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Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model
INTRODUCTION: The inducible nitric oxide synthase (iNOS) plays a crucial role in early sepsis-related microcirculatory dysfunction. Compared to a catecholamine therapy we tested effects of a specific iNOS-inhibitor (1400W) on the microcirculatory function in the brain. METHODS: Seventy SD-rats (280-...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750197/ https://www.ncbi.nlm.nih.gov/pubmed/19709421 http://dx.doi.org/10.1186/cc8020 |
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author | Rosengarten, Bernhard Wolff, Stephanie Klatt, Sabine Schermuly, Ralf T |
author_facet | Rosengarten, Bernhard Wolff, Stephanie Klatt, Sabine Schermuly, Ralf T |
author_sort | Rosengarten, Bernhard |
collection | PubMed |
description | INTRODUCTION: The inducible nitric oxide synthase (iNOS) plays a crucial role in early sepsis-related microcirculatory dysfunction. Compared to a catecholamine therapy we tested effects of a specific iNOS-inhibitor (1400W) on the microcirculatory function in the brain. METHODS: Seventy SD-rats (280-310 g) were divided into 1 control and 6 sepsis groups. Sepsis groups received 1 or 5 mg/kg lipopolysaccharide (LPS) intravenously to induce a moderate or severe sepsis syndrome. Thirty minutes later rats were further randomized into subgroups receiving moderate volume therapy alone or additionally continuous norepinephrine (NE) or 1400W infusion. Separately, effects of 1400W on neurofunctional parameters were investigated in 3 rats without sepsis induction. Performing electric forepaw-stimulation evoked potentials (N2-P1 amplitude, P1-latency) and local hemodynamic responses were recorded with surface electrodes and laser Doppler over the somatosensory cortex at baseline and repeatedly after LPS administration. Cytokine levels (tumor necrosis factor-alpha (TNFα), interleukin-6 (IL6), interferon-gamma (IFNγ)) and cell destruction markers (neuron-specific enolase (NSE), S-100 calcium binding protein B (S100B)) were obtained at the end of experiments. RESULTS: During sepsis progression resting cerebral blood flow increased and functionally activated hemodynamic responses decreased in a dose-dependent manner. Whereas 1400W and NE improved blood pressure, only 1400W stabilized resting flow levels. However, both regimens were ineffective on the functionally coupled flow responses and destruction markers were similar between groups. CONCLUSIONS: NE and 1400W appeared to be ineffective in mitigating the effects of sepsis on the neurovascular coupling. Other regimens are needed to protect the cerebral microcirculation under septic conditions. |
format | Text |
id | pubmed-2750197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27501972009-09-25 Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model Rosengarten, Bernhard Wolff, Stephanie Klatt, Sabine Schermuly, Ralf T Crit Care Research INTRODUCTION: The inducible nitric oxide synthase (iNOS) plays a crucial role in early sepsis-related microcirculatory dysfunction. Compared to a catecholamine therapy we tested effects of a specific iNOS-inhibitor (1400W) on the microcirculatory function in the brain. METHODS: Seventy SD-rats (280-310 g) were divided into 1 control and 6 sepsis groups. Sepsis groups received 1 or 5 mg/kg lipopolysaccharide (LPS) intravenously to induce a moderate or severe sepsis syndrome. Thirty minutes later rats were further randomized into subgroups receiving moderate volume therapy alone or additionally continuous norepinephrine (NE) or 1400W infusion. Separately, effects of 1400W on neurofunctional parameters were investigated in 3 rats without sepsis induction. Performing electric forepaw-stimulation evoked potentials (N2-P1 amplitude, P1-latency) and local hemodynamic responses were recorded with surface electrodes and laser Doppler over the somatosensory cortex at baseline and repeatedly after LPS administration. Cytokine levels (tumor necrosis factor-alpha (TNFα), interleukin-6 (IL6), interferon-gamma (IFNγ)) and cell destruction markers (neuron-specific enolase (NSE), S-100 calcium binding protein B (S100B)) were obtained at the end of experiments. RESULTS: During sepsis progression resting cerebral blood flow increased and functionally activated hemodynamic responses decreased in a dose-dependent manner. Whereas 1400W and NE improved blood pressure, only 1400W stabilized resting flow levels. However, both regimens were ineffective on the functionally coupled flow responses and destruction markers were similar between groups. CONCLUSIONS: NE and 1400W appeared to be ineffective in mitigating the effects of sepsis on the neurovascular coupling. Other regimens are needed to protect the cerebral microcirculation under septic conditions. BioMed Central 2009 2009-08-26 /pmc/articles/PMC2750197/ /pubmed/19709421 http://dx.doi.org/10.1186/cc8020 Text en Copyright ©2009 Rosengarten et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Rosengarten, Bernhard Wolff, Stephanie Klatt, Sabine Schermuly, Ralf T Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
title | Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
title_full | Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
title_fullStr | Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
title_full_unstemmed | Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
title_short | Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
title_sort | effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750197/ https://www.ncbi.nlm.nih.gov/pubmed/19709421 http://dx.doi.org/10.1186/cc8020 |
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