Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving microvascular perfusion.

Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and necrosis. The objective of this experimental study was to analyze, whether the gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal skinfold chamber containing ischemic musculocutaneous tissue were allocated to four groups: 1) ghrelin; 2) N(ω)-nitro-l-arginine methyl ester (l-NAME); 3) ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis, and tissue survival were assessed by fluorescence microscopy. Inducible and endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth factor (VEGF), as well as nuclear factor κB (NF-κB) were assessed by Western blot analysis. Ghrelin-treated animals showed an increased expression of iNOS and eNOS in critically perfused tissue compared with controls. This was associated with arteriolar dilation, increased arteriolar perfusion, and a sustained functional capillary density. Ghrelin further upregulated NF-κB and VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte-endothelial cell interactions, apoptosis, and overall tissue necrosis (P < 0.05 vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti-inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin-induced tissue protection by abrogating the arteriolar dilation, the improved capillary perfusion, and the increased tissue survival. Ghrelin prevents critically perfused tissue from ischemic necrosis. Tissue protection is the result of a nitric oxide synthase-mediated improvement of the microcirculation but not due to induction of angiogenesis or attenuation of inflammation. This might represent a promising, noninvasive, and clinically applicable approach to protect musculocutaneous tissue from ischemia.

Erythropoietin in the prevention of experimental burn progression.

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.

N-acetylcysteine attenuates leukocytic inflammation and microvascular perfusion failure in critically ischemic random pattern flaps.

INTRODUCTION: Microcirculatory dysfunction causes ischemia resulting in tissue necrosis. N-acetylcysteine (NAC) has been shown capable of protecting tissue from ischemic necrosis. However, the mechanism of action of NAC is yet not fully understood. OBJECTIVE: Herein, we studied whether NAC is capable of attenuating microvascular perfusion failure in critically ischemic musculo-cutaneous tissue. MATERIAL AND METHODS: A laterally based skin flap was elevated in the dorsum of C57BL/6 mice and fixed into a dorsal skinfold chamber. Arteriolar perfusion, functional capillary density, leukocytic inflammation, apoptotic cell death, and non-perfused tissue area were repetitively analyzed over 10 days by intravital fluorescence microscopy. Treatment with either 100mg/kg NAC or saline (control) was started 30 min before surgery and was continued until day 10 after flap elevation. RESULTS: Surgery induced leukocytic inflammation, microvascular perfusion failure, apoptosis, and tissue perfusion failure. NAC was capable of significantly attenuating the area of non-perfused tissue. This was associated by a marked arteriolar dilation and an increased capillary perfusion. NAC further reduced the ischemia-associated leukocytic response and significantly attenuated apoptotic cell death in all areas of the flap. CONCLUSION: NAC is effective to attenuate leukocytic inflammation and microvascular perfusion failure in critically ischemic tissue. Thus, NAC treatment may represent a promising approach to improve the outcome of ischemically endangered flap tissue.

[Training in aesthetic surgery at a university clinic - the "Munich model"]. / Weiterbildung in der ästhetischen Chirurgie an einer Universitätsklinik - Das "Münchner Modell"

BACKGROUND: Aesthetic surgery is regarded as one of the 4 pillars of plastic surgery. To assure safety in this field of surgery, a structured and well guided surgical training is indispensable. However, during the specialist training for plastic and aesthetic surgery, plastic aesthetic interventions are often carried out in low numbers only. Objective of the present study was the development, implementation and evaluation of a new training concept in aesthetic surgery. PATIENTS: Over a period of 2 years, 304 aesthetic operations were performed in the fields of body contouring, breast surgery and facial surgery as an "educational surgery". Educational surgeries were performed by resident surgeons under the guidance of experienced specialists and under favourable financial conditions. As indicator for safety of the interventions, the incidence of complications was recorded and assessed. RESULTS: Out of a total of 304 operations included in the study 47.7% were performed as an educational surgery. In the fields of body contouring and breast surgery, the majority of interventions (51.3% and, respectively, 53%) were carried out as educational surgeries. In aesthetic surgeries of the face only 28.4% were educational surgeries. In 4.9% of all cases complications occurred. The incidences of complications were approximately the same in the educational surgeries (5.5%) and in the surgeries carried out by experienced specialists (4.4%), showing no significant difference. CONCLUSION: The presented training concept aims at ensuring high quality in patient care by structure and quality of surgical training. Our data give evidence that a structured training of residents in the field of aesthetic surgery is possible without loss in quality. We expect that -sufficient surgical education and the associated quality will consequently contribute to keep aesthetic surgeries a domain of plastic surgery and to prevent these procedures from being taken over by other surgical disciplines.

[Erythropoietin in plastic surgery]. / Erythropoetin in der Plastischen Chirurgie.

EPO is an autologous hormone, which is known to regulate erythropoiesis. For 30 years it has been used for the therapy of diverse forms of anaemia, such as renal anaemia, tumour-related anaemias, etc. Meanwhile, a multitude of scientific publications were able to demonstrate its pro-regenerative effects after trauma. These include short-term effects such as the inhibition of the "primary injury response" or apoptosis, and mid- and long-term effects for example the stimulation of stem cell recruitment, growth factor production, angiogenesis and re-epithelialisation. Known adverse reactions are increases of thromboembolic events and blood pressure, as well as a higher mortality in patients with tumour anaemias treated with EPO. Scientific investigations of EPO in the field of plastic surgery included: free and local flaps, nerve regeneration, wound healing enhancement after dermal thermal injuries and in chronic wounds.Acute evidence for the clinical use of EPO in the field of plastic surgery is still not satisfactory, due to the insufficient number of Good Clinical Practice (GCP)-conform clinical trials. Thus, the initiation of more scientifically sound trials is indicated.