Current vascular pharmacology
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Curr Vasc Pharmacol · Oct 2007
ReviewMicrocirculatory endothelial dysfunction during endotoxemia--insights into pathophysiology, pathologic mechanisms and clinical relevance.
Alterations in microcirculatory permeability are a characteristic of early tissue injury. Moreover, tissue edema is an early indicator of tissue dysfunction, prior to organ failure, because tissue edema is associated with impaired gas exchange, arterial hypoxemia, and may also impair tissue oxygen distribution. As a result of increased microvascular permeability, plasma fluid is lost into the interstitial space, leading to hypovolemia. ⋯ In this regard platelets, besides leukocytes, play a major role for the development of microvascular hyperpermeability. This review considers endothelial cell dysfunction during endotoxemia including current insights into sepsis pathophysiology. New aspects of this complex pathogenesis are illustrated and their relevance for clinical sepsis therapy is emphasized.
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Curr Vasc Pharmacol · Oct 2007
Near-infrared spectroscopy (NIRS): a non-invasive in vivo methodology for analysis of brain vascular and metabolic activities in real time in rodents.
Near infrared spectroscopy (NIRS) was first used as a tool for the in vivo monitoring of tissue oxygenation in the late seventies. Today, NIRS instruments are more and more used in clinical environments since they are now easy to use, sensitive, robust, provide rapid analysis and could be complementary to other non invasive methodologies such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). The feasibility of non-invasive analysis of brain activities is studied in the attempt to overcome the major limitation of invasive in vivo methodologies. ⋯ In addition, the possibility that changes in brain metabolism as measured by NIRS might be a useful index of brain penetration of new chemical entities has been investigated using different compounds from different chemical classes that were selected on the basis of their known brain penetration and overall pharmacokinetic profile. Finally, the feasibility of coupling NIRS with another although invasive in vivo method such as electrophysiology for concomitant analysis of cerebral cell firing in discrete brain areas was tested in the attempt to study in real time the putative correlation between blood levels, brain metabolism and neuronal activities in rat CNS, i.e. apply NIRS to pharmacodynamic investigations. The data gathered in rat treated with exogenous O(2), indicate an original relationship between NIRS analysis of brain metabolism and electrical changes in this major nucleus of CNS involved in neurophysiologic and pathologic activities.