[Modification of wound healing and wound pain by direct intravenous oxygen insufflation. A contribution to the effect of the method by H. S. Regelsberger].
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Recent investigations of HELPAP and CREMER 1972 seem to confirm the supposition of COHNHEIM 1867 that monocytes of the peripheral blood are transformed into firbroblasts in healing wounds. The view of VIRCHOW 1871, MARCHAND 1901 and ASCHOFF 1924 that the fibroblasts in healing wounds are of local origin seems to be supported by the invesigation on parabiotic inbred rats of ROSS et al. 1970. We thought that irradiating the whole body of rabbits could be of value in resolving these apparent contradictions about the origin of fibroblasts in healing wounds.
The effect on the tensile strength of healing wounds of 2 of the most commonly used antifibrinolytic substances, tranexamic acid and epsilon-aminocaproic acid, has been studied in white rats. 2 symmetrical linear lines were made on the dorsal skin, in 1 of which was injected 1 ml of the test solution. The incisions were closed with interrupted sutures, and after 7 days the animal was sacrificed, the wound excised and its tensile strength determined. The results showed tranexamic acid (1 ml of a solution containing 100 mg/ml) to have a positive effect on wound healing, whereas epsilon-aminocaproic acid (1 ml of a solution containing 400 mg/ml) had a negative effect. When both agents were compared in the same animal, wounds in tissue injected with tranexamic acid had a higher tensile strength than those made in tissue pre-treated with epsilon-aminocaproic acid. Even compared at the same ionic strength, similar results were obtained. It is clear from this investigation that, unlike epsilon-aminocaproic acid, tranexamic acid has a positive effect on wound healing, and that this effect is not due to the antifibrinolytic properties, as both are powerful fibrinolytic inhibitors.
Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.
The advancing technologies available to the orthopedist are a necessary adjunct to heal wounds about the foot and ankle successfully. Successful wound healing should be viewed as a multidisciplinary approach, using the strengths of each discipline. Critical to an integrated method is communication preoperatively between the orthopedist and the plastic surgeon to create a streamlined process. This leads not only to improved rates of wound healing, but also to improved functional outcomes while reducing risks for recurrence.
When a tissue graft is introduced into a healing wound, the inflammatory and proliferative stages of wound healing are significantly prolonged. This sustained stimulation at the surrounding graft site can develop into chronic inflammation, leading to fibrosis and connective tissue build-up around the graft. Persistence in chronic inflammation surrounding a tissue graft can lead to graft destruction or rejection. Thus, a basic understanding of soft-tissue wound healing in response to grafted tissue is important to optimize the long-term functional results of tissue grafts.
PURPOSE: The extracellular matrix that is present at sites of tissue repair in most instances undergoes an orderly transition from a fibrin containing matrix to collagen-rich scar. However, in some conditions, such as Peyronie's disease, fibrin persists. Evidence from a number of experimental systems indicates that extracellular matrix proteins and their receptors serve an important function in regulating cell behaviors. Thus, the presence of the fibrin matrix is likely to have important implications in the course of either normal or pathogenic wound healing as occurs in Peyronie's disease. Potential mechanisms by which the fibrin rich provisional matrix appears in healing wounds are presented. MATERIALS AND METHODS: Methodologies, such as in situ hybridization, immunolocalization and labeled tracer techniques, were used in our study. RESULTS: We found by these approaches that the 2 general mechanisms that contribute to the generation of the wound extracellular matrix are leakage of plasma proteins, such as plasma fibronectin and fibrinogen, and the synthesis of variants of fibronectin by wound cells. CONCLUSIONS: Developing an understanding of the mechanisms that regulate the appearance of these matrix proteins may provide new avenues for therapy in conditions such as Peyronie's disease in which the temporal pattern of the provisional matrix deposition is abnormal.
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In rats operated with large excisional skin wounds which were not treated with zinc tape, the serum zinc concentration was decreased at every observation time during the first post-operative day and the absorption of zinc from the intestine was increased. Slight decreases in the zinc concentration were seen in some tissues while liver zinc was very high. In rats with wounds treated with zinc tape, serum zinc was markedly increased at 6 hours, lower but above control levels at 7 and 12 hours and markedly increased again at 24 hours. The absorption of zinc from the intestine was low. Zinc concentration were elevated in most tissues sampled; they were high in testis and kidney and very high in liver. The results strongly indicate that the operative trauma and/or acute inflammatory conditions in the wounds in animals not treated with zinc tape initiate a movement of zinc from serum, some tissues and the content of the intestine to the liver. In the zinc tape treated group the increase in liver zinc was supplied mostly by the zinc tape. It is assumed that these large increases in zinc concentration in the liver are the result of the incorporation of zinc into certain zinc containing proteins which are produced in response to the inflammatory process in the wound. An increase was also found in the copper concentration in the liver of zinc tape treated animals and a decrease in the iron concentration in the liver of both groups of operated animals compared to controls.
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Severe trauma impairs host immunity, which in turn renders the host susceptible to infection often terminating in death. This impairment occurs 7 to 14 days after injury, a time when wound healing is at its maximum. We examined the interactions of wound healing to host immunity by studying the in vitro and in vivo immune effects of wound components (i.e., wound fluid [WF] and wound mononuclear cells [WMNC]). Lewis male rats (RT-1(1] weighing 300 to 350 gm underwent 7 cm dorsal skin incisions and subcutaneous placement of polyvinyl alcohol sponges. At 7 and 10 days after wounding, sponges were removed and WF was separated from the cellular elements. The cell suspension was purified to contain 80% to 90% WMNC. Ten percent WF from 7- and 10-day-old wounds inhibits normal thymic lymphocyte blastogenesis to concanavalin A and phytohemagglutinin. Addition of 5 X 10(4) WMNC leads to similar inhibition. WF and WMNC from 10-day-old wounds also inhibit in vitro allogeneic responses tested in one way MLR of Lewis splenocytes with inactivated ACI (RT-1a) spleen cells by 75% to 96% and 85% to 98%, respectively. The inhibitory action of WF is heat resistant (56 degrees C for 30 minutes) and noncytotoxic. In vivo allogeneic responses, tested by grafting ACI skin onto Lewis recipients, were inhibited by intraperitoneal administration of 10-day-old WF (p less than 0.01). We conclude that WF contains factor(s) that inhibit in vitro and in vivo immune responses. WMNC exhibits the same action, suggesting that they may be the source of the WF inhibitory factor(s). These findings may explain host immunosuppression after severe trauma.
PURPOSE: Vacuum-assisted closure (VAC), originally developed as an adjunct to wound care, has gained popularity in managing complex, chronic wounds. This study was designed to compare VAC with traditional saline-wet-to-dry (WD) dressings on acute wound healing in a pig model. METHODS: Nine animals were divided into groups of 3. Three rows of 2, 4-cm diameter circular defects were excised on each animal. Vacuum-assisted closure therapy was applied to 2 adjacent wound beds, WD dressings were applied to 2 adjacent wound beds, and ventilated transparent dressing covered the 2 remaining wounds as controls. Random members from each group had their wounds harvested on postoperative days (POD) number 4, 7, and 9, respectively. The specimens were histopathologically evaluated and graded with regard to immature granulation tissue, mature granulation tissue, necropurulent surface crust, proliferating cell nuclear antigen (PCNA), and collagen deposition. RESULTS: The WD-treated wounds had less necropurulent material on the surface compared with the VAC and control groups (p < 0.05). Day 9 specimens demonstrated increased immature collagen in the VAC and WD groups compared with control. No other statistically significant variations existed between the treatment groups. CONCLUSIONS: Under the conditions of this study, the histopathologic observations do not support more rapid wound healing for the acutely injured VAC-treated wound compared with the WD-treated wound in young healthy pigs.
BACKGROUND: Keratinocyte growth factor-2 (KGF-2) also described as fibroblast growth factor-10 (FGF-10) is a newly identified member of the fibroblast growth factor family. KGF-2 is 96% identical to the recently identified rat FGF-10 and specifically stimulates growth of normal human epidermal keratinocytes. The present study was undertaken to examine the effects of topically applied KGF-2 in an incisional wound healing model. KGF-2 treatment resulted in an improvement in incisional wound healing as characterized by an increase in breaking strength, collagen content, and epidermal thickness. METHODS: KGF-2 was topically applied to linear incisions made in the dorsal skin of Sprague-Dawley rats. Biomechanical testing was done using an Instron tensiometer for breaking and tensile strength determinations. Wound collagen content was determined using the Sircol collagen assay. Epidermal thickness measurements were conducted using Masson's trichrome-stained sections of the wound. RESULTS: A single topical application of KGF-2 at the time of wounding resulted in an increase in wound breaking and tensile strength at Day 5 after wounding. Breaking strength of KGF-2-treated wounds was significantly higher compared with the buffer control (1 microgram, 222.1 +/- 13.5 g, P = 0.0007; 4 microgram, 248.7 +/- 15.4 g, P = 0.0001; 10 microgram, 247.2 +/- 21.9 g, P = 0.001; buffer, 141.0 +/- 9.7 g). Epidermal thickness and wound collagen content were significantly increased following treatment with KGF-2. CONCLUSIONS: Based on our findings, KGF-2 is a potent stimulator of wound healing as demonstrated by increased mechanical strength accompanied by an increase in wound collagen content. KGF-2 could be an important cellular mediator responsible for the initiation and acceleration of wound healing and may enhance the healing of surgical wounds.