Pharmaceutical Preconditioning With Nitric Oxide Synthase and L-Arginine in Ischemic Tissues.

BACKGROUND: Nitric oxide (NO) is a multifunctional signaling molecule involved in regulating vascular tone and tissue oxygenation. It is also an important cytoprotective agent against ischemia-reperfusion injury (IRI). Enhancing NO bioavailability via exogenous NO synthases (NOSs) and L-arginine promotes conversation to NO, circumventing the problem of nonfunctioning NOSs under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of neuronal, inducible, and endothelial NOS and L-arginine on reperfusion-induced skin flap alterations. METHODS: The vascular pedicle isolated rat skin flap model was used and underwent 3 hours of ischemia. At 30 minutes before ischemia, normal saline, endothelial-, inducible-, and neuronal NOSs (1/2 IU) and L-arginine (100 mg/kg body weight) were administered by means of intravenous infusion. The IRI-induced alterations were measured 5 days after the operation. RESULTS: The 3 isoforms of NOS increased the flap vitality rate (VR) from 10% to 23% compared with the control group. L-Arginine treatment also increased the VR by approximately 15%. The combination of L-arginine with NOS resulted in even higher flap VRs. The best results could be achieved with the combination of endothelial NOS (2 IU) and L-arginine. CONCLUSIONS: Modulation of NO bioavailability via exogenous application of NOSs and L-arginine significantly improved VRs in a skin flap rat model. This pharmacologic preconditioning has the potential to attenuate IRI-induced alterations in skin flaps.

Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1.

BACKGROUND: The mechanisms influencing the balance of nitric oxide (NO) bioavailability in tissues are negatively affected under diabetic and also under ischemic conditions. Free tissue transplantation for diabetic patients has to deal with both ischemic and diabetic circumstances, which lead to a significantly decrease in providing NO, thus increasing ischemia-reperfusion injury. In previous studies, we could prove that enhancing NO bioavailability leads to attenuated ischemia-reperfusion injury macrocirculatory and microcirculatory alterations in healthy and also in diabetes type 2 rats. This study is evaluating the role of inducible nitric oxide synthase in different dosages and L-arginine under diabetes type 1 conditions. METHODS: Diabetic type 1 conditions were established via streptozotocin over a period of 4 weeks and verified via blood sugar, insulin, and C-peptide levels. Vascular pedicle isolated rat skin flap model that underwent 3 hours of ischemia was used. At 30 minutes before ischemia, normal saline, inducible nitric oxide synthase (NOS) (1/2 IE), and L-arginine (50 mg/kg body weight) were administered systemically. Ischemia/reperfusion (I/R)-induced alterations were measured 5 days after the operation. RESULTS: The inducible NOS (iNOS) attenuated I/R-induced alterations under diabetic type 1 conditions significantly with vitality rates of 16.1% compared with control group (5.5%). Best results could be achieved with the combination of iNOS (1 IE) and L-arginine displaying vitality rates of 43%. Increased dosage of inducible nitric oxide (2 IE) led to decreased vitality rates (22.2%/27.4% without/with L-arginine). CONCLUSIONS: Supporting the mechanisms of NO bioavailability via exogenous application of iNOS and L-arginine significantly attenuated I/R-induced alterations in a skin flap rat model. This pharmacologic preconditioning could be an easy and effective interventional strategy to uphold conversation of L-arginine to NO even on ischemic and type 1 diabetic conditions.

Extracorporal Shock Wave Therapy Enhances Receptor for Advanced Glycated End-Product-Dependent Flap Survival and Angiogenesis.

BACKGROUND/OBJECTIVES: Loss of skin flaps due to deteriorated wound healing is a crucial clinical issue. Extracorporal shock wave therapy (ESWT) promotes flap healing by inducing angiogenesis and suppressing inflammation. The receptor for advanced glycation end-products (RAGEs) was identified to play a pivotal role in wound healing. However, to date, the role of RAGE in skin flaps and its interference with ESWT are unknown. METHODS: Caudally pedicled musculocutanous skin flaps in RAGE and wt mice were treated with low-dose extracorporal shock waves (s-RAGE, s-wt) and analyzed for flap survival, histomorphologic studies, and immunohistochemistry during a 10-day period. Animals without ESWT served in each genotype as a control group (c-RAGE, c-wt). Statistical analysis was carried out by repeated-measures analysis of variance. RESULTS: Flap necrosis was significantly reduced after ESWT in wt animals but increased in RAGE-deficient animals. Morphometric differences between the 4 groups were identified and showed a delayed wound healing with dysregulated inflammatory cells and deteriorated angiogenesis in RAGE animals. Furthermore, spatial and temporal differences were observed. CONCLUSIONS: The RAGE controls inflammation and angiogenesis in flap healing. The protective effects of ESWT are dependent on intact RAGE signaling, which enables temporary targeted infiltration of immune cells and neoangiogenesis.

ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model.

BACKGROUND: Due to their unique properties, adipose derived stem cells (ADSCs) obtain promising potential to enhance nerve regeneration. The aim of this study was to investigate if fibrin-glue embedded ADSCs were a beneficial adjunct to primary coaptation in a rat sciatic nerve model. MATERIALS AND METHODS: Fifty male Lewis rats underwent sciatic nerve transection and subsequent epineural suture repair. The treatment group received ADSCs re-suspended in fibrin glue, while the control group received fibrin glue only. After 7, 21, 35, and 63 days, analysis involved axon count, myelin sheath thickness as well as N- and G-ratios. Additionally, muscle weight quotient (operated vs. non-operated site of the same animal) was calculated and compared between treatment and control groups. For co-detection of vital ADSCs, vessel walls, and Schwann cells, immunolabeling was performed with CM-DiI, SMA, and S-100 antibodies, respectively. RESULTS: ADSCs led to a significant increase of myelinization at day 21 (0.508 ± 0.085 µm vs. 0.381 ± 0.044 µm, P = 0.025) and day 35 (0.872 ± 0.09 µm vs. 0.495 ± 0.078 µm; P = 0.01) after surgery. Axon count was significantly increased at day 21 (420 ± 119 vs. 129 ± 63; P = 0.003) and day 63 (284 ± 137 vs. 111 ± 26; P = 0.046) after surgery. N- and G-ratios were significantly different compared with control indicating enhanced nerve regeneration due to ADSC treatment at each time point (P < 0.05). Muscle weight quotient was significantly higher in the treatment group compared with the control at day 21 (44.01% ± 6.16% vs. 35.03% ± 2.61%; P = 0.014) and day 63 (65.49% ± 2.81% vs. 58.79% ± 4.06%; P = 0.009) after surgery. Co-detection of immunolabeled cells showed vital ADSCs at the neuronal repair site and in close proximity to intraneuronal vessels indicating active participation of ADSCs in the process of nerve regeneration and associated angiogenesis. CONCLUSION: ADSCs embedded in a fibrin matrix can significantly enhance regeneration of peripheral nerve injuries after primary coaptation. © 2015 Wiley Periodicals, Inc. Microsurgery 36:491-500, 2016.

Surgical treatment of primary gynecomastia in children and adolescents.

PURPOSE: Idiopathic gynecomastia is a common diagnosis in children and adolescents. Though medical treatments reveal potentially harmful side effects, surgical interventions are performable in numerous techniques. In children and adolescents, only minimal evidence exists. This retrospective study presents our experiences with two common surgical techniques, namely subcutaneous mastectomy and combination with liposuction. PATIENTS AND METHODS: This retrospective study included all patients <18 years who underwent surgery due to idiopathic gynecomastia. Height, weight and grade of gynecomastia according to Simon's classification before surgery were reviewed in all patients' files. Additionally, duration of surgery, inpatient stay and postoperative complications were documented. Follow-up examinations were performed with assessment of scar formation, numbness and retraction of the nipple region. Furthermore, patients were asked to report on general satisfaction with surgery (satisfactory/not satisfactory) and esthetic outcome on a numeric scale (1 = good, 6 = bad). RESULTS: 37 patients underwent surgery for verified idiopathic gynecomastia. Grade of gynecomastia was I° in 13.5% (n = 5), II° in 40.5% (n = 15) and III° in 46% (n = 17) of cases. Subcutaneous mastectomy was applied in 11 patients (group I, 30%) and both subcutaneous mastectomy and liposuction in 26 patients (group II, 70.3%). Postoperative complications occurred in two patients. Long-term follow-up was performed in 32 patients after a median of 34 months (range 6-96 months). Hypertrophic scar formation was seen in one patient (3%) and nipple retraction in two patients (5%). Recurrence of gynecomastia occurred in two patients (5%). Patient rating was satisfactory in 9% of cases and esthetic outcome was received with a median of 2.0 (1-5). In comparing both surgical techniques, combination of mastectomy and liposuction revealed better results in every measure except for surgical duration (median 73 vs. 90 min). CONCLUSION: Surgical correction of gynecomastia remains a purely elective intervention. In contrast to adults, skin in children and adolescents provides high retractability. Therefore, open reduction combined with minimally invasive liposuction was proven useful.

Pulsed acoustic cellular expression (PACE) reduces capsule formation around silicone implants.

UNLABELLED: Capsular contracture remains a major complication after reconstructive or aesthetic breast augmentation. Formation of capsular fibrosis is a multifactorial process. An initial inflammatory reaction appears to be key to the development of capsular contracture. Recent studies have shown that pulsed acoustic cellular expression (PACE) has significant antiinflammatory effects. Thus, this study aimed to determine the potential of PACE to prevent or attenuate capsular contracture around silicone implants in a rodent model. For this study, 36 Lewis rats were divided into two groups, and a textured silicone implant was placed in a dorsal submuscular pocket. One group received PACE treatment, whereas the other group served as the control group and received no treatment. Follow-up evaluations were performed after 10, 35, and 100 days. Capsule thickness, collagen density, myofibroblasts, vascular density, and a semiquantitative real-time polymerase chain reaction that addressed differential gene expression were assessed. The PACE treatment significantly reduced capsule thickness on days 10, 35, and 100 compared with the control group (day 10: 632.9 ± 164.5 vs 932.6 ± 160.8, p < 0.05; day 35: 709.5 ± 175 vs 825.9 ± 313.3, p < 0.0.5; day 100: 736.3 ± 198.1 vs 1,062.3 ± 151.9, p < 0.05). This was accompanied by a significant suppression of proinflammatory genes (cluster of differentiation 68, monocyte chemotactic protein-1, CCL4) and synergistic alterations of pro- and antifibrotic proteins (transforming growth factor-beta 1, matrix metalloproteinase-2). This study showed that the PACE application significantly reduces capsular contracture around silicone implants. A decrease in capsular thickness after PACE treatment seems to be associated with a downregulation of proinflammatory genes and proteins. The study identifies PACE technology as a potential low-cost technique that is easy to use for reduction of capsular contracture after augmentation using silicone implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Bed isolation in experimental flap studies in rats: a dispensable procedure.

Review of the literature regarding rodent experimental flap models reveals fundamental differences in applied surgical procedures. Although some authors isolate the flap from its wound bed, others do not. This study was planned to investigate to what extent the insertion of a silicone sheet affects physiological wound healing in experimental flap surgery. An extended epigastric adipocutaneous flap (6 × 10 cm) was raised in 16 male Lewis rats. In the control group (group C), flaps were immediately inset without any intervention. In the experimental group (group M), a silicone sheet barrier was placed between the flap and the wound bed. Mean flap survival area and flap perfusion were evaluated. Microvessel density was visualized by immunohistochemistry, and semiquantitative real-time polymerase chain reaction addressed differential gene expression. All animals were investigated on postoperative day 5. Flap survival area and flap perfusion were found to be similar. Immunohistochemistry, however, demonstrated a significantly increased number of CD31-positive small vessels in group C. The insertion of the silicone sheet barrier (group M) was accompanied by a significantly enhanced expression of proinflammatory genes and a suppression of proangiogenic genes. Our results show that although the silicone membrane has no influence on the surgical outcome in terms of flap survival and perfusion, it does lead to significant molecular alterations in pathways involved in physiological wound healing. These alterations are artificially induced by the foreign body material and conceal the true driving forces of the healing process. As the latter might include relevant therapeutic targets to ameliorate surgical results, we regard wound bed isolation as a dispensable procedure in the study of rodent flap models.

Optimal timing of extracorporeal shock wave treatment to protect ischemic tissue.

Enhancement of flap survival through extracorporeal shock wave treatment (ESWT) is a promising new technique; however, no attempt has been made to define the optimal time point and frequency of ESWT to optimize treatment with ESWT for ischemic indications. Twenty-eight male Wistar rats were randomized into 4 groups and an oversized, random-pattern flap was raised and reattached in place in each animal. ESWT was applied 7 days before (group E7) or immediately after the surgical intervention (group E0). The third group was treated with ESWT 7 days before and additionally immediately after the operation (group E7/0). The fourth group served as a control group and did not receive any ESWT (group C). Seven days after flap harvest the results of flap survival, perfusion, microvessel density, and vascular endothelial growth factor concentrations were assessed. Flap survival was significantly increased in all ESWT groups as compared with the control group. The groups (E7 and E0) that received ESWT pre- or postoperatively showed a significant increase in flap perfusion and microvessel density. Combined pre- and postoperative ESWT application (group E0/E7) did not demonstrate a cumulative effect in any evaluation. In this study, we were be able to prove the effectiveness of ESWT in the protection of ischemic tissue flaps. This study suggests that single postoperative application is the most efficacious protocol for clinical applications of ESWT in the treatment of ischemic tissue.

Modulation of Nitric Oxide Bioavailability Attenuates Ischemia-Reperfusion Injury in Type II Diabetes.

BACKGROUND: Diabetes mellitus increases the susceptibility of free tissue transplantations to ischemia-reperfusion injury. The aim of this study was to enhance nitric oxide (NO) bioavailability through exogenous NO synthase and the substrate L-arginine to attenuate ischemia reperfusion-induced alterations in a type 2 diabetes rodent model. MATERIAL AND METHODS: Sixty-four Wistar rats were divided into 8 experimental groups. Type 2 diabetes was established over 3 months with a combination of a high-fat diet and streptozotocin. A vascular pedicle isolated rat skin flap model that underwent 3 h of ischemia was used. At 30 min before ischemia, normal saline, endothelial NOSs (eNOSs), inducible NOSs, neuronal NOSs (1 and 2 IU), and L-arginine (50 mg/kg body weight) were administered by intravenous infusion alone or in combination. Ischemia-reperfusion-induced alterations were measured 5 days after the operation. RESULTS: The three isoforms of NOS significantly increased the flap vitality rate (VR) between 20% and 28% as compared to the control group (3%). Sole L-arginine administration increased the VR to 33%. The combination of L-arginine with NOS resulted in a further increase in flap VRs (39%-50%). Best results were achieved with the combination of eNOS and L-arginine (50%). An increase in enzyme dosage led to decreased VRs in all NOS isoforms alone and even in combination with L-arginine. CONCLUSION: Modulation of NO bioavailability through the exogenous application of NOSs and L-arginine significantly attenuated ischemia-reperfusion-induced alterations in a type 2 diabetic skin flap rat model. The combination of enzyme and substrate result in the highest VRs. Higher enzyme dosage seems to be less effective. This pharmacological preconditioning could be an easy and effective interventional strategy to support the conversion of L-arginine to NO in ischemic and in type 2 diabetic conditions.

Antiseptic therapy with a polylacticacid-acetic acid matrix in burns.

Bacterial colonization and infection are still the major causes of delayed healing and graft rejection following burns and they are furthermore the basis for second and third hit sepsis. Topical treatment is necessary to reduce the incidence of burn wound infection. Silver sulphadiazine (SD-Ag) is a frequently used microbicidal agent. However, this treatment causes adverse reactions and side-effects. Additionally, in recent years multiresistant bacteria, which have not been treated sufficiently, are on the rise. On the basis of experimental data and clinical application of a polylacticacid-acetic acid matrix, we performed this study to establish the effectiveness of the antiseptic therapy with the topical application of a polylacticacid-acetic acid matrix to provide an alternative method for burn treatment, using SD-Ag as a reference. Twenty patients with IIb° or III° burns from the Plastic Surgery and Burns Unit were treated within a matched pair comparative setting. One burned area was treated with SD-Ag, the other corresponding area with the polylacticacid-acetic acid matrix. All patients underwent a necrectomy 4-5 days after the trauma. The excised burned skin was sent to our microbiological laboratory to determine the different bacteria per gram in this tissue. Despite the number of 20 patients, statistical significance was not achieved, there were tendencies to a better antiseptic effectiveness of the polylacticacid-acetic acid matrix. These results suggest that the polylacticacid-acetic acid matrix should be studied in greater depth and could be used as a valid alternative for the topical treatment of burns, as it is equivalent or even more effective than SD-Ag.

Preoperative shock wave therapy reduces ischemic necrosis in an epigastric skin flap model.

Extracorporeal shock wave therapy (ESWT) has recently been demonstrated to improve skin flap survival. In all these studies EWST was applied immediately after the surgical intervention. Thus, the purpose of this study was to determine the preoperative effect of ESWT as a noninvasive technique to precondition flap tissue in a rat epigastric skin flap model. EWST and control groups each contained 10 animals. ESWT was applied 7 days before the surgical intervention, whereas the control group received no treatment. Follow-up evaluation was performed on postoperative day 5. The mean area of flap necrosis, expressed as a percentage of the total flap area, was calculated. A significant reduction of the average flap necrosis area was observed in the ESWT group (27.2% +/- 9.6%) compared with the control group (46.1% +/- 7.9% (P < 0.05). In summary, this study indicates that preoperative ESWT may enhance skin flap survival in a rodent model.

Rodent models of diet-induced type 2 diabetes mellitus: A literature review and selection guide.

Several research teams have focused on finding the "ideal" animal model that reflects the pathophysiological changes and closely simulates the metabolic characteristics of patients with type 2 diabetes. However, the multitude of studies on this topic has resulted in large variations, making the models difficult to compare, as the measured parameters vary significantly. Additionally, selecting the appropriate animal model for a new study has become more difficult due to the increasing number of background variables. This article gives a detailed overview of the literature, covering the entire range of animal models and model characteristics, and most importantly, provides guidance for selecting the most suitable model for specific research goals in the future.

Dealing with the mass: a new approach to facilitate panniculectomy in patients with very large abdominal aprons.

BACKGROUND: Panniculectomy surgery is performed to remove a massive pannus, or abdominal apron, which frequently contributes to a number of health concerns. The resection of such a massive abdominal panniculus is technically difficult due to the weight of the tissue and the difficulty in handling it during surgery. METHODS: We performed a retrospective review on 20 morbidly obese patients (14 male, six female) who underwent a panniculectomy with a resection weight of >6 kg between November 2003 and November 2007 at our department. RESULTS: The patients' weight ranged from 90 to 240 kg, with a mean weight of 157.6 kg. The redundant pannus weighed from 6.8 to 60.0 kg. Uncomplicated healing occurred in 55% of cases. Further complications were not observed. CONCLUSIONS: The treatment of a massive panniculus requires a multitask management considering optimal conditions for the surgeon and patient. Based on our experience from 20 patients over 4 years, we are able to present our standardized and improved technique using a mechanical lift and a tumescent solution to facilitate this procedure.

Silicone Implants with Smooth Surfaces Induce Thinner but Denser Fibrotic Capsules Compared to Those with Textured Surfaces in a Rodent Model.

PURPOSE: Capsular contracture is the most frequent long-term complication after implant-based breast reconstruction or augmentation. The aim of this study was to evaluate the impact of implant surface properties on fibrotic capsule formation in an animal model. MATERIALS AND METHODS: Twenty-four rats received 1 scaled down silicone implant each; 12 of the rats received implants with textured surfaces, and the other 12 received implants with smooth surfaces. After 60 and 120 days, rats in each group underwent 7-Tesla Magnetic Resonance Imaging (MRI) and high-resolution ultrasound (HR-US), and specimens of the capsules were acquired and used to measure capsule thickness through histology, collagen density through picro sirius red staining, and analyses of expression of pro-fibrotic and inflammatory genes (Collagen1-4, TGFb1, TGFb3, Smad3, IL4, IL10, IL13, CD68) through qRT-PCR. Furthermore, MRI data were processed to obtain capsule volume and implant surface area. RESULTS: On day 60, histology and HR-US showed that fibrotic capsules were significantly thicker in the textured implant group with respect to the smooth implant group (p<0.05). However, this difference did not persist on day 120 (p=0.56). Capsule thickness decreased significantly over the study period in both smooth and textured implant groups (p<0.05). Thickness measurements were substantiated by MRI analysis and volumes changed accordingly. Implant surface area did not vary between study dates, but it was different between implant types. On day 60, the density of collagen in the fibrotic capsules was significantly lower in the textured implant group with respect to the smooth group (p<0.05), but again this difference did not persist on day 120 (p=0.67). Collagen 1 and CD68 were respectively over- and under expressed in the textured implant group on day 60. Significant differences in the expression of other genes were not observed. CONCLUSION: Silicone implants with textured surfaces led to temporarily thicker but less dense fibrotic capsules compared with smooth surfaces. 7-Tesla MRI and HR-US are capable for non-invasive in-vivo assessment of capsular fibrosis in an animal model and can provide unique insights into the fibrotic process by 3D reconstruction and surface area measurement.

Multiple extracorporeal shock wave therapy degrades capsular fibrosis after insertion of silicone implants.

Capsular fibrosis is the most frequent long-term complication after insertion of silicone devices. Today, mainly direct immunostimulation and subclinical infection are held responsible for inducing and maintaining inflammatory reactions, which lead to overwhelming extracellular matrix formation. Extracorporeal shock waves (ESWs) are capable of inhibiting inflammatory processes and revealing antibacterial capacity. In our previous study, we observed decelerated capsule development after application of a single shock wave immediately after surgery. The purpose of this study was to evaluate the effects of multiple ESWT after insertion of silicone implants in the same rodent model. Therefore, silicone prostheses were inserted into a submuscular pocket in 12 additional male Lewis rats, and shock waves were administered over a 14-d interval. At 35 d (n = 6) and 100 d (n = 6) after insertion, silicone implants and surrounding capsule tissue were removed and prepared for histologic and immunohistochemical analysis, as well as polymerase chain reaction (Ccl2, CD68, transforming growth factor ß1, matrix metalloproteinase 2). Compared with the control group, multiple ESWT had no effect on day 35, but resulted in a significantly thinner capsule on day 100 (825.8 ± 313.2 vs. 813.3 ± 47.9, p = 0.759, and 1062.3 ± 151.9 vs. 495.4 ± 220.4, p < 0.001, respectively). The capsule was even thinner than after a single shock wave application, which had been found to result in thinner capsules at every time point in our previous study. This active degradation of the fibrous envelope caused by multiple ESWs was accompanied by synergistic alterations in pro- and anti-fibrotic proteins (transforming growth factor ß1 and matrix metalloproteinase 2, respectively). In conclusion, after insertion of silicone devices, single ESWT is capable of decelerating capsule formation in contrast to multiple ESWT, which degrades fibrotic tissue. These findings seem to be associated with inhibition of inflammation and beneficial effects on pro- and anti-fibrotic proteins.

Extracorporeal shock wave treatment protects skin flaps against ischemia-reperfusion injury.

Advances in the treatment of ischemia-reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. Using an extended inferior epigastric artery skin flap as a flap ischemia-reperfusion injury (IRI) model, we examined the capability of extracorporeal shock wave treatment (ESWT) to protect tissue against IRI in a rat flap model. Twenty-four rats were used and randomly divided into three groups (n=8 for each group). Group I was the sham group and did not undergo ischemic insult; rather, the flap was raised and immediately sutured back (non-ischemic control group). Group II (ischemia control) and Group III (ESWT) underwent 3h of ischemic insult. During reperfusion Group III was treated with ESWT and Group II was left untreated. Histological evaluation was made to investigate treatment induced tissue alterations. Survival areas were assessed at 5d postoperatively. Skin flap survival and perfusion improved significantly in the ischemic animals following ESWT (p<0.001, respectively). The tissue protecting effect of ESWT resulted in flap survival areas and perfusion data equal to non-ischemic, sham operated flaps. In line with the observation of better flap perfusion, tissue from ESWT-treated animals (Group III) revealed a significantly increased frequency of CD31-positive vessels compared to both the ischemic (Group II; p=0.003) and the non-ischemic, sham operated control (Group I; p<0.005) and an enhanced expression of pro-angiogenic genes. This was accompanied by a mild suppression of pro-inflammatory genes. Our study suggests that ESWT improves flap survival in IRI by promoting angiogenesis and inhibiting tissue inflammation. The study identifies ESWT as a low-cost and easy to use technique for surgical techniques that aim at reducing ischemia-reperfusion-induced tissue injury.

Adipose derived stem cells protect skin flaps against ischemia-reperfusion injury.

BACKGROUND: Advances in the treatment of ischemia- reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. We examined the capability of adipose derived stem cells (ADSCs) to protect tissue against IRI using an extended inferior epigastric artery skin flap as a flap ischemia- reperfusion injury (IRI) model. METHODS: ADSCs were isolated from Lewis rats and cultured in vitro. Twenty- four rats were randomly divided into three groups. Group I was the sham group and did not undergo ischemic insult; rather, the flap was raised and immediately sutured back (non-ischemic control group). Group II (ischemia control) and group III (ADSCs treatment) underwent 3 h of ischemic insult. During reperfusion group III was treated by intravenous application of ADSCs and group II was left untreated. Five days postoperatively, flap survival and perfusion were assessed. Microvessel density was visualized by immunohistochemistry and semi- quantitative real-time polymerase chain reaction addressed differential gene expression. RESULTS: Treatment with ADSCs significantly increased flap survival (p<0.001) and flap perfusion (p<0.001) when compared to the control group II. Microvessel- density in ADSCs treated group was not significantly increased in any group. No significant differences showed the comparison of the experimental group III and the sham operated control group I. ADSCs treatment (Group III) was accompanied by a significantly enhanced expression of pro-angiogenic and pro-inflammatory genes. CONCLUSION: Overall, our study demonstrates that ADSCs treatment significantly enhances skin flap survival in the aftermath of ischemia to an extent that almost equals surgical results without ischemia. This effect is accompanied with a pronounced and significant angiogenic response and an improved blood perfusion.

Preoperative shock wave treatment enhances ischemic tissue survival, blood flow and angiogenesis in a rat skin flap model.

INTRODUCTION: Extracorporeal shock wave treatment (ESWT) has recently been shown to enhance skin flap survival. However, the bio-mechanisms operating during preoperative ESWT remain unclear. The aim of our study was to investigate whether preoperative ESWT can improve blood flow in ischemic skin flaps and to elucidate its possible mechanisms. METHODS: 14 male-rats were randomized into two groups and an oversized ventral random-pattern flap was raised. Experimental group received extracorporeal shock-wave treatment (ESWT) with an energy of 500 mJ/mm(2) seven days prior to total flap elevation, while control group received no treatment prior to total flap elevation. Seven days postoperatively, surviving flap area, perfused flap area, microvessel density and VEGF concentration were measured. RESULTS: Surviving flap area (59.43 ± 14.72 % to 42.71 ± 10.75 %, p = 0.026), perfused flap area (62.00 ± 8.58 % to 45.14 ± 10.50 %, p = 0.007), microvessel density (18.13 ± 5.11 to 11.09 ± 1.12, p = 0.016) and VEGF to total protein ratio (0.2107 ± 0.0935 to 0.0123 ± 0.0069, p = 0.008) were significantly elevated in the ESWT group. CONCLUSION: Preoperative ESWT can improve skin flap survival through enhanced topical blood perfusion and neovascularization via elevation of angio-active factors.

CASE REPORT Febrile Ulceronecrotic Mucha-Habermann Disease.

OBJECTIVE: Case report and review of the current literature about febrile ulceronecrotic Mucha-Habermann disease (FUMHD). METHODS: Review of our patient's medical records and of the current literature. RESULTS: The FUMHD is a rare and potentially lethal type of pityriasis lichenoides et varioliformis acuta. It is characterized by the sudden onset of ulceronecrotic skin lesions associated with high fever and systemic symptoms. Because of a high case-fatality rate it requires quick and decisive action. Only 40 cases of this severe form of the disease have been reported in the literature to date. We present the case of a 30-year-old male patient with severe FUMHD who was successfully treated in our burn intensive care unit after failed treatment at a dermatological hospital. The patient was treated with topical antiseptics, moisturizers, and artificial skin substitutes, as well as systemic immunosuppressive therapy (glucocorticoids) with which we were able to control the disease activity so that healing of the patient's skin lesions could be achieved. CONCLUSION: Patients with FUMHD should be treated in a specialized center for severely burned patients. Only such centers can provide the structural and logistical capacities necessary for the treatment of such extensive superficial wounds.

Arteriovenous loops in microsurgical free tissue transfer in reconstruction of central sternal defects.

OBJECTIVE: In some patients with chest wall defects, free tissue transfer is indicated. Complications arise if multiple operations have left the trunk devoid of recipient vessels. In such patients, an arteriovenous loop between the cephalic vein and the thoracoacromial artery can be used. METHODS: A review of all our patients who underwent chest wall reconstruction with a cephalic vein-thoracoacromial artery loop between 2000 and 2009 was performed (n = 29, 19 women and 10 men). The mean age was 64.9 years. Underlying causes were sternal osteomyelitis (n = 20), tumor (n = 4), and osteoradionecrosis (n = 5). All patients were in American Society of Anesthesiologists classes III and IV. Flap selection, intraoperative and postoperative complications, operative time, time of ventilatory support, mean hospital stay, and midterm survival were recorded. RESULTS: Twenty-five patients received a tensor fascia lata flap, 2 a vertical rectus myocutaneuos flap, and 2 a deep inferior epigastric perforator flap. Mean duration of surgery was 6.8 hours (4.7-10.5 hours). Two transplanted tissue flaps died and/or had to be removed and 4 were revised successfully. Seven patients had wound complications such as infection or prolonged wound healing. Mean time for ventilator support was 93.6 hours (4-463 hours). The median intensive care unit time was 11 days and the overall hospital stay 27.4 days (11-102 days). One-year survival in the whole group was 69.8%. CONCLUSIONS: The concept of arteriovenous loops allows creation of neovessels at the recipient site and has proven to be a superb tool to facilitate free tissue transfer or to provide an exit strategy in situations with unexpected vascular problems at the recipient site.