Abstract Background Damage control is essential in first aid of burn lesions. The aim of the present study was to investigate whether systemic erythropoietin (EPO) administration could prevent secondary burn progression in an experimental model. Methods The burn comb model creates four rectangular burn surfaces intercalated by three unburned zones prone to progression. Twenty-one Wistar rats were randomized to a control group or to receive intraperitoneal EPO (500 units per kg) once a day for 5 days starting 45 min (EPO45min) or 6 h (EPO6h) after burn injury. Histological analyses assessing burn depth, inflammation and neoangiogenesis, planimetric evaluation of burn progression, and laser Doppler flowmetry to assess perfusion were performed after 1, 4 and 7 days. Final scarring time and contracture rate were assessed once a week. Results Burn progression was decreased significantly with EPO45min but not EPO6h; progression of burn depth stopped in the intermediate dermis (mean(s.e.m.) burn depth score 3·3(0·6) for EPO45min versus 4·7(0·3) and 5·0(0·0) for EPO6h and control respectively on day 7; P = 0·026) and the surface extension was significantly reduced (45(8), 65(4) and 78(4) respectively on day 7; P = 0·017). This was paralleled by faster re-establishment of perfusion with EPO45min (114(5) per cent on day 4 versus 85(6) and 91(3) per cent for EPO6h and control respectively; P = 0·096). The reduction in progression resulted in a decreased healing time (7·3(0·7) weeks for EPO45min versus 11·5(1·0) and 10·8(0·5) weeks for EPO6h and control; P = 0·020) and contracture rate (P = 0·024). Conclusion Early EPO prevented burn progression, mainly by improved vascular perfusion.
Insufficient vascularization is considered to be one of the main factors limiting the clinical success of tissue-engineered constructs. In order to evaluate new strategies that aim at improving vascularization, reliable methods are required to make the in-growth of new blood vessels into bio-artificial scaffolds visible and quantify the results. Over the past couple of years, our group has introduced a full skin defect model that enables the direct visualization of blood vessels by transillumination and provides the possibility of quantification through digital segmentation. In this model, one surgically creates full skin defects in the back of mice and replaces them with the material tested. Molecules or cells of interest can also be incorporated in such materials to study their potential effect. After an observation time of one's own choice, materials are explanted for evaluation. Bilateral wounds provide the possibility of making internal comparisons that minimize artifacts among individuals as well as of decreasing the number of animals needed for the study. In comparison to other approaches, our method offers a simple, reliable and cost effective analysis. We have implemented this model as a routine tool to perform high-resolution screening when testing vascularization of different biomaterials and bio-activation approaches.
The breast is essential to a woman's physical integrity. There are numerous techniques for breast reconstruction, so that the needs and limitations of each patient can be respected. The individual preferences of the patient play an important role in the decision of silicone implants vs. autologous tissue, size, and shape of the breast as well as the timing of the surgery. The only reasons not to perform a reconstruction are a locally incompletely removed tumor or the explicit wish of the patient against reconstruction. The costs for reconstruction are covered by the health insurance for all procedures, including symmetrizing the opposite breast, nipple reconstruction and autologous fat grafting.Individuelle Bedürfnisse der Patientin bei der Brustrekonstruktion – gibt es Grenzen für die Plastische Chirurgie?Die Brust ist das Sinnbild für Weiblichkeit und kann essenziell sein für die körperliche Integrität einer Frau. Es gibt zahlreiche Techniken zur Brustrekonstruktion, sodass die Bedürfnisse und Limitationen jeder Patientin berücksichtigt werden können. Bezüglich der Entscheidung Silikonimplantate vs. Eigengewebe, Grösse und Form der Brust sowie Timing spielen die individuellen Präferenzen der Patientin eine wichtige Rolle. Die einzigen Gründe, auf eine Rekonstruktion zu verzichten, ist ein lokal unvollständig entfernter Tumor oder der entsprechende Wunsch der Patientin. Die Kosten für die Rekonstruktion werden von der Krankenkasse für alle Verfahren übernommen, auch für die Anpassung der Gegenseite, die Mamillenrekonstruktion und eventuelle Fettgewebetransfers. Schlüsselwörter: Brustkrebs, autologe Brustrekonstruktion, implantatbasierte Brustrekonstruktion, Mamillenrekonstruktion, autologer Fettgewebstransfer.Les besoins individuels de la patiente dans la reconstruction mammaire – quelles sont les limites de la chirurgie plastique?Résumé: Le sein est essentiel à l‘intégrité physique de la femme. Il existe de nombreuses techniques de reconstruction mammaire qui permettent de prendre en compte les besoins et les limites de chaque patiente. Les préférences individuelles de la patiente jouent un rôle important dans le choix des implants en silicone ou des tissus autologues, de la taille et de la forme du sein ainsi que du moment des interventions chirurgicales. Les seules raisons de ne pas effectuer une reconstruction sont une tumeur localement incomplètement enlevée ou le souhait explicite de la patiente. Les coûts de la reconstruction sont couverts par l‘assurance maladie pour toutes les interventions, y compris la symétrisation du sein opposé, la reconstruction du mamelon et la greffe de graisse autologue. Mots-clés: Cancer du sein, reconstruction mammaire autologue, reconstruction mammaire par implants, reconstruction du mamelon, transfer du tissue adipeux autologue.
Erythropoetin (EPO) ist ein körpereigenes Hormon, welches durch Fibroblasten des Nierenparenchyms produziert wird und die Ausdifferenzierung der Erythrozyten im Knochenmark steuert. Seit 30 Jahren wird es therapeutisch bei Anämien der terminalen Niereninsuffizienz, bei tumorinduzierten Anämien und vor der Eigenblutspende eingesetzt. Mittlerweile konnte in einer großen Anzahl von Arbeiten demonstriert werden, dass EPO zudem eine Schlüsselrolle bei der Reaktion auf akute und chronische Gewebeschäden einnimmt. Es konnte gezeigt werden, dass EPO in einer Vielzahl von Geweben in der Akutphase nach Trauma synthetisiert wird. Es hemmt die initiale Entzündungsreaktion und die Apoptose, stimuliert die Stammzellrekrutierung und die Ausschüttung verschiedener Wachstumsfaktoren sowie die Angiogenese und die Re-Epithelialisierung. Unerwünschte Wirkungen von EPO sind u. a. Erhöhung der Thromboseneigung und des Blutdrucks sowie kürzere Überlebenszeiten von mit EPO behandelten Patienten mit Tumoranämien. Wissenschaftlich untersuchte Einsatzbereiche von EPO in dem Gebiete der plastischen Chirurgie sind: Lappenplastiken (lokale und freie), die Regeneration peripherer Nerven sowie die Wundheilungsförderung in thermischen Verletzungen und in chronischen Wunden. Aktuell ist die Evidenzlage insbesondere für den konkreten klinischen Einsatz aufgrund mangelnder Ergebnisse von GCP (good clinical practice) -gerechten klinischen Studien jedoch ungenügend. Die Durchführung weiterer wissenschaftlich und formal anspruchsvoller Studien ist daher notwendig.
In Brief Objective: The objective of this study was to analyze whether erythropoietin (EPO) protects from necrosis of critically perfused musculocutaneous tissue and the mechanisms by which this protection is achieved. Background: EPO is the regulator of erythropoiesis and is used to treat patients with anemia of different causes. Recent studies suggest that EPO has also other tissue-protective effects, irrespective of its erythropoietic properties. Material and Methods: C57BL/6-mice were treated with 3 doses of EPO at 500 IU/kg intraperitoneally. EPO was given either before (preconditioning, n = 7), before and after (overlapping treatment, n = 7), or after (treatment, n = 7) surgery. Animals receiving only saline served as controls (CON). Acute persistent ischemia was induced by elevating a randomly perfused flap in the back of the animals. This critically perfused tissue demonstrates an initial microvascular failure of ∼40%, resulting in ∼50% tissue necrosis if kept untreated. Repetitive fluorescence microscopy was performed over 10 days, assessing angiogenesis, functional capillary density, inflammatory leukocyte-endothelial cell interaction, apoptotic cell death, and tissue necrosis. Additional molecular tissue analyses included the determination of inducible nitric oxide synthase, erythropoietin receptor (EPO-R), and vascular endothelial growth factor (VEGF). Results: EPO preconditioning did not affect hematocrit and EPO-R expression, but increased inducible nitric oxide synthase in the critically perfused tissue. This correlated with a significant arteriolar dilation, which resulted in a maintained functional capillary density (CON: 0 ± 0 cm/cm2; preconditioning: 37 ± 21 cm/cm2; overlapping treatment: 72 ± 26 cm/cm2; P < 0.05). EPO pretreatment further significantly reduced microvascular leukocyte adhesion and apoptotic cell death. Moreover, EPO pretreatment induced an early VEGF upregulation, which resulted in new capillary network formation (CON: 0 ± 0 cm/cm2; preconditioning: 40 ± 3 cm/cm2; overlapping treatment: 33 ± 3 cm/cm2; P < 0.05). Accordingly, EPO pretreatment significantly reduced tissue necrosis (CON: 48% ± 2%; preconditioning: 26% ± 3%; overlapping treatment: 20% ± 3%; P < 0.05). Of interest, EPO treatment was only able to alleviate ischemia-induced inflammation but could not improve microvascular perfusion and tissue survival. Conclusions: EPO pretreatment improves survival of critically perfused tissue by nitric oxide -mediated arteriolar dilation, protection of capillary perfusion, and VEGF-initiated new blood vessel formation. Preconditioning with erythropoietin improves survival of critically perfused musculocutaneous flap tissue by maintaining nutritive perfusion and inducing angiogenesis. The protection results from a nitric oxide-dependent arteriolar dilation and an upregulation of vascular endothelial growth factor.
