Zone Of Stasis Research Articles

Copper Ions Ameliorated Thermal Burn-Induced Damage in ex vivo Human Skin Organ Culture

Introduction: The zone of stasis is formed around the coagulation zone following skin burning and is characterized by its unique potential for salvation. The cells in this zone may die or survive depending on the severity of the burn and therefore are target for the local treatments of burns. Their low survival rate is consistent with decreased tissue perfusion, hypotension, infection, and/or edema, resulting in a significant increase in the wound size following burning. Copper is an essential trace mineral needed for the normal function of almost all body tissues, including the skin. Objective: The aim of the work was to study the effect copper ions have on skin burn pathophysiology. Methods: Skin obtained from healthy patients undergoing abdominoplasty surgery was cut into 8 × 8 mm squares, and round 0.8-mm diameter burn wounds were inflicted on the skin explants. The burned and control intact skin samples were cultured up to 27 days after wounding. Immediately following injury and then again every 48 h, saline only or containing 0.02 or 1 µM copper ions was added onto the skin explant burn wounds. Results: We found that exposing the wounded sites immediately after burn infliction to 0.02 or 1 µM copper ions reduced the deterioration of the zone of stasis and the increase in wound size. The presence of the copper ions prevented the dramatic increase of pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) and transforming growth factor beta-1 that followed skin burning. We also detected re-epithelialization of the skin tissue and a greater amount of collagen fibers upon copper treatment. Conclusion: The deterioration of the zone of stasis and the increase in wound size following burning may be prevented or reduced by using copper ion-based therapeutic interventions.

The healing effect of pulsed magnetic field on burn wounds

A burn is one of the most difficult injuries people can face.The primary pathology is coagulation necrosis resulting from tissue damage.Many wound care products have been developed to be used in situations such as the poor general condition of the patient and lack of solid area to be grafted. However, the high costs of these products make their use complicated.In this study, the effect of PEMF on cutaneous wound healing in an animal burn model was evaluated and the dose and duration of the magnetic field should be discussed for this effect to occur. Animals were divided into five groups including eight each (n = 40) (Groups 1, 2, 3, 4, 5).Group 1 was the control group; received no treatment after second-degree burn wound. Group 2 received daily wound care with saline. Group 3 received daily wound care with pomade containing mupirocin. Group 4 received Pulsed Electromagnetic Field signal for 60 min (1.5 m T and 40 Hz for seven days and Group 5 also received PEMF signal for 60 min the same frequency and intensity for14 days. Microscopically, second-degree burn wounds were successfully detected in all rats. Histopathological examination results in no significant difference between groups in neutrophil infiltration. The difference between the groups in vascularization was statistically significant between Group II and Group V (p < 0.001) and between Group I and Group V (p = 0.005) Epithelialization was present in 75% of the rats in Group V, while no epithelialization was observed in any of the other groups. In conclusion, we observed a significant improvement in the stasis zone of the group receiving Pulsed Electromagnetic Field for two weeks.

N-asetilsistein ve ozon gibi antioksidan ilaçların staz zonu üzerindeki etkinliği

Title: The effectiveness of antioxidant drugs such as N-acetylcysteine and Ozone on the stasis zone. Short title: Effectiveness of N-acetylcysteine and Ozone on the stasis zone. Purpose: Stasis zone, the zone around the coagulation zone, is important for the prevention necrosis in burns. Various drugs were studied in literature to prevent necrosis in stasis zone. The previous researches have shown the effectiveness of Nacetylcysteine treatment on both remote organs and local side in thermal injury. Demonstration of the effectiveness of N acetylcysteine and Ozone on stasis zone prevention in thermal injury was the goal of this study. Methods: For this purpose, 24 4-month-old Wistar albino type female rats weighing 200±20 g were used in the study. Compound burning model was made in these rats. Next, the compound was applied to the combustion model to compare the effectiveness of N-acetylcysteine and Ozone. To identfy histopathological destruction severity a scoring method was applied. Malondialdhyede (MDA), Glutathione Peroxidase (GPx), Superoksid dismutase (SOD), and catalase (CAT) levels were analyzed in serum samples of the rats to find out the alterations in the balance between oxidatitaion and antioxidation system. Results: While the highest MDA levels were observed in group I, the decrease was significant in group II and III (p=0.03 and p<0.02). SOD levels were significantly higher in group III compared to group II (p<0.05). CAT levels were higher in group II and III than group I (p<0.001, p<0.001). GPx levels were higher in group II (p<0.001), and group III (p<0.001). Histopathological scores were lower in group III than group I (p=0.001). Conclusion: This study showed that both Ozone and N-acetylcysteine are effective agents in rescuing the stasis site. It was also concluded that Ozone might be more beneficial than N-acetylcysteine.

134 The Effect of Adipose Derived Stromal Vascular Fraction on Stasis Zone in an Experimental Burn Model on Streptozocin – Induced Diabetic Rats

Abstract Introduction Stasis zone is the encircling area of the coagulation zone which is a critical area determining the depth and width of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Methods Intraperitoneal Streptozotocin was administered for the induction of diabetes mellitus (DM) and the development of DM was confirmed by the measurement of blood glucose levels in the blood samples with blood glucometer weekly 48 hours after injection. Rats with blood glucose levels above 200 mg/dl were accepted as diabetic. The diabetic animals were followed for 4 weeks before the intervention. Thermal injury was applied on dorsum of diabetic Sprague – Dawley rats (n=20) according to the previously described ‘‘comb burn’’ model. After the burn injury (30 minutes) on Sprague - Dawley rats; rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of diabetic Sprague - Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density and gradient of fibrosis were determined via immunohistochemical assay. Results Macroscopic stasis zone tissue survivability percentage (32 ± 3.28 %, 57 ± 4.28 %), average number of vessels (10.28 ± 1.28, 19.43 ± 1.72), capillary count (15.67 ± 1.97, 25.35 ± 2.15) and vascular density (1.55 ± 0.38, 2.14 ± 0.45) were higher on ADSVF side. Fibrosis gradient (1.87 ± 0.51, 1.50 ± 0.43) and inflammatory cell density (1.33 ± 0.40, 1.20 ± 0.32) were higher on the PBS side. Conclusions Macroscopic and microscopic findings determined that ADSVF has a statistically significant benefit for salvaging stasis zone on acute burn injuries in DM.

Comparison of the Effects of Stem Cell, Platelet Rich Plasma and Ovarian Follicle Fluid on Burn Stasis Zone (Experimental Study)

Objective: The basic aim in the treatment of second-degree burns is to prevent progressive cell death, and so treatments are directed at the zone of stasis. In this study, We were aimed to investigate the healing effects of using Mesenchymal Stem Cells (MSCs), Ovarian follicular fluid (OFS) and Platelet-rich plasma (PRP) on burn stasis zone in an experimental burn model. Method: Forty rats were divided randomly into four groups. Burns were created in each group according to the comb burn model. The control group received no treatment; the mesenchymal stem cell [MSC] group received MSC; the platelet-rich plasma [PRP] group received PRP; and the ovarian follicular fluid [OFF] group received OFF subcutaneously on days 1, 3 and 5. On days 1 and 21, all rats were photographed and the burn sites were calculated. At the end of day 21, all rats were sacrificed, the dorsum containing the created burns were excised, and the epithelialization, collagen amount, fibroblast density, inflammatory cell density and VEGF amounts were evaluated histopathologically. Results: The groups were assessed based on the burn site healing rate and histopathological scoring. Healing was faster in the MSC group [p<0.005], PRP group [p>0.005] and OFS group [p<0.005] than in the control group. When the treatment groups were compared with each other, the best healing was observed in the MSC, PRP and OFF groups, respectively. Conclusions: MSC, PRP and OFF were found to have a positive effect on burn healing, with MSC being the most efficient method among the three, followed by PRP and OFF, respectively, which were found to provide a faster healing than the control group.

ASMq protects against early burn wound progression in rats by alleviating oxidative stress and secondary mitochondria‑associated apoptosis via the Erk/p90RSK/Bad pathway.

Burn wounds present an evolutionary progression, in which the initial wound tissue deepens and expands following thermal injury. Progressive tissue damage in the zone of stasis may worsen burn injury, which is associated with oxidative stress and secondary apoptosis, and worsen the prognosis of patients with burn wounds. The mitochondrial apoptotic pathway is involved in receiving oxidative signals and regulating tissue apoptosis. Previously, Abnormal Savda Munziq (ASMq), a natural compound of traditional Uyghur Medicine, which includes ten types of herb, has been reported to exhibit a number of effects, including anti-inflammatory, antioxidative and anti-apoptotic activities. The present study demonstrated that ASMq protected against early burn wound progression following thermal injury in rats; this effect may be mediated by its ability to attenuate oxidative stress-induced mitochondria-associated apoptosis. The present study may provide a novel therapeutic method to prevent early burn wound progression following burn injury.

The Effects of Systemic Use of Epigallocatechin Gallate in Thermal Injury Progression

The burn wound progression is a complex process caused by inadequate tissue perfusion, free radical damage, and altered cytokine levels in burn patients. Epigallocatechin gallate (EGCG) has vasodilator, antioxidant, and skin protective properties. In this study, we investigated the effects of epigallocatechin gallate (EGCG) on burn wounds. Nine male Wistar albino rats were randomly assigned to the control group and received no burn insult. The other rats were exposed to thermal injury with a brass comb and randomly divided into two groups: burn with no further treatment (group 1, n:3) and burn with enteral EGCG treatment (group 2, n:3). The administration of EGCG was initiated 5 min after the burn procedure at a dose of 1 mg/kg by gastric lavage and repeated for 3 days at an infusion rate of 1 mg/kg/day. Skin sections were stained with Hematoxylin-Eosin and Masson’s trichrome for histochemistry. The primary antibodies used for immunohistochemistry included rabbit anti-4-hydroxynonenal (protein-HNE), rabbit anti-malondialdehyde (protein-MDA, mouse monoclonal anti-acrolein (protein-ACR), rabbit anti-ALDH1A1, and rabbit anti-ALDH2. Systemic administration of EGCG after burn injury significantly ameliorated the histological alterations in burn sites, especially in the zone of stasis. The expression of reactive aldehyde products (HNE, MDA, ACR) as a result of thermal injury significantly decreased in the EGCG group. EGCG reduced reactive aldehyde products independent of ALDH1 and ALDH2 pathway and improved histological alterations with cytoprotective and antioxidant effects. Early systemic use of EGCG prevents burn wound from progressing to deep structures and limits its extension to the adjacent zones.

Locally activated mitophagy contributes to a “built-in” protection against early burn-wound progression in rats

AimsDeep burn-wounds undergo a dynamic progression in the initial or periburn area after insults, and the zone of stasis is the crucial region suffering the deterioration, considered as salvageable. Few studies explored the role of mitochondria in this process. This study is to clarify a possible “built-in” protection of mitophagy. Main methodsA classic “comb” scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission-electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator. Key findingsWe found that burn-caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was involved in the aforementioned changes. Furthermore, we detected mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. SignificanceWe demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a therapeutic target due to its possible regulation on BNIP3- or PARKIN-mediated mitophagy.

Locally Activated Mitophagy Contributes to a 'Built-In' Protection Against Early Burn-Wound Progression in Rats Following a Regulation of HIF-1α

Backgrounds: Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults. The zone of stasis has a higher risk of deterioration and is considered a salvageable target. Few studies have explored the role of mitochondrial damage in this process and potential “built-in” self-defense within the human body. Methods: A classic “comb” scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy happened in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator. Findings: We found that burn insults caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was also involved in the aforementioned changes. Furthermore, we detected typical mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. Interpretation: Accordingly, burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a more beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a potential therapeutic target due to its possible regulatory effects on BNIP3- or PARKIN-mediated mitophagy. Funding Statement: This work was supported by the following grants: National Natural Science Foundation of China (NSFC) Grants 81671909, 81901958 and Zhejiang Provincial Natural Science Foundation of China Grants: LY18H150004, LY19H150004, LY20H150010. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The present study was performed according to protocols approved by the Committee on Animal Care and Use of the Second Affiliated Hospital Zhejiang University School of Medicine (2019-331), and strictly followed the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.

Modification and utility of a rat burn wound model.

This study aimed to improve the conventional rat burn wound model and to validate its utility. In total, 60 Sprague-Dawley rats were divided equally into the control and experimental groups. Altogether, 60 burn wound models with zones of stasis were created in each group. Gross visual assessments of the burn wounds were performed at 0, 24, and 48 hours after burn creation. The rates of necrosis in the zones of stasis were calculated, and the blood flow from the wounds was examined. Wound tissues were collected 48 hours after the burn and subjected to hematoxylin and eosin staining to determine whether the models were successfully established. The model success rates were calculated. The success rate of the burn wound models was significantly different between the control group and the experimental group (93.33% [56/60] vs 100%; P = .042). The Cronbach's alpha values and the respective correlation coefficients indicated that the stability of the zones of stasis in the models on the two sides of the spine was higher in the experimental group than in the control group. The standard deviations of the rate of necrosis, blood flow, and density of necrotic cells and apoptosis cell density, and inflammatory factor content in the zones of stasis were smaller in the experimental group than in the control group at 48 hours after model construction. This suggested that the stability of repeated procedures was higher in the experimental group than in the control group. The novel device for creating burns in animal models facilitated the effective creation of zones of stasis for rat burn wound models. Both the model success rate and stability were higher compared with the conventional model construction method. In addition, the use of the novel device can better align with the requirements of self-controlled studies.

Antioxidants Reduce Tissue Necrosis in The Zone of Stasis: Review of Burn Wound Conversion

Summary: Severe burns are devastating condition identified by loss of hemodynamic stability and intravascular volume. Adequate fluid replacement, nutritional support, and immediate wound grafting can reduce the risk of infection and mortality. Oxidative stress was shown to have significant role in the burn wound conversion, which happens when the zone of stasis can’t be salvaged and progresses to necrosis. Decreasing the level of oxidative stress early may be fundamental in reducing burn injury progression into deeper tissue. Several animal studies have demonstrated the advance of antioxidant supplementation for burns outcomes. Approach to this salvageable burn tissue is a breakthrough for new directions in burn management. Antioxidant supplementations was proven to prevent burn conversion on the ischemic zone. Administering antioxidant post-burn is linked with less progression of burn depth and inflammatory cytokine release, which alleviates burn-related morbidity and mortality and improves patient’s quality of life. To date, no clinical trials have been done to reproduce similar outcomes of this ROS-scavenging therapy as successfully observed in murine models. Antioxidant supplementation is a promising treatment avenue to halt burn wound conversion following severe burns.&#x0D; Keywords: Burn wound, wound conversion, burn management, antioxidant

Secreted responses of umbilical cord mesenchymal cells to full thickness swine burns are refined by the zone of injury

Background & Aim Primary treatment of battlefield burns is often inadequate due to delayed field evacuation or limited care in mass casualty incidents. Untreated burns expand in depth and surface area and elicit a hyper-immune response until the damaged tissue is removed. Third degree (full-thickness) burns penetrate the dermis and comprise 3 concentric zones of injury. The central zone of coagulation is irrevocably damaged while the surrounding zone of stasis is at risk. Tissue in the outermost zone of hyperemia can be saved despite an acute inflammatory response and increased perfusion. Mesenchymal stromal cells (MSCs) reportedly improve outcomes as post-surgical burn treatments. We assessed in vitro whether MSCs may also benefit burn sequelae if applied prior to surgical intervention. Methods, Results & Conclusion Nine anaesthetized swine received 3rddegree burns on the inner flank by a heated brass bar. After 30 minutes, the burn was excised ∼1 cm outside the zone of hyperemia. Control (unburned) samples were also excised. The burn center (zones of coagulation and stasis) and margin (zone of hyperemia) were isolated by dissection. Human umbilical cord MSCs (UC-MSCs), were co-incubated with 0.4 +/- 0.005g of tissue using a 6-well Transwell system for 24, 48 or 72 hours (h) in xeno-free media. Secreted proteins were assessed by multiplex ELISA of 115 analytes. Within 24h of exposure to any burn tissue, UC-MSCs increased output of inflammation mediators including fractalkine, GCP-2, GRO-β, I-309, IL-19, MCP-3, MIP3-α, MMP-2 and TSLP. IL-2Ra and MIG were specifically elevated in response to the necrotic center tissue, followed by β-NGF and IL-3 at 48h and SCF and SCGF-β at 72h. Intriguingly, the burn margin stimulated production of wound healing molecules in addition to inflammation mediators. G-CSF, HGF, IL-1β, IL-1RA, LIF and TECK increased significantly at 24 hours, followed by IL-20, IL-35, MDC, sCD163 and sTNF-R1 at 72h. Thus, UC-MSCs exhibit refined soluble responses that may improve outcomes for severe burn patients that initially receive sub-optimal treatment and delayed definitive care. The observed zone-specific responses suggest that the molecular mechanisms of MSC treatments may differ if the cells are applied before or after surgical debridement and depending on their localization within the wound. UC-MSCs delivered to unsalvageable tissue can produce a response focused on managing inflammation, while UC-MSCs delivered to the viable peripheral zone additionally promote wound healing.

Connexin 43 upregulation in burns promotes burn conversion through spread of apoptotic death signals.

Burn wounds continue to worsen after initial injury in a process known as burn conversion, which lasts about 3-5 days. It causes burn wounds to enlarge and deepen, leading to greater morbidity. Apoptosis is one of the factors contributing to the conversion of the zone of stasis into the zone of coagulation. Suppression of apoptosis has been associated with reducing burn conversion. Connexin 43 (Cx43) gap junctions facilitate the spread of apoptotic signals from dying cells to healthy neighbouring cells in injured tissues through the bystander effect. The study is to understand the role of Cx43 in burn conversion. In our study, 15 burn tissue samples were arranged into three groups as early (beginning of burn conversion), intermediate (extensive burn conversion) and late (established burn conversion) burns. We found a striking increase in the amount of Cx43 protein expressed in the dermal fibroblasts (identified with heat shock protein 47 (HSP47) staining) in the zone of stasis in early and intermediate burns. These dermal fibroblasts also express high levels of cleaved-Caspase 3 indicating on-going apoptosis. Our findings suggest that elevation of Cx43 may play an active role in burn conversion spreading apoptosis in the early and intermediate burn wound.

Qualitative analysis of surgical smoke produced during burn operations.

Burned tissue is necrotic and it is surrounded by a zone of stasis and hyperaemia with changed cell metabolism. The removal of burned tissue using an electric knife releases large amounts of surgical smoke. The aim of the research was to analyse volatile, nonpolar, organic compounds that are released during the excision of burned tissue using an electric knife (mono- and bipolar). The study includes analysis from 40 solid-phase microextraction (SPME) fibres, exposed during 10 interventions (6 escharotomy and 4 necrectomy). The analysis of volatile compounds was performed using mass spectrometry gas chromatography (GCxGC-ToFMS).The total analysis covered 432 compounds, whereas after the removal of the "background" compounds - 153 volatile organic substances remained. The analysis of surgical smoke showed that, including derivatives, benzene constituted as much as 17.65% of all of the studied compounds. Cyclic compounds constituted on average 22.5% of the analysed substances, out of which cycloheptatrien constituted 20.26%. Alkanes, alcohols and their derivatives constituted nearly 25% of volatile organic compounds, with chloromethane constituting as much as 13.7%. Permutational multivariate analysis of variance (PERMANOVA) revealed statistically significant differences between escharotomy and necrectomy patients (F(1.9) = 5.91, p = 0.007).Our study revealed the presence of complex toxic hydrocarbon derivatives in surgical smoke. We also observed that the content of surgical smoke is different depending on the type of the conducted intervention. So far, no studies focusing on hazards posed by surgical smoke that is released during the resection of burned tissue are in the literature.

The effects of sildenafil and N-acetylcysteine the zone of stasis in burns.

In burn wound healing, zones of burn, namely zone of hyperemia, the zone of stasis, and zone of coagulation, have crucial importance. These zones have been identified based on the pathophysiology of the burn, and treatment of burn has been improved. The zone of necrosis is treated by excision and repair through grafting. Zone of stasis fully recovers in 24-48 h if the burn treatment is managed well. Otherwise, it may convert to a zone of coagulation. Hyperemia zone is a zone that recovers itself. Recovery of the zone of stasis is very critical in burn treatment. Active oxygen radicals produced due to the hypermetabolism due to burn wounds are known to speed to the process of the zone of stasis converting into the zone of coagulation. The present experimental study aims to evaluate the effects of sildenafil and N-acetylcysteine on the zone of stasis and to establish whether they had any contribution to wound healing in burns. In the present study, 32 four months old female Wistar Albino rats with 200±20 gr body weights were used. The rats were divided into four groups as the sham group (Group 1), the intraperitoneal group (Group 2), Sildenafil group (Group 3, intraperitoneal 10 mg/kg for 10 days), N-acetylcysteine (Group 4, intraperitoneal 100 mg/kg for 10 days). Tissue samples were collected for serum and cytopathology studies of the Malondialdehyde level, glutathione peroxidase, superoxide dismutase, and catalyze enzyme activity. All the rats were sacrificed on the 10th day of the tests edema, hyperemia, epithelial degeneration, necrosis, inflammatory infiltration and fibrosis measurements were made. When compared with the controls, both of the treatment groups had lower tissue damage scores. MDA level was lower in Group 3 and 4 compared to Group 2 and lower in Group 3 compared to Group 4. SOD, catalase and GPH-Px levels were higher in Group 3 and Group 4 compared to Group 2 and higher in Group 3 compared to Group 4. The results of our study conducted on an experimental burn model created by rats support that Sildenafil and N-acetylcysteine have positive effects, such as decreasing oxidative stress level and increasing wound healing in burns. Further experimental studies are required on this subject.

The effects of melatonin on the healing of burn wounds in pinealectomized rats.

The present study aims to investigate the favorable effects of melatonin on burn wound healing in rats. In this study, forty Wistar-albino-type male rats were divided into four groups. Group 1 was the control group, Group 2 rats were treated using exogenous melatonin, Group 3 rats were pinealectomized, and Group 4 rats were pinealectomized then treated with exogenous melatonin. In all groups, a deep second-degree burn was created on the backs of the rats with a metal plate heated in boiling water. We monitored the progress of burn healing for seven days. At the end of them, we evaluated hydroxyproline levels, type III collagen, edema, inflammatory infiltration, congestion, vascular proliferation, fibrosis, the thickness of the zone of stasis and the epithelium to assess the progress of healing. The zone of stasis was less thick in Group 2 than the other groups (p=0.009). Type III collagen dyeing (p=0.031), fibrosis (p=0.011) and edema (p=0.031) were higher in Group 2 than the other groups. Congestion was higher in the control group than Group 4 (p=0.031). Other evaluated parameters showed no significant differences among the groups. In this study, it was noted that once total melatonin levels exceeded a certain threshold, a preventive effect was exerted on burn wound damage progression by reducing the zone of stasis. Melatonin may also prevent the development of hypertrophic scarring. Melatonin may be a potential therapeutic option that can supplement traditional treatment in burn wounds; however, further studies with higher doses of exogenous melatonin administered over longer periods are needed to further evaluate the effects noted in this study.

The effects of epidermal growth factor on early burn-wound progression in rats.

After burns, protecting tissues by medicines in the zone of stasis reduces the width and depth of injury. This study's goal was to reduce burned tissue damage in the zone of stasis using epidermal growth factor (EGF). Forty-eight Wistar rats were separated into three groups. In all groups, the burn procedure was applied following the comb burn model. In Group 1, no postburn treatment was administered. In Group 2, physiological saline solution (0.3 cc) was injected intradermally and in Group 3, EGF (0.3 cc) was injected intradermally into stasis zone tissues after the burn procedure. Surviving tissue rates were 24.0% in Group 1, 25.3% in Group 2, and 70.2% in Group 3. The average numbers of cells stained with Nrf2, HO-1, and the number of apoptotic cells were 230, 150, and 17.5 in Group 1, 230, 145, and 15.0 in Group 2, and 370, 230, and 0 in Group 3, respectively. Values in Group 3 were found to be statistically significantly different than those of Groups 1 and 2; there was no difference between Groups 1 and 2. This study shows that EGF protects zone of stasis tissue from burn damage.

The effect of platelet-rich plasma in inactive form on the burn zone of stasis in rats

The protection of the burn stasis zone tissues (BSZT) reduces the width and depth of the burn injury. In this study, it is aimed to show the effect of platelet-rich plasma (PRP) on the burn zone of stasis. Seventy-two Wistar rats were used in the study. PRP was obtained from the blood taken from eight rats. The remaining 64 rats were divided into four groups. In Group 1, only the burn procedure was performed. In Group 2, 0.3 cc of physiological saline solution, in Group 3, 0.3 cc of platelet-poor plasma and in Group 4, 0.3 cc of PRP were intradermally injected into BSZT after burn procedure. 21.5% of the tissues in Group 1, 20.8% in Group 2, 27.0% in Group 3, and 69.6% in Group 4 were found to be alive. The autophagic cell number average was calculated as 340 in Group 1, 340 in Group 2, 335 in Group 3 and 450 in Group 4, while the average number of cells stained with Nrf2 was calculated as 225 in Group 1, 245 in Group 2, 250 in Group 3 and 370 in Group 4. When the groups were compared in terms of the living tissue ratio, autophagy and number of cells stained with Nrf2, the values in Group 4 were found to be statistically significantly higher compared to Group 1, Group 2 and Group 3, while there was no difference between Groups 1, 2 and 3. This study has shown that PRP has a protective effect on BSZT.

Salvaging the Zone of Stasis in Burns by Pentoxifylline: An Experimental Study in Rats.

Surrounding the zone of coagulation is the zone of stasis, which is characterized as a mix of viable and nonviable cells, capillary vasoconstriction, and ischemia. Saving the zone of stasis is a major subject of the burn wound studies. If pathological changes in the zone of stasis can be minimized, conversion of burn wounds may be prevented. The aim of this study was to investigate the effects of pentoxifylline (PTX) on the zone of stasis in burns and burn wound healing. Twenty Sprague-Dawley rats were used in this study. Comb model was used to create zone of stasis in burns. Treatment group received a total of 200 mg/kg/d of PTX in two equal doses intraperitoneally whereas isotonic saline solution was given intraperitoneally to the control group. This treatment was continued until postburn day 17. Tissue samples were taken from the burn wounds on postburn days 3, 7, and 17. Fibroblastic and vascular density, inflammatory cells, re-epithelialization rates were assessed in histopathological study. Furthermore, macroscopic healing of burn areas on the right side were compared between the groups by taking pictures on postburn day 17. PTX treatment decreased inflammation of the burn wound in the early postburn period. Comparing the necrotic area between the groups, PTX apparently had lower rate of necrosis. PTX treatment increased re-epithelialization of burns wounds. Our study concluded that systemic treatment of burns by PTX enhances burn wound healing and helps salvaging the damaged but live cells in the zone of stasis by increasing the rate of epithelization, decreasing the necrotic area and preventing the deepening of the burn wound.

The effects of nitroglycerin in the zone of stasis in a rat burn model.

Studies evaluating the recovery of the zone of stasis is an important issue in burn research. In this study, we aimed to evaluate and compare the efficiency of an anti-ischemic and vasodilatory agent, a topical agent containing 2% nitroglycerin with 1% silver sulfadiazine, and bacitracin-neomycin sulfate in the zone of stasis histomorphologically and immunohistochemically. We conducted an experimental study using 30 Wistar-Albino rats, each weighing 250-300 grams. The rats were divided randomly into five groups (six rats in each group). In this study, the "comb model," which was deemed to be the most appropriate experimental model to produce an injury with predictable zones and was first described by Regas and Erhlich, was used. The following were applied to the zone of stasis after creating a burn model in 0, 24, and 48 hours: topical 2% nitroglycerin, 1% silver sulfadiazine, bacitracin-neomycin sulfate, and Vaseline-lanolin (sham). After 72 hours, biopsies were performed from the zone of stasis and evaluated by histomorphological and immunohistochemical CD 34 (expressed in human endothelial and hematopoietic cells) and D 2-40 (expressed in the endothelium of lymphatic capillaries) methods. The results were evaluated using the chi-square test. Compared with the other groups, a statistically significant difference was found in edema, inflammation, and vascular proliferation in the nitroglycerin group. Significantly more intense staining for CD 34 was found in the nitroglycerin group compared with the other groups. Immunohistochemical staining for D 2-40 was also found statistically significant in the nitroglycerin group (p<0.05). A topical containing 2% nitroglycerin increases vascular proliferation in the zone of stasis affects the recovery and may be used as a new agent in burn injury treatment.