摘要:

ABSTRACTThe authors measured the peripheral blood pro‐inflammatory cytokine responses (tumor necrosis factor‐&agr; [TNF‐&agr;] and interleukin‐6 [IL‐6]) and related end organ responses to intraperitoneal zymosan‐saline suspension over 5 days in CD‐1 mice. Other indicators of local and systemic inflammation included wet:dry weight ratios of lung, liver, kidneys, spleen, and bowel; peripheral blood hematocrit, white blood cell count, and platelet count; lung myeloperoxidase activity; lung protein leak; and bacterial translocation to liver, spleen, and mesenteric lymph nodes. The initial event in response to zymosan A injection was a sharp rise in the peripheral blood TNF‐&agr; level, which crested within 1 h of injection. This response was followed by a peripheral blood leukocytosis also within 1 h, and a peak lung myeloperoxidase activity within 1‐2 h of injection. The maximum lung permeability index occurred 8 h after injection (zymosan, .398 ± .019 [n ‐ 10]; saline vehicle, .266 ± .007 [n = 10], p < .001) followed by the maximum lung wet:dry weight ratio, which occurred 18 h after injection. The peak wet:dry weight ratios for the other organs occurred between 12 and 24 h after injection as well. Peripheral blood IL‐6 maxima followed TNF‐&agr; maxima after lags of several hours. The release of pre‐formed TNF‐&agr; is likely the most proximal event following injection of zymosan, and may set in motion the processes that result in end‐organ injury and secondary multiple organ dysfunction, particularly activation of leukocytes. The precise roles of TNF‐&agr; and IL‐6 in the pathogenesis of end‐organ injury, however, are not addressed.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTThis study aimed to determine the contribution of endogenous opiates to the hormonal and glucose metabolic response to lipopolysaccharide (LPS). Rats were infused with naloxone (NAL) (32 μg/h) for 2 h prior to the injection of LPS (100 μ/100 g body weight) and hemodynamic, hormonal, and metabolic parameters were determined. NAL produced no detectable alterations in any of the parameters assessed. LPS transiently decreased (26%) mean arterial blood pressure (MABP), and increased plasma glucose concentration (100‐130%), glucose rate of appearance (50‐100%), and glucose rate of disappearance (50‐100%). NAL did not alter the LPS‐induced drop in mean arterial blood pressure or the glucose response to LPS. LPS reduced plasma insulin (54%), and increased glucagon (270%), corticosterone (180%), and tumor necrosis factor concentrations in plasma (peak 3200‐4600 pg/mL at 90 min), with no modification by NAL pretreatment. These results suggest a lack of involvement of endogenous opiate pathways in the glucose metabolic and hormonal responses to LPS.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTThe influence of sepsis on polyamine metabolism in the liver was studied in rats. Sepsis was induced by cecal ligation and puncture; control rats were sham‐operated. Sepsis resulted in increased concentrations in liver tissue of putrescine and spermidine and stimulated activity of the enzymes ornithine decarboxylase (ODC) and s‐adenosylmethionine decarboxylase. A similar metabolic response was seen following the subcutaneous injection of 1 mg/kg of endotoxin or following the intraperitoneal injection of 100 μg/kg of human recombinant tumor necrosis factor (TNF)‐&agr; or interleukin‐1&agr; (IL‐1&agr;). ODC mRNA levels determined by Northern blots were increased in liver tissue of septic rats, suggesting that the increase in ODC activity may be regulated at the transcriptional level although increased stability of the messenger could give rise to similar results. Treatment of rats with either TNF antiserum, recombinant IL‐1 receptor antagonist, or the glucocorticoid receptor antagonist RU 38486, did not prevent the sepsis‐induced increase in hepatic ODC activity. The data suggest that sepsis stimulates the biosynthesis of polyamines in liver tissue and that this response to sepsis may not primarily be mediated by TNF, IL‐1, or glucocorti‐coids. The biological role of increased liver polyamines during sepsis, in particular their relationship with the synthesis of acute phase proteins, remains to be determined.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTEndothelins (ET) have been demonstrated to mediate intestinal microvascular constriction during acute Escherichia coli bacteremia, however, their role during chronic infection is unknown. The purpose of this study was to determine whether ET‐1 is synthesized in the small intestine in a more chronic peritonitis model. ET‐1 mRNA levels of the terminal ileum in mice following cecal ligation and puncture (CLP) were compared to sham‐operated animals and normal unoperated animals. ET gene expression was analyzed using differential reverse transcriptase chain reaction (RT‐PCR) with co‐amplification of &bgr;‐actin as an internal standard. To assess ET peptide expression, serum and intestinal tissue levels were measured using a specific enzyme immunoassay (ELISA). The pattern of ET‐1 gene expression post‐CLP with a single puncture of the cecum with a 23 ga. needle demonstrated a 3.6‐fold increase at 8 h, and a return to sham levels by 24 h (374 ± 64% at 8 h,p< .0%, 128 ± 13%). An increase of mRNA levels at 24 h post‐CLP was observed with a double puncture with an 18 ga. needle (230 ± 36%,p< .0%) accompanied by an increase in serum ET levels (270 ± 31%,p< .0%) and higher tissue ET levels. These data indicate a time‐dependent response of ET‐1 gene expression in the terminal ileum post‐CLP which is related to the severity of infection.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTNitric oxide synthase (NOS) inhibition has been used to increase blood pressure in humans with septic shock despite a lack of data regarding its effects on O2delivery (Qo2). We studied the effects of AG‐nitro‐L‐arginine methyl ester (L‐NAME) on systemic, gut, and hindlimb circulations of endotoxic dogs. Twelve dogs were infused with 2 mg/kg of LPS over 1 h followed by 60 mL/kg of 6% dextran over 2 h. Six dogs also received 20 mg/kg of L‐Name. LPS caused mean arterial pressure (MAP), flow, and Qo2to whole body, hindlimb and gut to decrease, but O2uptake (Vo2) did not change. Dextran resuscitation alone produced a hyperdynamic state with increased blood flow to or above baseline. With L‐Name, systemic and regional resistances increased twofold and MAP returned to near baseline. Late in the study, these dogs had significantly lower blood flow and Qo2to the gut but maintained Vo2by increasing oxygen extraction to near critical levels. These data suggest that in acute endotoxicosis, L‐Name may significantly improve blood pressure but may markedly encroach on O2transport reserves to the gut.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTThis study was designed to evaluate the effects of small‐volume infusion of 7.5% hypertonic saline/6% dextran‐70 (HSD) on the cardiovascular function of traumatic‐hemorrhagic shock rats at simulated high altitude. 32 rats were randomly divided into four groups: 1) normal saline (NS)‐treated group, 2) .9% NaCI/6% dextran‐70 (Dex)‐treated group, 3) 7.5% hypertonic saline (HS)‐treated group, and 4) 7.5% hypertonic saline/6% dextran‐70 (HSD)‐treated group. The rats were exposed to a simulated high altitude of 4,000 m in a hypobaric hypoxic chamber, and traumatic‐hemorrhagic shock was inflicted through fracture of the shaft of the left femur and bleeding from femoral vein to reduce mean arterial pressure (MAP) to 6.00 ± .67 kPa within 5 min. The MAP was kept at this level for 1 h, and then a bolus intravenous injection of 4 mL/kg NS, Dex, HS, or HSD were given to the rats, respectively. In the 5 h period after treatment, it was found that MAP, left ventricular systolic pressure, maximal rate of left ventricular pressure rise and drop (±dp/dfmax) were significantly higher in HSD group than in the NS, Dex, and HS groups. It can be concluded that 1) HSD can improve the cardiovascular function and hemodynamics of traumatic‐hemorrhagic shock rats at simulated high altitude and 2) HSD is more effective than HS.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTThe protective effects of hydroxyethyl starch‐conjugated deferoxamine (HES‐DFO), a macromolecular iron chelator, on the initial pathophysiological cascade in septic shock were evaluated following cecal ligation puncture (CLP) in rats. Animals were given an intravenous dose of 3.0 mL of either vehicle (HES) or HES‐DFO immediately following completion of the CLP procedure. Animals were sacrificed 30,60, 120, and 240 min following CLP, and samples of lung, kidney, bowel, and liver were collected for subsequent analysis of glutathione, myeloperoxidase, and evidence for lipid peroxidation based on measurement of thiobarbituric acid reactive substances and conjugated dienes. In addition, the endotoxin levels were determined in the plasma and histomorphological examination was conducted on tissue samples collected at each time point. At almost all time points, a reduction in lipid peroxidation was noted in the HES‐DFO‐treated rats (p< .05). Glutathione and myeloperoxidase levels were less affected. Lung tissue from animals receiving HES demonstrated marked microatelectases, septal destruction, and splicing of basal membranes, which were greatly attenuated in animals having received HES‐DFO. Similarly, tubulotoxic and mitochondrial damages observed in kidney samples from HES‐treated animals were noticeably reduced in the animals having received the chelator. Liver and gut samples demonstrated unspecific inflammatory injury in both groups of animals. In summary, oxygen radical‐mediated tissue damage occurs rapidly following CLP‐induced sepsis. Based on histological and biochemical endpoints, treatment with the polymeric iron chelator, HES‐DFO, significantly attenuates systemic oxidant injury, the degree of protection being most impressive in the lung and kidney.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTThe effect of lipopolysaccharide (LPS) upon the cellular content of mRNA for several enzymes associated with the arachidonic acid cascade was determined in human microvessel‐derived endothelial cells. Cells were treated with either vehicle or 10 ng/mL LPS for up to 24 h. Reverse transcription followed by DNA amplification and Southern blotting were used to quantify mRNA for prostaglandin H synthase‐1, prostaglandin H synthase‐2, cytoplasmic PLAj, and a group II secretory PLA>. LPS treatment resulted in an increase in prostaglandin H synthase‐2 mRNA after 4 h with a second peak occurring at 12 h of incubation. The expression of prostaglandin H synthase‐1 mRNA was not altered by LPS treatment. An increase in cytoplasmic PLA2, mRNA but not group II PLA2, mRNA was seen after 12 h. These data demonstrate that LPS can increase mRNA production for the inducible form of prostaglandin H synthase and for cytoplasmic PLA2in a time‐dependent manner in human microvessel‐derived endothelial cells. These multiple, specific increases in the prostaglandin H synthase‐2 and phospholipase A2mRNA values suggest a complex interaction between bacterial LPS and the endothelial cell eicosanoid system.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTEndotoxins (lipopolysaccharides; LPS) are known to cause multiple organ failure, including renal dysfunction. The present report elucidates LPS distribution and effect on renal proximal tubules in an attempt to gain a better understanding of the cellular mechanism underlying the pathogenesis of renal dysfunction in endotoxemia and sepsis. Rats were intravenously treated with biotin‐linked or regularEscherichia coli(0111:B4) LPS (3 mg/kg) and sacrificed at different times. Kidneys were retrieved and examined for LPS localization, tubular permeability, ultracytochemical alterations, leukocyte sequestration, and ICAM‐1 expression. The functional impact of endotoxemia was also assessed by monitoring the changes in urine levels of glucose in timed collections up to 6 h. LPS was localized on the plasma membranes of the apical microvilli, the labyrinth of the lateral intercellular spaces, in various organelles of epithelial cells, and in the endothelial cells of the peritubular capillaries. LPS caused structural damage and calcium accumulation in the mitochondria, leakage of tight junctions, widening of the basolateral intercellular spaces, intracellular and extracellular edema, leukocyte margination and accumulation, vascular expression of ICAM‐1, and decrease of plasma membrane and mitochondrial Ca2+‐ATPase. Physiological study showed that both urine volume and glucose were greatly increased after LPS infusion. The pathological alterations in the proximal tubules may directly contribute to the reduction in the reabsorption ability of the proximal tubules.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ABSTRACTRat neonatal mortality to endotoxin and age‐related changes in adherent splenic cell mediator productionin vitrowere investigated. Neonatal rat pups, 24, 48, 96, and 216 h old or maternal adult rats were administered doses ofSalmonella enteritidisendotoxin, (.024 mg to 7.5 mg/kg) and survival was monitored for 72 h. Mortality demonstrated high sensitivity (p < .05) of neonates to endotoxin (particularly 24 h old neonates). Endotoxin administration (.6 mg/kg intracardiac) produced a 100% lethality in 24 h neonates (p < .05) versus 23% or less lethality in the 48 to 216 h old age group. Endotoxin administration (.4 mg/kg, subcutaneous) also produced 100% lethality in 24 h old neonates compared with reduced mortality versus older age groups. Endotoxinin vitrostimulated (p < .05) adherent splenic cell thromboxane (TX)B2, interleukin‐6, and nitrite production in most groups. Splenic cell nitrite production was higher (p < .05) in the 24 h old neonates, but lower in 48 h and 96 h old groups compared with maternal adults. Splenic cell TXB2, production was higher (p < .05) in the 24 h and 216 h old neonates relative to maternal adults. In conclusion, 24 h old rat pups are more susceptible to endotoxic shock than older age groups and adults, and exhibit altered production of the cellular mediators nitric oxide and TXB2.

ISSN:1073-2322    

出版商:OVID    

年代:1995

数据来源: OVID