摘要:

Healthy physiological systems exhibit irregular variability whereas diseased systems display decreased signal variability or greater regularity. The objective of this article is to report a case series of critically ill adults who displayed ultra low-frequency periodic sinusoidal oscillations in cardiac output (ULF-CO) that were discovered during a clinical study testing software for continuous physiological monitoring. Data were collected from 13 critically ill surgical and trauma patients who required continuous cardiac output monitoring. Physiologic data were collected from clinical monitors. The computerized time series of cases displaying CO oscillations were manually reviewed. Ten patients with sepsis or the systemic inflammatory response syndrome exhibited 18 episodes of ultra low-frequency periodic oscillations (ULF-CO) with frequencies ranging from 0.0028 to 0.000053 Hz (periods, 6 to 316 min). Intensive care unit mortality rate was 50%. The amplitude and coefficient of variation of cardiac output during ULF-CO ranged from 0.1–4.6 L and 3.9–14.3%, respectively. Duration of ULF-CO ranged from 4–108.1 h. ULF-CO could not be explained as a result of patterned artifact from measurement error or therapeutic intervention. ULF-CO may be a pathophysiologic marker that might serve the diagnosis, prognosis, and treatment of critical illness.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The treatment of acute respiratory failure in infants by means of extracorporeal membrane oxygenation (ECMO) is thought to be associated with a treatment-related inflammatory reaction, which may deteriorate the underlying disease process. The aim of this study was to compare the venoarterial (VA) and venovenous (VV) modality of ECMO with regard to their pulmonary and serological cytokine release during rescue from acute hypoxia. The inflammatory response was measured in piglets undergoing hypoxic ventilation with a gas mixture of 92% N2and 8% O2, which were then rescued through VA- (n = 5) or VV-ECMO (n = 5). The effect of cannulation and anesthesia on the inflammatory response was deducted from regularly ventilated control animals (n = 5). The concentrations of the proinflammatory interleukins (IL)-1&bgr; and IL-8 increased in the bronchoalveolar lavage fluid of all groups over a study period of 5 h but were significantly higher (P< 0.05) during VA-ECMO treatment, whereas the anti-inflammatory IL-10 concentrations were significantly higher in the bronchoalveolar lavage fluid of VV-treated animals (P< 0.001). No statistical difference between groups was found in the serum concentrations of cytokines. We conclude that in this animal model rescue from hypoxia by means of the VA modality of ECMO leads to a more pronounced inflammatory reaction of the lung than when applying the VV modality.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Heme oxygenase-1 (HO-1) is a stress response protein that is highly inducible under various conditions, such as oxidative or heat stress. The present study investigated expression pattern and regulation of HO-1 in human liver. Expression pattern of HO-1 immunoreactive protein was studied in liver biopsies by immunohistochemistry, revealing constitutive expression in Kupffer cells but not in hepatocytes. HO-1 was, however, inducible in hepatocytes and vascular tissue under pathological conditions, e.g. associated with fatty degeneration or liver malignancies. Regulation of HO-1 gene expression was further studied by Northern blot analysis in HepG2 cells and freshly isolated peripheral blood mononuclear cells as model systems of parenchymal and nonparenchymal liver cell populations, respectively. HO-1 mRNA was inducible in HepG2 cells and mononuclear cells by various agents inducing oxidative stress. However, HO-1 gene expression was not inducible by heat shock. Pyrrolidine dithiocarbamate, an inhibitor of nuclear factor &kgr;B-dependent gene expression, dose dependently decreased HO-1 mRNA transcripts in human mononuclear cells subjected to oxidative stress while slightly increasing HO-1 gene expression in HepG2 cells. In contrast, HO-1 induction upon oxidative stress was attenuated in HepG2 cells by cycloheximide and dexamethasone. Although activator protein-1 has been reported as the predominant redox-sensitive transcription factor inducing HO-1 expression in murine macrophages, nuclear factor &kgr;B seems to play a significant role in human mononuclear cells. Our data are consistent with a role for activator protein-1in HO-1 induction in human HepG2 hepatoma cells. These data suggest a differential regulation of HO-1 gene expression in parenchymal and non-parenchymal human liver cells and may provide a topographic basis for the understanding of the role of the heme oxygenase/carbon monoxide pathway in human liver disease.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Substantial clinical and laboratory research has revealed that major injury causes abnormalities in both the innate and adaptive immune systems. However, the relative importance of each of these systems in the immune dysfunction after injury is poorly understood and difficult to establish by clinical studies alone. Rag1 (−/−) C57BL/6 mice (Rag1), which lack an adoptive immune system, and immune-sufficient wild-type (WT) C57BL/6 mice underwent 25% total body surface area burn injury or sham injury under anesthesia and were subjected to cecal ligation and puncture (CLP) at day 10 postinjury, a time of high CLP mortality in this model. To test the effect of adaptive immune deficiency on inflammatory cytokine production after injury, adaptive cell-depleted splenocytes from sham and burn WT and Rag1 mice were stimulated with LPS, and TNF-&agr; and IL-6 production were assayed at days 1 and 7 postinjury. Intracellular expression of TNF&agr; and IL-6 by F4/80 macrophages was also assessed on day 7 by intracellular cytokine staining. Finally, Rag1 animals were reconstituted with WT splenocytes, and the effect of such reconstitution on CLP survival and cytokine production was determined. Survival of sham WT animals after CLP was significantly higher (P< 0.01) than survival of burn WT and Rag1 sham and burn animals, all of which had equivalently low survival. Reconstitution of Rag1 animals with WT splenocytes restored CLP survival to WT sham levels. Splenocytes from Rag1 burn mice showed significantly augmented cytokine production when compared with WT burn mice on day 7 (P< 0.05). Reconstitution of Rag1 mice with WT splenocytes at the time of injury returned cytokine production to WT levels. Intracellular cytokine expression in F4/80 macrophages was increased to a similar degree after burn, but not sham burn injury in Rag1, reconstituted Rag1 and WT animals. These studies demonstrate that the adaptive immune system is necessary for protection from polymicrobial sepsis and plays a significant role in regulating the inflammatory response to injury.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

CD10, also known as neutral endopeptidase or CALLA, is a major metalloproteinase that regulates levels of biologically active peptides that initiate inflammatory, cardiovascular, and neurogenic responses. Relative tissue expression levels of CD10, its peptide substrates, and their receptors constitute the basic regulatory mechanism. Neutrophils contain abundant CD10 and are rapid responders to an inflammatory septic challenge. Expression of neutrophil surface antigens in response to inflammation was studied in the primate model ofEscherichia coli-mediated sepsis and in human volunteers injected with lipopolysaccharide (LPS). There was a rapid and profound (up to 95%) reduced baboon neutrophil CD10 expression in response toE. coliinjections of 5.71 × 106CFU/kg to 2.45 × 109CFU/kg that gradually resolved to preinjection levels. The reduction was both dose and time dependent. Reduced CD10 antigen on mature baboon neutrophils and bands was observed by immunohistochemistry. Human volunteers challenged with 4ng/kg LPS experienced transient chills, nausea, fever, and myalgia. Up to ∼20% of their neutrophils had reduced CD10 expression, peaking at 2 to 8 h after injection. By 24 h, neutrophil CD10 expression resolved to preinjection levels. In contrast, in both the baboon and human studies, other neutrophil surface antigens were only slightly decreased (CD11a) or increased (CD11b, CD18, CD35, CD66b, and CD63). These data present the novel observation that neutrophil CD10 expression decreases significantly in response toin vivoinflammatory challenge. This decrease appears to be unique to CD10 and may contribute to a reduced regulation of bioactive peptides released in response to inflammatory challenge.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Shock is associated with a dramatic rise in the level of inflammatory mediators found in plasma. The exact source of these mediators has remained uncertain. We recently examined a previously undescribed mechanism for production of inflammatory mediators in shock involving pancreatic digestive enzymes. The currentin vitrostudy was designed to identify particular pancreatic enzymes and organs that may potentially produce inflammatory mediators. A selection of different organs from the rat (heart, liver, brain, spleen, pancreas, intestine, diaphragm, kidney, and lung) were homogenized and incubated with purified trypsin, chymotrypsin, elastase, lipase, nuclease, or amylase and the supernatant was incubated with fresh naïve leukocytes for 15 min. The level of leukocyte activation in the form of pseudopod formation and the fraction of cell death were measured. Without the addition of purified enzymes, only the homogenate of the pancreas yielded enhanced cell activation. Organs incubated with physiological concentrations of trypsin also stimulated significantly higher levels of pseudopod formation as compared with the undigested organs or enzymatic controls. Lipase and chymotrypsin were able to elicit cellular activation from selected organs such as the heart, intestine, liver and diaphragm. Undigested pancreatic homogenates were capable of producing substantial cell death, as compared with all other undigested organs. Intestinal digests with elastase, lipase, trypsin and chymotrypsin also stimulated significant cell mortality. Lipase-treated heart, liver, intestine, diaphragm, kidney, and lung stimulated cell death as well. We conclude that the intestine, as well as several other organs, may serve as a major source of inflammatory mediators during shock if exposed to digestive enzymes.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Gender differences in immune and organ functions have been described in different rodent models of trauma- and pressure-controlled hemorrhagic shock. We hypothesized that gender influences the regulation of plasma and tissue fluids in rats under such conditions. To study this we used male and weight matched proestrus female Sprague-Dawley rats, which were assigned to three groups (n = 7/group): sham, maximal bleedout (trauma and 45 min of blood pressure at 35 mmHg without resuscitation), or 5 h after completion of trauma–hemorrhage and resuscitation. Trauma-hemorrhage involved midline laparotomy and approx. 90 min of hemorrhagic shock (35 mmHg), followed by fluid resuscitation (4× the shed blood volume with Ringers lactate).51Cr-EDTA,125I-albumin distribution, and wet weight/dry weight were used to calculate plasma volume and extracellular fluid volume and cellular water content. Proestrus female rats showed significantly higher plasma volumes compared with weight-matched males. The volume of blood withdrawn in the first 15 min of hemorrhagic shock was significantly less in proestrus females compared with males; however, there was no significant difference in the total shed blood volume. Moreover, proestrus females showed less interstitial edema formation compared with male rats at 5 h after resuscitation. We conclude that differences in the regulation of plasma and tissue volumes exist between males and proestrus females during and after trauma-hemorrhage. The increased circulating blood volume could contribute the improved immune and organ functions in proestrus females under those conditions.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Reperfusion of ischemic tissue often leads to an acute inflammatory response, which acts directly to aggravate the injury in the reperfused zone, characterized by adhesion and subsequent infiltration of inflammatory cells that injure the tissue through the generation of oxygen-derived free radicals and release of various inflammatory mediators. The rapid edema formation associated with reperfusion injury is induced by increased microvascular permeability to plasma proteins and/or increased net filtration pressure across the microvascular wall, and the latter is at least in part induced by lowering of the interstitial fluid pressure (Pif). We investigated the anti-inflammatory effect of &agr;-trinositol (D-myo-inositol-1,2,6-trisphosphate) on edema formation, microvascular protein leakage, and Pifin rat hind limb after ischemia-reperfusion (I/R) injury. There was significant increase of both albumin extravasation from 0.02 ± 0.02 to 0.41 ± 0.21 mL g dry weight−1(P< 0.05) and total tissue water from 1.08 ± 0.07 to 1.65 ± 0.55 mL g dry weight−1(P< 0.05) in the skin of paws undergoing I/R injury. Pifwas significantly lowered from −0.51 ± 0.34 to −5.00 ± 1.53 mmHg (P< 0.05) concomitant with substantial edema formation. The edema formation, and lowering ofPifduring I/R injury was significantly lowered and nearly totally abolished in the animals treated with &agr;-trinositol 30 min before reperfusion. We conclude that &agr;-trinositol limits the increased vascular permeability and edema formation by preventing the decrease inPifas well as acting protective on the microvascular wall.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Endogenous copper can play an important role in postischemic reperfusion injury, a condition associated with endothelial cell activation and increased interleukin 8 (IL-8) production. Excessive endothelial IL-8 secreted during trauma, major surgery, and sepsis may contribute to the development of systemic inflammatory response syndrome (SIRS), adult respiratory distress syndrome (ARDS), and multiple organ failure (MOF). No previous reports have indicated that copper has a direct role in stimulating human endothelial IL-8 secretion. Increased IL-8 in the culture medium of human umbilical vein (HUVEC), lung microvascular, and iliac artery endothelial cells was observed 24 h after the addition of 10 to 50 &mgr;M CuCl2(cupric ions). HUVEC IL-8 induction by copper was higher than by 50 pg/mL tumor necrosis factor-&agr;, whereas 50 pg/mL IL-1&bgr; and 1 ng/mL platelet-activating factor did not stimulate IL-8 production or release. HUVEC IL-8 mRNA increased 3 h after CuCl2stimulation and remained elevated after 24 h, implying sustained transcriptional activation. Copper did not stimulate HUVECs to secrete other cytokines. Cu(II) appeared to be the primary copper ion responsible for the observed increase in IL-8 because a specific high-affinity Cu(II)-binding peptide, d-Asp-d-Ala-d-His-d-Lys (d-DAHK), completely abolished this effect in a dose-dependent manner. These results suggest that Cu(II) may induce endothelial IL-8 by a mechanism independent of known Cu(I) generation of reactive oxygen species. Furthermore,in vivostudies are warranted to determine if copper is involved in the pathogenesis of systemic inflammation and if Cu(II) chelation can reduce this IL-8-induced endothelial inflammatory response.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

It has been demonstrated that biopterin, an essential cofactor of nitric oxide synthase (NOS), plays an important role in the pathogenesis of endotoxin-induced shock, yet its biological significance in gram-positive sepsis remains unclear. In this study, we adopted a rat model of postburnStaphylococcus aureussepsis to investigate the potential role of biopterin in the pathogenesis of gram-positive sepsis. Wistar rats were inflicted with a 20% total body surface area (TBSA) full-thickness scald injury followed byS. aureuschallenge, and then guanosine triphosphate-cyclohydrolase I (GTP-CHI) mRNA expression and biopterin levels in liver, kidneys, lungs, and heart were determined. We found that afterS. aureuschallenge, GTP-CHI gene expressions and biopterin levels were markedly upregulated in various tissues. Meanwhile, multiple organ dysfunction was induced byS. aureuschallenge. It was shown that cardiac GTP-CHI mRNA expression and renal BH4levels were positively correlated with MB isoenzyme of creatine kinase (CK-MB) and creatinine (r= 0.892,P= 0.0012 andr= 0.9423,P= 0.0015, respectively). These results suggested that thermal injury combined withS. aureuschallenge could inducede novobiosynthesis of biopterin, which might play a role in the development of multiple organ dysfunction syndrome secondary to postburn sepsis.

ISSN:1073-2322    

出版商:OVID    

年代:2003

数据来源: OVID