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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric Oxide (NO) has been implicated in the pathologic vasodilation of sepsis. Because NO can be measured in the exhaled gas of animals and humans, we hypothesized that increases in exhaled NO would occur in a septic model. Using a blinded design, 10 male Sprague-Dawley rats (300 to 400 g) were anesthetized, paralyzed, tracheotomized, and randomized (5/group) to receive an intravenous injection of either lipopolysaccharide (LPS) (Salmonella typhosa, 20 mg/kg) or placebo (equal volume of saline). Thereafter, exhaled gas was collected and measurements of NO concentration were made using chemiluminescence every 20 min for 300 min during ventilation (RR 40 breaths/min, VT 3 ml; PEEP 0, FIO2 0.21). Another group of 10 animals (5 LPS; 5 control) were treated in the same fashion and then killed at 240 min and an arterial blood sample obtained for blood gas and TNF alpha determinations. Pressure volume (PV) curves were constructed and lungs removed, preserved, and submitted for histologic evaluation. LPS-treated rats had lower mean arterial pressures than the control group, p < 0.0001. No significant differences in static lung compliance and PV curves were found in the two groups. TNF alpha levels were greater in the LPS group (1.40 +/- 0.24 ng/ml) versus control group (0.09 +/- 0.04 ng/ml), p < 0.001. By contrast to the control group, exhaled NO concentration rose in all LPS-treated rats at approximately 100 min and at about 160 min reached a plateau that was 6 times greater than control levels (p < 0.0001). There was greater interstitial, airspace, and total lung injury in the LPS group (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased nitric oxide in exhaled gas as an early marker of lung inflammation in a model of sepsis. 753 2

We describe a technique that utilizes electron paramagnetic resonance (EPR) to measure NO(*) and pO(2) directly, and non-invasively, from tissue in vivo. Diethyldithiocarbamate (DETC) was injected with iron so as to complex with NO(*) in the tissue. Gloxy (an oxygen-sensitive, paramagnetic material) was also implanted into the tissue of interest (brain or liver). Because the signals arising from gloxy and NO-Fe-(DETC)(2) did not overlap, they could be monitored and measured simultaneously in vivo. The gloxy was not responsive to NO(*) and/or DETC. As model systems we either injected SNP (an NO(*) donor) into animals and monitored NO(*) and pO(2) simultaneously from brain, or endotoxin (lipopolysaccharide; LPS) was injected in order to induce a septic episode and NO(*) and pO(2) measured from liver. We found a close correlation between levels of SNP-derived NO(*) and brain pO(2) in vivo. During sepsis, liver pO(2) decreased dramatically at 300-360 min after endotoxin injection, and this coincided with decreases in mean arterial blood pressure and increased tissue NO(*) detected. These studies demonstrate the potential usefulness of this technique for making direct in vivo measurements of NO(*) and pO(2) simultaneously from tissue.
Nitric Oxide 1999 Aug
PMID:Simultaneous measurement of NO(*) and PO(2) from tissue by in vivo EPR. 1044 68

In vivo EPR was used to investigate liver oxygenation in a hemodynamic model of septic shock in mice. Oxygen-sensitive material was introduced either (i) as a slurry of fine particles which localized at the liver sinusoids (pO2 = 44.39 +/- 5.13 mmHg) or (ii) as larger particles implanted directly into liver tissue to measure average pO2 across the lobule (pO2 = 4.56 +/- 1.28 mmHg). Endotoxin caused decreases in pO2 at both sites early (5-15 min) and at late time points (6 h after endotoxin; sinusoid = 11.22 +/- 2.48 mmHg; lobule = 1.16 +/- 0.42 mmHg). The overall pO2 changes observed were similar (74.56% versus 74.72%, respectively). Blood pressures decreased transiently between 5 and 15 min (12.88 +/- 8% decrease) and severely at 6 h (59 +/- 9% decrease) following endotoxin, despite volume replacement with saline. Liver and circulatory nitric oxide was elevated at these times. Liver oxygen extraction decreased from 44% in controls to only 15% following endotoxin, despite severe liver hypoxia. Arterial oxygen saturation, blood flow (hepatic artery), and cardiac output were unaffected. Pretreatment with l-NMMA failed to improve endotoxin-induced oxygen defects at either site, whereas interleukin-13 preserved oxygenation. These site-specific measurements of pO2 provide in vivo evidence that the principal cause of liver hypoxia during hypodynamic sepsis is reduced oxygen supply to the sinusoid and can be alleviated by maintaining sinusoidal perfusion.
Nitric Oxide 2002 Feb
PMID:Endotoxin-induced liver hypoxia: defective oxygen delivery versus oxygen consumption. 1182 31

Nitric oxide (NO) is a gas that transmits signals in the organism. Such signal transmission takes place by means of the gas synthesis and release in different cell types. After it is released, the gas penetrates the membrane of a neighboring cell and regulates its function. Such mechanism represents an entirely new signaling principle in biological systems. The discoverers of NO as a signaling molecule were awarded the Nobel Prize in Medicine and Physiology in 1998. This discovery has revolutionized medicine and originated new treatments for old problems. In this study, we review the role of NO in some pathologies such as sepsis, arterial hypertension and pulmonary hypertension and Nitric Oxide is explained in terms of its current merit for treatment and its impact on nursing care.
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PMID:[Therapeutic use of nitric oxide: implications for nursing]. 1204 61

Catecholamines are elaborated in stress responses to mediate vasoconstriction, and elevate systemic vascular resistance and blood pressure. They are elaborated in disorders such as sepsis, cocaine abuse, and cardiovascular disease. The aim of the study was to determine whether catecholamines affect nitric oxide (NO) production, as NO is a vasodilator and counteracts the harmful effects of catecholamines. RAW264.7 macrophage cells were cultured with lipopolysaccharide (LPS)+/-epinephrine, norepinephrine, and dopamine at 5x10(-6)M concentrations for 24h. Supernatants were harvested for measuring NO by spectrophotometry using the Greiss reagent and cells were harvested for detecting inducible NO synthase (iNOS) by Western blot. NO production in RAW 264.7 macrophages was increased significantly by addition of LPS (0.5-10ng/ml) in a dose-dependent fashion. The NO production induced by LPS was further enhanced by epinephrine and norepinephrine, and to a lesser extent by dopamine. These increases in NO correlated with expression of iNOS protein in these cells. The enhancing effect of iNOS synthesis by epinephrine and norepinephrine on LPS-induced macrophages was down regulated by beta-adrenoceptor antagonist, propranolol, and dexamethasone. The results suggest that catecholamines have a synergic effect on LPS in induction of iNOS synthesis and NO production, and this may mediate some of the vascular effects of infection. These data support a novel role for catecholamines in disorders such as septic shock and cocaine use, and indicate that beta-adrenoceptor antagonists and glucocorticoids may be used therapeutically for modulation of the catecholamine-NO axis in disease states.
Nitric Oxide 2003 Mar
PMID:Regulation of nitric oxide production from macrophages by lipopolysaccharide and catecholamines. 1262 Mar 76

Stenotrophomonas maltophilia is an emerging pathogen implicated in an increasing number of severe pulmonary infections and nosocomial sepsis. We evaluated the influence of four different antibiotics on the bacterial count and LPS activity found in broth cultures of S. maltophilia. After 4 h ceftazidime (CTZ) decreased live bacteria but increased endotoxin activity, whilst isepamicin (ISE), tobramycin (TB), and polymyxin B (PB) reduced both of them. We also investigated the influence of the above mentioned antibiotics on the ability of S. maltophilia culture filtrates and S. maltophilia LPS, extracted in our laboratory, to stimulate sepsis mediators such as tumor necrosis factor a (TNF-a), interleukin 8 (IL-8), interleukin 10 (IL-10), Nitric Oxide (NO) and as bactericidal/permeability-increasing protein (BPI) in human whole blood. Our results demonstrated that both single polycationic antibiotics and the combination of two molecules are able to kill bacteria and neutralize released S. maltophilia LPS. Combination between beta-lactams and aminoglycosides is often able to reduce the pro-inflammatory effects of S. maltophilia culture filtrates.
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PMID:Stenotrophomonas maltophilia lipopolysaccharide (LPS) and antibiotics: "in vitro" effects on inflammatory mediators. 1572 12

Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a "vital poison" for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N(G)-methyl-l-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-to-day care resuscitative measures.
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PMID:Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies. 1603 66

Staphylococcus aureus is a highly virulent human pathogen with an extensive array of strategies to subvert the innate immune response. An important aspect of innate immunity is the production of the nitrogen monoxide radical (Nitric Oxide, NO.). Here we describe an adaptive response to nitrosative stress that allows S. aureus to replicate at high concentrations of NO.. Microarray analysis revealed 84 staphylococcal genes with significantly altered expression following NO. exposure. Of these, 30 are involved with iron-homeostasis, potentially under the control of the Fur regulator. Another seven induced genes are involved in hypoxic/fermentative metabolism, including the flavohaemoprotein, Hmp. The SrrAB two-component system has been shown to regulate the expression of many of the NO.-induced metabolic genes. Indeed, inactivation of hmp, srrAB and fur resulted in heightened NO. sensitivity. Hmp was responsible for c. 90% of measurable staphylococcal NO. consumption and therefore critical for efficient NO. detoxification. While SrrAB was required for maximal hmp expression, srrAB mutants still exhibited significant NO. scavenging and NO.-dependent induction of hmp. Yet S. aureus lacking SrrAB were more sensitive to nitrosative stress than hmp mutants, indicating that the contribution of SrrAB to NO. resistance extends beyond the regulation of hmp expression. Both Hmp and SrrAB were required for full virulence in a murine sepsis model, however, only the attenuation of the hmp mutant was restored by the abrogation of host NO. production. Thus, the S. aureus Hmp protein has evolved to serve as an iNOS-dependent virulence determinant.
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PMID:The nitrosative stress response of Staphylococcus aureus is required for resistance to innate immunity. 1685 93

Nitric oxide (NO) plays an important role in the pathophysiology of sepsis and septic shock but the mechanism is not well understood. The aim of this study was to investigate the role of NO in the cytochrome P450 (CYP) isozyme activity and the expression of its gene during polymicrobial sepsis. The rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). Aminoguanidine (AG, 100 mg/kg body weight) or N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg body weight) was injected intraperitoneally at 0, 3, 6, 10, and 20 h after CLP. The plasma nitrite/nitrate concentration increased 24 h after CLP, and this increase was almost completely abolished by AG and L-NAME. Sepsis increased the serum aminotransferase and lipid peroxidation levels, which were attenuated by AG but augmented by L-NAME. The hepatic concentration of the reduced gluthathione decreased in the CLP rats, which was inhibited by AG but augmented by L-NAME. The total CYP content decreased after CLP, which was restored by AG and L-NAME. The CYP1A1, 1A2, and 2E1 activities, along with their protein levels, decreased 24 h after CLP but these decreases were reversed by AG and L-NAME. The CYP1A1, 1A2, 2B1, and 2E1 mRNA expression levels decreased 24 h after CLP, and L-NAME inhibited this decrease. NO plays a key role in the sepsis-mediated decrease in CYP via the interplay of two different mechanisms: NO-dependent suppression of protein via the enhanced inducible NO synthase, and NO-dependent transcriptional suppression via endothelial NO synthase.
Nitric Oxide 2006 Dec
PMID:Role of nitric oxide in the inhibition of liver cytochrome P450 during sepsis. 1688 34

This study examined the role of nitric oxide (NO) on the expression of the hepatic vasoregulatory gene during polymicrobial sepsis. Aminoguanidine (AG, 100 mg/kg) or Nomega-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) was injected intraperitoneally at 0, 3, 6, 10, and 20 h after a cecal ligation and puncture (CLP). The heart rate increased 24 h after the CLP, and this increase was attenuated by L-NAME and further attenuated by AG. The mean arterial pressure in the CLP animals did not change significantly 24 h after the onset of sepsis but was increased after the L-NAME injection. Sepsis increased the serum aminotransferase levels, which were attenuated by AG but augmented by L-NAME. CLP increased the mRNA level of the ET-1 and ETB receptors in the liver. This increase was prevented by AG but augmented by L-NAME. The level of iNOS and HO-1 mRNA expression were increased by CLP, which was prevented by both AG and L-NAME. The level of TNF-alpha and COX-2 mRNA expression increased after CLP, and was attenuated by AG. These results show that iNOS and eNOS are regulated differently in sepsis. While eNOS appears to have a protective role in liver microcirculation, the strong upregulation of iNOS might contribute to a microvascular dysfunction and hepatic injury.
Nitric Oxide
PMID:Role of nitric oxide in the expression of hepatic vascular stress genes in response to sepsis. 1788 72


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