. The third group received no methylprednisolone, and was given saline three days after wounding. In this experiment the FBS of mice which received only methylprednisolone and saline was weaker than that of the control group on both the 14th and the 21st day after wounding. However, there was no significant difference between the FBS of methylprednisolone treated mice which received TGF-beta and the control group on both the 14th and the 21st day after wounding. From these results the following conclusions were drawn: 1) Methylprednisolone does inhibit wound healing. 2) The influence of methylprednisolone on wound healing is stronger if it is received on operative day. 3) TGF-beta can accelerate wound healing. 4) TGF-beta can prevent methylprednisolone induced inhibition of wound healing.     

Angiogenesis in wound healing and tumor metastasis

Formation of new blood vessels is essential for several physiological and pathological events, e.g. embryogenesis, wound healing and tumor growth and metastasis. In order to increase the insight into the mechanisms of angiogenesis we have visualized the different components of the microvasculature in human wounds and tumors by immunohistochemistry on the light and electronmicroscopic level. For this purpose, antibodies recognizing distinct markers for human endothelial cells, pericytes and basal lamina were used on freshly frozen or paraformaldehyde-fixed tissue samples. In terms of efficacy, the PAL-E antigen is highly specific for blood vessel endothelium. Its sensitivity is less than other endothelial markers, such as von Willebrand factor and CD 31, as it is not expressed in arterioles. Within the context of the microvasculature alpha-smooth muscle actin and the HMW-MAA chondroitin sulphate proteoglycan are useful markers for pericytes. Type IV Collagen and Laminin can be visualized consistently in the microvascular basal lamina. During the formation of granulation tissue in wound healing a heterogeneity of the expression of endothelial and pericyte markers is found. In the least matured zone in granulation tissue of decubitus lesions and experimental skin wounds microvessels already contained both endothelial cells and pericytes, suggesting a role for both cell types in the early steps of angiogenesis. Regarding the tumor microvasculature, antibodies to von Willebrand factor often failed to stain capillaries, that did show expression of the other endothelial markers studied. Broad staining in pericytes was found for the HMW-MAA chondroitin sulphate proteoglycan. In contrast, these cells only locally expressed alpha-smooth muscle actin. Staining of the basal lamina components Type IV Collagen and Laminin within tumors was not restricted to the microvasculature. Therefore, antibodies recognizing endothelial markers, particularly PAL-E and BMA 120, are preferable as tools to visualize the tumor microvasculature. In accordance with the situation in granulation tissue of wound healing the broad presence of pericytes in the microvasculature of human tumor suggests an involvement of this cell type in tumor angiogenesis. Recent immunohistochemical studies on human tumor lesions indicated that a high number of microvessels adjacent to the tumor as a measure of tumor angiogenesis is an unfavorable prognostic factor in cutaneous melanoma, mammary carcinoma and non-small cell pulmonary carcinoma. This new application of immunohistochemistry represents a valuable, clinically relevant adjunct to the repertoire of the surgical pathologist.     

Metalloproteinase inhibitors and wound healing: a novel enhancer of wound strength

BACKGROUND: Wound strength is a balance between collagen synthesis and degradation. The role of collagen breakdown in wound healing is still not well understood. We investigated the role of collagenases (metalloproteinases [MMPs]) in wound healing in using GM6001, a novel inhibitor of MMPs. METHODS: We used the dorsal skin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (10 mg/kg body weight) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxyproline content, and collagen type I gene expression in sponges were assayed. In addition, the inflammatory response and the wound fluid cytokine (tumor necrosis factor-alpha [TNF-alpha] and transforming growth factor-beta 1 [TGF-beta 1]) profile were studied. RESULTS: GM6001 significantly increased wound strength (422 +/- 59 vs 302 +/- 33 g, P < .05), whereas scar collagen content did not differ. In the sponge granulomas the inflammatory infiltrate, the collagen content, and the collagen type I gene expression were all significantly decreased by GM6001. CONCLUSIONS: Inhibition of MMP activity during acute wound healing enhances wound strength even though new collagen synthesis and the inflammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking, or both.