The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury

Introduction: Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI. Methods: This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 micro g/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT. Results: Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-alpha and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-alpha: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups. Conclusions: We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option

Thoracic epidural anesthesia in sepsis – is it harmful or protective?

Research interest in epidural anesthesia during sepsis has grown over the past years and studies have tried to determine its mechanisms, which should, theoretically, protect organs and reduce morbidity and mortality. However, different experimental approaches in different animal models have provided conflicting results over whether epidural anesthesia has protective or harmful effects and whether these alter depending on the phase of sepsis, the spread of epidural anesthesia or additional supportive therapies. In the future, more standardized research is necessary to integrate the results of all studies, which have been published

Unterstützung krankenhausinterner Arbeitsprozesse mittels Workflow-Managementsystemen und Integration Sensor-basierter Geräte

Die exakte, automatisierte Erfassung und Abrechnung von Ressourcen wie Personal oder Material pro Patient wird für Krankenhäuser immer wichtiger. In dieser Arbeit wird eine Architektur vorgestellt, die es ermöglicht, krankenhaus-interne Arbeits-Prozesse durch sensorbasierte Geräte zu steuern und damit Abrechnungsdaten zu erfassen. Dabei werden neuste Techniken und Technologien aus dem Workflow-Management eingesetzt, die in der Lage sind, neben Control-Flowund Data-Routing-Patterns auch Resource-Patterns zu verwalten. Weitere wichtige Kennzeichen des Systems sind die Integration von sensorbasierten Geräten in das Workflow-Management-System sowie Techniken zur Modellierung von Workflows. Das System entsteht in enger Kooperation mit der Klinik und Poliklinik für Anästhesiologie und Intensivtherapie an der Universität Rostock. Basis des vorzustellenden Systems ist eine Architektur, die im Rahmen des RADIX-Projektes konzipiert wird. RADIX ist ein Verbundprojekt von GECKO mbH Rostock und dem ZGDV e.V. Rostock, in dem ein System zur Verwaltung und Steuerung heterogener Dokument- (ePaper, PapierAkten) und Prozessstrukturen innerhalb ebenenübergreifender Behördenumgebungen entwickelt wird

B beta(15-42) (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion

Objective:  The fibrin-derived peptide B beta(15-42) (also called FX06) has been shown to reduce myocardial infarct size following ischemia/reperfusion. Hemorrhagic shock (HS) followed by volume resuscitation represents a similar scenario, whereby a whole organism is vulnerable to reperfusion injury. Design: We subjected male farm-bred landrace pigs (similar to 30 kg) to HS by withdrawing blood to a mean arterial pressure of 40 mm Hg for 60 minutes. Pigs were then resuscitated with shed blood and crystalloids for 60 minutes, and at this time, FX06 (2.4 mg/kg, n = 8) or vehicle control (phosphate buffered saline; 2.4 mg/kg, n = 7) was injected as an intravenous bolus. Setting:  University hospital laboratory. Subjects:  Anesthetized male farm-bred landrace pigs. Measurements and Main Results:  Data are presented as mean +/- So. Five hours after resuscitation, controls presented acute lung injury (Pao(2)/Fio(2)-ratio *400 mm Hg; extra-vascular lung water index: *5.2 +/- 2.1 mL/kg, cardiac index: *6.3 +/- 1.4 L/min/m(2); stroke volume index: *51 +/- 11 mL/m(2); cardiac TnT levels: *0.11 +/- 0.09 ng/mL; *p <0.05). Also, tissue oxygenation (tp0(2); mm Hg) was significantly improved during reperfusion in FX06-treated pigs when compared with controls (liver 51 +/- 4 vs. *65 +/- 4; serosa 44 +/- 5 vs. *55 +/- 7; mucosa 14 +/- 4 vs. *26 4). Finally, FX06 reduced accumulation of mye loperoxidase- positive cells (mainly neutrophils) in myocardium, liver, and small intestine and reduced interleukin-6 plasma levels (*p <0.05; compared with controls). Conclusion:  We conclude that in a pig model of HS and reperfusion, administration of FX06 during reperfusion protects shock-susceptible organs such as heart, lung, liver, and small intestine. (Crit Care Med 2009; 37:598-605