First aid in burn injuries with counterintuitive warm water improves outcome

Objective: Cooling is considered a panacea in burn injury. However, burn injuries are characterized by an ischemic zone prone to progression, a phenomenon that can substantially increase morbidity. Cold-induced vasoconstriction potentially aggravates ischemia and promotes progression. Therefore we compared the effect of warm (37°C) and cold (17°C) water on burn progression. Methods: The comb burn model creates 4 rectangular burned surfaces separated by 3 unburned interspaces that become necrotic if untreated. After heating in boiling water the template was applied for 60 seconds on 24 Wistar rats randomized into 3 groups: no treatment (CON); treatment for 20 minutes with cold water (17°C: CW) or warm water (37°C: WW). Burn progression in surface (planimetry) and Departmenth (histology), as well as microcirculatory perfusion (laser Doppler flowmetry) were assessed after 1h, as well as 1, 4, and 7 days. Results: Both CW and WW delayed burn progression without reducing the final burn Departmenth (deep dermis). In contrast, only WW but not CW increased dermal perfusion (81 ± 2% (WW) vs. 62 ± 2% (CW) and 63 ± 1% (CON), p< 0·05) already 1 hour after burn induction. The difference observed after one hour led to a complete flow recovery during the observation period and translated into increased interspace survival, respectively less necrosis with WW(65 ± 4% vs. 81 + 4% (CW) and 91 ± 2% (CON), p< 0·05) after 7 days. Conclusions: Application of warm water significantly improved dermal perfusion, increased interspace survival, and delayed burn progression.However it didn't alter the ultimate burn Departmenth of the actually burned area. Therefore, warm water can create a therapeutic window for targeted nonsurgical treatment of burn progression

Neue Behandlungsstrategien zur Verringerung der Brandwundenprogression

Background: After a burn injury certain superficial partial-thickness burn wounds spontaneously progress into deep partial-thickness or full-thickness burn wounds. This poorly understood phenomenon is called burn wound progression. The aim of this study was to investigate whether treatment strategies using warm water (preservation of microcirculation) on the one side and erythropoietin (EPO) (molecule with anti-inflammatory, anti-apoptotic, vasodilatory and neoangiogenic properties) can prevent, delay and/or reduce secondary burn wound progression in a rat model.Methods: We used a burn comb model in 63 rats, creating eight rectangular contact burns (2x1 cm each) intercalated by unburned zones (2x0.5 cm) prone to burn wound progression. In a first experimental set we treated burn wounds with locally applied warm (37°C) or cold (17°C) water for 20 minutes.In a second experimental set, animals were treated systemically with EPO at two different dosages of 500 and 2,500 IU/kg bodyweight (bw) and initiated at 2 different time-points (45 minutes vs. 6 hours after burn injury). Evaluation of microcirculatory perfusion, interspace necrosis and burn depth was performed using respectively laser Doppler flowmetry, planimetry and histology. For statistical analysis the two-way ANOVA-test followed by an adequate post-hoc test (Bonferroni) were used. Results: In untreated control animals a conversion from superficial to full-thickness burns was observed within 24 hours. Warm and cold water treatment significantly delayed burn depth progression, nevertheless after 4 days, burn depth was similar in all three groups. Warm water significantly reduced interspace necrosis compared to untreated controls and cold water with a significantly improved perfusion in the warm water group. Surface extension and particularly burn depth progression were significantly decreased by EPO only if administered at a dosage of 500 IU/kg bw and initiated 45 minutes after burn injury. EPO administration was associated with an early hyperperfusion resulting from an increase in inducible nitric oxide synthase (iNOS) and a late angiogenic response indicated by increased microvascular density.Conclusion: First aid treatment with warm water prevents extension of the burn on the surface and delays burn depth progression, thereby creating a "therapeutic window" of approximately 4-6 hours after burn injury. This window might be used for systemic use of EPO which prevents burn progression both at the surface and into the depth if first administered 45 minutes after burn induction at a dosage of 500 IU/kg bw.Einleitung: Bei Verbrennungsverletzungen entsteht eine irreversibel geschädigte zentrale Kernzone, die von einer Stasezone umgeben ist. Die Rekrutierung dieser ischämischen Stasezone zum irreversibel geschädigten Nekroseareal hin wird Verbrennungsprogression (Nachbrennen) genannt. Ziel unserer Arbeit war es, in einem Rattenmodell zu untersuchen, ob Behandlungs-Schemata mit warmem Wasser (erhaltene Mikrozirkulation) auf der einen Seite und Erythropoetin (EPO) (anti-inflammatorische, anti-apoptotische, vasodilatatorische und neo-angiogenetische Eigenschaften) auf der anderen Seite, dieses Nachbrennen verhindern, verzögern und/oder reduzieren können.Methode: Mittels Metallstempel ("burn comb model") wurden 63 Ratten je acht 2x1 cm große Kontaktverbrennungen zugefügt, getrennt durch unversehrte Zwischenräume von 2x0,5 cm. In einem ersten Versuch wurde direkt nach der Verbrennung für 20 Minuten lokal gekühlt (17°C) oder mit 37°C warmen Wasser behandelt, mit der Hypothese, dass Wärmeapplikation die Zirkulation verbessert und die Stasezone gerettet werden kann. In einer zweiten Versuchsreihe wurde systemisch mit EPO in zwei verschiedenen Dosierungen (500 vs. 2.500 IE/kg Körpergewicht (KG)) und Verabreichungszeitpunkten (45 Minuten vs. 6 Stunden nach Verbrennungsverletzung) behandelt. Die Messungen der Tiefe der Verbrennung, der Nekrose der Zwischenräume und der mikrozirkulären Perfusion wurden anhand von Histologie, Planimetrie respektive Laser-Doppler-Perfusionsmessung durchgeführt. Die statistische Analyse erfolgte mit dem 2-Weg ANOVA-Test gefolgt vom geeigneten Post-hoc-Test (Bonferroni).Ergebnisse: Unbehandelt kam es innerhalb von 24 Stunden zur Verbrennungsprogression von oberflächlichen zu tiefen Brandwunden. Die Kälte- und Wärmeapplikation verzögerten dies, ohne jedoch die endgültige Tiefenausdehnung zu beeinflussen. Die Applikation von Wärme hingegen reduzierte die oberflächliche Ausdehnung signifikant mit einer signifikant verbesserten Perfusion in der Stasezone. Ausschließlich die frühzeitige (45 Minuten nach Verbrennung) Verabreichung von EPO 500 IE/kg KG verringerte die Verbrennungsausbreitung in Oberfläche und Tiefe signifikant. Dies wurde auf einen geringeren Perfusionsausfall bzw. raschere Normalisierung der Perfusion innerhalb der ersten 7 Tagen nach Verbrennung, was primär durch eine Expression der induzierbaren Stickstoff-Monoxid-Synthase (iNOS) zu erklären ist, zurückgeführt. Schlussfolgerung: Eine Notfallbehandlung mit warmem Wasser verhindert die oberflächliche Ausbreitung der Brandwunde und verzögert die Progression in die Tiefe. Dadurch wird ein "therapeutisches Fenster" von ca. 4-6 Stunden eröffnet. Dieses kann für die systemische Administration von EPO genutzt werden, welches die Brandwundenprogression an der Oberfläche und in die Tiefe verhindert, sofern es nach 45 Minuten in einer Dosierung von 500 IE/kg KG verabreicht wird

Local shockwave-application prevents flap necrosis

Objective: Local shockwave-application (SW) has shown to improve healing of various tissues and decrease necrosis of flaps. Though, there is no data about the optimal time-point of SW-application with regard to induction of ischemia (i.e. flap elevation) and subsequent effect on flap survival. Therefore we compared 2 shock-wave protocols in a model of persistent ischemia and investigated underlying mechanisms. Methods: 18 C57BL/6-mice equipped with a skinfold chamber containing a musculocutaneous flap were assigned to 3 experimental groups: 1. One session of 500 SWimpulses at 0·15 mJ/mm2 applied 24 hrs before (preconditioning) or 2. Applied 30 min after flap elevation (treatment). 3. Untreated flaps (control). Tissue necrosis,microhemodynamics, inflammation, apoptosis and angiogenesis were assessed by intravital epi-fluorescence microscopy over 10 days. Results: SW significantly reduced flap necrosis independent from the application time-point (preconditioning: 29 ± 7%; treatment: 25 ± 7% vs. control: 47 ± 2%; d10, p<0·05). This was associated with an early increase of functional capillary density (preconditioning: 236 ± 39 cm/cm2; treatment: 211 ± 33 cm/cm2 vs. control: 141 ± 7 cm/cm2; day1, p<0·05). Arteriolar diameter, red blood cell velocity and blood flow were comparable between the 3 experimental groups. SW-application significantly decreased the ischemiainduced inflammatory response (apoptotic cell death and leukocyte-endothelial interaction: (p<0·05)). Sprouts indicating angiogenesis were observed from day 7 only after SW-application. Conclusions: SW protects ischemically challenged musculocutaneous tissue. Interestingly, postoperative SW-application is as efficient as preoperative SWapplication. The protective effect induced by mechanical stress might be based on an early recruitment of ''sleeping capillaries'' maintaining nutritive perfusion and an anti-inflammatory effect within the ischemically jeopardized tissue. SWapplication provides a non-invasive alternative to local thermic and systemic pre-treatment of endangered tissues

Improved dynamic response assessment for intra-articular injected iron oxide nanoparticles

The emerging importance of nanoparticle technology, including iron oxide nanoparticles for monitoring development, progression, and treatment of inflammatory diseases such as arthritis, drives development of imaging techniques. Studies require an imaging protocol that is sensitive and quantifiable for the detection of iron oxide over a wide range of concentrations. Conventional signal loss measurements of iron oxide nanoparticle containing tissues saturate at medium concentrations and show a nonlinear/nonproportional intensity to concentration profile due to the competing effects of T1 and T2 relaxation. A concentration calibration phantom and an in vivo study of intra-articular injection in a rat knee of known concentrations of iron oxide were assessed using the difference-ultrashort echo time sequence giving a positive, quantifiable, unambiguous iron signal and monotonic, increasing concentration response over a wide concentration range in the phantom with limited susceptibility artifacts and high contrast in vivo to all other tissues. This improved dynamic response to concentration opens possibilities for quantification due to its linear nature at physiologically relevant concentrations

Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro.

Background: Platelet preparations for tissue healing are usually preactivated before application to deliver concentrated growth factors. In this study, the authors investigated the differences between nonactivated and thrombin-activated platelets in wound healing.Methods: The healing effects (i.e., wound closure, myofibroblast formation, and angiogenesis) of nonactivated and thrombin-activated platelets were compared in experimental wounds in diabetic (db/db) animals. In vitro, fibroblast phenotype and function were tested in response to platelets and activated platelets. No treatment served as a negative control.Results: Wounds treated with platelets reached 90 percent closure after 15 days, faster than activated platelets (26 days), and with higher levels of myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced twofold higher myofibroblast differentiation and contraction compared with activated platelets.Conclusions: Platelets stimulate wound healing more efficiently compared with activated platelets by enhancing fibroblast differentiation and contractile function. Similar levels of growth factors may induce different biological effects when delivered "on demand" rather than in an initial bolus. (Plast. Reconstr. Surg. 129: 46e, 2012.

Embolisation hémostatique des hématomes spontanés musculaires abdomino-pelviens.

Objectifs: Etudier les résultats techniques et cliniques de l'embolisation des hématomes musculaires spontanés de l'abdomen . Caractériser les hématomes ayant étéembolisés au CT et définir les éventuels critères cliniques et anatomiques pour une embolisation . Etudier la relation entre les hématomes embolisés et lesanticoagulants.Matériels et méthodes: Etude rétrospective des patients ayant bénéficié d'une embolisation pour un hématome musculaire abdominopelvien spontané entre 2005 et 2010. Sont analysésles données cliniques (anticaogulants, retentissement hémodynamqiue), les données scanographiques (site, volume, saignement actif), les artères embolisées etle type d'embol, le résultat clinique immédiat, les complications et la mortalité en cours d'hospitalisation .Résultats: 28 patients (âge moyen 75 ans) ont été embolisés. Tous les patients avaient un traitement anticoagulant et/ou antiplaquettaire. La majorité des hématomesembolisés concernaient le muscle grand droit de l'abdomen. Le saignement actif n'était pas identifié chez tous les patients au CT. Pas de complication immédiaterapportée. Le succès technique était de 98%. Pas de récidive précoce rapportée y compris après réintroduction du traitement anticaogulant.Conclusion: L'embolisation hémostatique des hématomes musculaires spontanés sous anticoagulants est efficace pour contrôler le saignement et permettre la réintroductiondu traitement anticoagulant