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Patients with atrial fibrillation (AF) often present with typical angina pectoris and mildly elevated levels of cardiac troponin (non-ST-segment elevation myocardial infarction) during an acute episode of AF. However, in a large proportion of these patients, significant coronary artery disease is excluded by coronary angiography, which suggests that AF itself influences myocardial blood flow. The present review summarizes the effect of AF on the occurrence of ventricular oxidative stress, redox-sensitive signaling pathways and gene expression, and microcirculatory flow abnormalities in the left ventricle.
Das im Rahmen dieser Arbeit etablierte Verfahren zur morphometrischen Bewertung der lokalen Entzündungsreaktion nach Implantation von Biomaterialien stellt eine reproduzierbare, vielfältig anwendbare Methode dar. Das Programm ImageJ ermöglicht ein einfaches, modifiziertes Adaptieren dieses Analyseverfahrens an verschiedene immunhistochemische Untersuchungen. Die Anwendung des etablierten manuellen Zählverfahrens ermöglichte in den nachfolgenden Untersuchungen den Nachweis, dass das Konzept der Beschichtung von Implantatmaterialien mit einer biomimetischen Membran, basierend auf dem Phospholipid POPE, keine negativen Einflüsse auf die akute und chronische Entzündungsreaktion im das Implantat umgebenden Gewebe zeigte. Die Herstellung von biomimetischen Oberflächen als Implantatbeschichtung, die von den Zellen als körpereigen erkannt wird, könnte somit die langfristige Integration des Implantats in den Wirtsorganismus verbessern. Zusammen mit den In-vitro-Ergebnissen [Willumeit et al., 2007], in denen günstige Auswirkungen dieser Beschichtung auf Zell- und Bakterienadhäsion nachgewiesen wurden, zeigen die In-vivo-Befunde der vorliegenden Arbeit das Potential von Phospholipidbeschichtungen zum Erreichen von lang andauernder Integrität und Biofunktionalität metallischer Implantate in der klinischen Anwendung.
I have investigated the role played by reactive oxygen species (ROS) generated by the phagocyte NADPH oxidase system in the innate immune response. I first looked at effector functions by asking whether ROS released from phagocytes might be effective in the killing of extracellular bacteria. Since bacteria can be killed in many other ways – for example by proteases or by cationic peptides – I made use of the recently demonstrated capacity of ROS to remove discontinuities from the surface of gold as the basis of an in vivo assay for extracellular ROS. Unlike bacterial killing, this readout system is not affected by enzymes, cationic peptides or other biological anti-bacterial agents. By this means I was able to use wild type mice and a congenic strain which lacks the gene coding for the gp91 subunit of the phagocyte NADPH oxidase to demonstrate that ROS generated by the NADPH oxidase system are indeed found outside the cells during an inflammation in vivo and that their principle source is neutrophil granulocytes rather than tissue macrophages. Since ROS released by these cells will be non-specific in its action it is to be expected that the releasing cell will itself suffer considerable damage. This fits well to the known short life of activated neutrophils and may explain the established fact that their death is dependent on the NADPH oxidase system. The long lived macrophages, in contrast, restrict their production of extracellular ROS. ROS are increasingly being found to be involved in both intra and intercellular signalling processes I looked for an involvement of NADPH oxidase derived ROS in the recruitment of neutrophils to sites of inflammation in vivo. Since the gene coding for the gp91 subunit of the NADPH oxidase is on the X chromosome I made use of a mosaic expression strategy based on X chromosomal inactivation. The results show that indeed ROS serves as a component of the neutrophil recruitment process in the critical early stages of an infection. Possible mechanisms are explored.