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1.
The purpose of this study was to assess whether polymyxin B together with pentoxifylline, had beneficial effects on the acute-phase-response to E. coli endotoxin in the dwarf goat ( n  = 6). Polymyxin B partly neutralizes E. coli endotoxin by forming inactive polymyxin B-lipopolysaccharide (LPS) complexes; pentoxifylline has been reported to suppress the LPS-induced production of tumour necrosis factor (TNF-α). E. coli LPS (0.0067 μg/kg/min over 30 min) induced fever, tachycardia, inhibition of rumen motility, a decline in WBC, lymphopenia, and decreases in plasma zinc and iron concentrations. Most of the haematological, blood biochemical and clinical effects of E. coli LPS were significantly reduced by polymyxin B pretreatment (0.1 mg/kg/min over 30 min, i.v.). Pentoxifylline (0.3 mg/kg/min over 30 min, i.v.) did not reduce the clinical and blood biochemical effects of E. coli LPS, however, it modulated the number of circulating neutrophils. No synergistic effects were observed after i.v. infusion of polymyxin B with pentoxifylline. The lack of synergy may be due to the production and release of pro-inflammatory cytokines other than TNF-α.  相似文献   

2.
The antipyretic efficacy of meloxicam was evaluated in a feline endotoxin model using a replicated change-over design. Twelve adult cats of both sexes were allocated at random to three experimental groups. At 30 min prior to the intravenous (i.v.) endotoxin challenge (0.5 µg/kg body weight(b.w.)), 2 animals in each group received an i.v. injection of 0.1, 0.3 or 0.5 mg meloxicam/kg b.w. and the two remaining animals in each group received physiological saline. In a second phase, 21 days later, the meloxicam/placebo treatment was exchanged within each group. The rectal temperature and scores for general demeanour were determined at 30-min intervals from before dosing to 300 min after the endotoxin challenge. Haematological parameters were analysed before and 60 min after administration of endotoxin. The results indicated a significant dose-dependent antipyretic response to meloxicam after endotoxin challenge. The antipyretic response in the medium- and high-dose meloxicam groups did not differ significantly, but both were significantly different from the low-dosage group. The individual effects of endotoxin on general demeanour were rather variable but meloxicam tended to have a beneficial effect. Endotoxin induced a reduction in the white blood cell count but this was not influenced by meloxicam. It was concluded that the pyretic endotoxin model is very suitable for studying new NSAIDs in cats and that the optimum single dose of meloxicam in this model was 0.3 mg/kg b.w.Abbreviations AUC area under the curve - b.w. body weight - i.v. intravenous - LPS lipopolysaccharide - MCV mean corpuscular volume - NSAID non-steroidal anti-inflammatory drug - WBC white blood cell count  相似文献   

3.
In conscious pigs the influence of intravenous infusion of live E. coli (7×108/kg), of the equivalent amount of endotoxin (20 g/kg) or of a high dose of endotoxin (2.5 mg/kg) on the hemodynamic, clinical and pathological parameters and on survival rate was studied. E. coli and endotoxin infusion resulted in pulmonary hypertension, systemic arterial hypotension, a decrease in cardiac output and an increase in heart rate. Clinical signs were characterized by respiratory and nervous disturbances, whereas necropsy revealed hemorrhages and edema in several organs. Although these findings were similar in the three groups, a marked difference in lethality was observed. Infusion of E. coli or of the high dose of endotoxin resulted in a significant mortality, whereas all pigs survived the infusion of the low dose of endotoxin. This suggests that the lethal pathophysiological mechanisms may only become activated when a sufficient amount of endotoxin is released into the circulation.  相似文献   

4.
An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 g/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The steength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V, 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.Abbreviations BP blood pressure - CO cardiac output - LPS lipopolysaccharides - Glib glibenclamide - i.m. intramuscular - i.v. intravenous - SEM standard error of the mean - v/v volume/volume P ab, abdominal pressure - P di transdiaphragmatic pressure - P oes oesophageal pressure  相似文献   

5.
Summary

The most common sign of febrile diseases is anorexia, which develops at a time when adequate caloric and micronutrient availability may be critical. In order to study the relationship of fever and anorexia, feed intake in dwarf goats was studied under conditions of fever and antipyresis. Furthermore, experiments were done to establish whether a feed intake stimulant would override the anorexia during febrile conditions. Infection with Ehrlichia phagocytophila and i.v. injection of Escherichia coli endotoxin (0111B4, 0.1 μg/kg body weight) both resulted in increased rectal temperatures and significant reductions in feed intake. Administration of the antipyretic drug flurbiprofen (1 mg/kg) to febrile animals inhibited the temperature responses, but food intake was still suppressed. Diazepam (0.06 mg/kg), a feed intake stimulant, did not override the anorexia associated with fever. Blocking the febrile response of E. coli LPS‐injected goats with flurbiprofen plus diazepam or with flurbiprofen plus naloxone (0.1 mg/kg) did not antagonise their reduced feed intake either.

The effects of these drugs and of endotoxin on rumen motility adds an interesting aspect to their activities in the CNS, since the CNS has been shown to regulate various aspects of forestomach motility, which in turn could alter feeding behaviour. Moreover, our findings are consistent with the hypothesis that the suppression of feed intake might depend on the release of interleukin‐1.  相似文献   

6.
Summary

ACTH (μg kg ‐1 i.v.) and prednisolone (1 μg‐1 i.v.) caused a moderate but statistically significant inhibition of rumen contractions, whereas no effects on heart rate and body temperature were observed. Both hormones induced hyperglycaemia and leucocytosis, characterised by moderate lymphopenia and a profound increase in the number of circulating neutrophils. A significant decrease in plasma iron and increase in plasma zinc concentrations were observed.

After 3 daily i.m. injections of ACTH (10 μg ‐1 day ‐1) decreases were seen in both serum Alkaline phosphatase (ALP) activity and plasma trace metal concentrations; heart rate was significantly higher. Intraveneous injection of E. coli endotoxin (0.1 μg kg ‐1) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophilic leucocytosis, hypoferraemia, hypozincaemia, hypoglycaemia and a decline in serum ALP activity. ACTH, given for 3 days, reduced the febrile responses to E. coli endotoxin, modified the changes in heart rate, intensified the inhibition of rumen contractions, and induced a more marked decrease in the number of circulating neutrophils. ACTH pretreatment did not affect the endotoxin‐induced decrease in blood glucose concentrations nor the drop in plasma zinc and iron values.

These results suggest that (1) glucocorticosteroids are not primarily involved in the fall in plasma iron and zinc concentrations during E. coli endotoxin‐induced fever, (2) the effects of endotoxin released glucocorticosteroids on white blood cells and blood glucose are masked by some other effect(s) of endotoxin, and (3) in dwarf goats, ACTH has antipyretic properties without influencing normal body temperature. This effect is probably not dependent on adrenal cortical activity.  相似文献   

7.
Reasons for performing study: Insulin resistance (IR) is a risk factor for pasture‐associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin‐resistant horses requires further study. Hypothesis: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n = 24) were divided into 3 groups. A lipopolysaccharide (LPS; n = 8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate infusion, an oligofructose (OF; n = 8) group that received an infusion of saline followed by 5 g/kg bwt OF via nasogastric intubation, and a LPS/OF (n = 8) group that received LPS followed 16 h later by OF. Glucose and insulin dynamics were evaluated at ‐24 h and 48 h using the frequently sampled i.v. glucose tolerance test and minimal model analysis. Physical examinations and haematology were performed and the severity of laminitis assessed. Results: Horses receiving LPS developed leucopenia and both LPS and OF induced clinical signs consistent with systemic inflammation. Insulin sensitivity significantly decreased (P<0.001) over time, but responses did not differ significantly among groups. Time (P<0.001) and treatment × time (P = 0.038) effects were detected for the acute insulin response to glucose, with mean values significantly increasing in LPS and LPS/OF groups, but not the OF group. Five horses in the LPS/OF group developed clinical laminitis compared with 0 and 2 horses in the LPS and OF groups, respectively. Conclusions: Endotoxaemia and carbohydrate overload reduce insulin sensitivity in horses. Endotoxin pretreatment does not affect the alterations in glucose metabolism induced by carbohydrate overload. Potential relevance: Insulin sensitivity decreases after carbohydrate overload in horses, which may be relevant to the development of pasture‐associated laminitis.  相似文献   

8.
1. The effect of endotoxin, interleukin‐1β and prostaglandin on fever response was studied in 80 broilers (Hubbard strain). Endotoxin (E. coli, LPS) was injected iv (1.5 μg/kg) and icv (1.5 μg/bird); interleukin‐1 (human recombinant IL‐1β, 80 pg/bird) and prostaglandin E2 (5 μg/bird) were injected icv. Indomethacin (10 mg/kg, iv) pretreatment was also used before iv endotoxin injection.

2. The results showed that indomethacin was able to block the fever response induced by iv endotoxin injection, and IL‐1β and PGE2 were both effective in producing fever when injected icv. These data suggest a prostaglandin‐mediated fever response by broilers, and also a strong evidence of the involvement of endogenous pyrogen (interleukin‐1) in fever response in birds.  相似文献   


9.
A new experimental model forin vivo studies on local inflammation in the goat is presented. The teat and udder cisterns were separated by a surgical procedure, resulting in the teat cistern being an isolated pouch which is easily accessible through the teat canal and suitable for experimental studies. The surgery was consistently successful in closing the passage and no post-surgical complications were observed.The model was applied to a study of the inflammatory response induced by infusion ofSalmonella endotoxin. A marked response was observed as measured by the accumulation of leukocytes, serum albumin andN-acetyl--d-glucosaminidase (NAGase) in the test cistern. An initial increase in serum albumin, indicating an increase in the epithelial permeability, was observed from 1.5 h after endotoxin infusion. Approximately 0.5 h later, the cell count started to increase, reaching its peak level 3 h after infusion. The NAGase concentration was closely correlated with the cell count.The model provides new possibilities forin vivo studies on local inflammation and fulfils many of the requirements of an inflammatory model; for example, it allows non-traumatic repeated samplings from the same animal. The goat is a suitable experimental animal for many studies and, as each goat has two teats, intra-goat comparisons can be performeed.Abbreviations LPS lipopolysaccharide - FreeNAG NAGase in cell-free sample - NAGase N-acetyl--d-glucosaminidase; saline, sterile 0.9% (w/v) NaCl - TotNAG NAGase in cell-containing samples  相似文献   

10.
Sheep were subjected to immune challenge with either recombinant human interleukin-6 (rhIL-6; 2.0 μg/kg; n = 5), Escherichia coli lipopolysaccharide (LPS) endotoxin (400 ng/kg; n = 7), or saline (n = 6) to determine if IL-6 activates the febrile and hypothalamic-pituitary-adrenal axis (HPAA) responses in sheep, and to compare these responses with those associated with endotoxemia. Blood was collected over time to measure plasma adrenocorticotropic hormone (ACTH) and serum cortisol concentrations as indicators of HPAA activity. Unlike LPS, rhIL-6 was not pyrogenic in sheep at this challenge dose. In contrast, rhIL-6 elicited ACTH and cortisol responses that peaked earlier than those induced by LPS. These results suggest that this dose of IL-6, alone, is not sufficient to elicit the febrile response in sheep, however, it is a potent activator of the ovine HPAA response.  相似文献   

11.
Four clinically normal stallions were infused intravenously with endotoxin (LPS) from Escherichia coli 055:B5 at a dose of 0.3 microg/kg b.w. and four stallions were treated with flunixin meglumine (FM) as a single intravenous injection at a dose of 1.1 mg/kg b.w., 5 min after the infusion of LPS. In response to endotoxin infusion, stallions' reaction was fever (increased rectal and scrotal skin temperature), increased heart rate (HR) and leucopenia. Administration of endotoxin also influenced the level of testosterone (decrease at 3-24 h and increase at 48-72 h after LPS administration) in the blood serum. FM treatment prevented an endotoxin-induced increase in rectal and scrotal skin temperature, HR, with no influence on the decrease of leucocytes. Administration of FM only had a significant effect on the latter changes (at 24-72 h) of serum testosterone concentration after addition of endotoxin.  相似文献   

12.
The kinetic profiles of norfloxacin were evaluated in afebrile, febrile and probenecid pre-treated (70 mg/kg orally) febrile goats after a single intravenous (i.v) dose (5 mg/kg). Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.2 g/kg, i.v.) and repeating it in half the dose (0.1 g/kg) 5 h later. The plasma pharmacokinetic values for norfloxacin were best represented using a two-compartment open model. The peak norfloxacin plasma level of 90.52±3.18 g/ml attained in the probenecid pre-treated febrile goats was higher than that in the febrile (75.46±0.72 g/ml) or afebrile goats (62.25±1.23 g/ml). ClB and K el values were significantly (p<0.01) decreased in febrile compared with afebrile goats. These values were further reduced in febrile goats after probenecid pre-treatment. However, t 1/2 was not affected by the fever-probenecid interaction. Norfloxacin may be used as an infusion with probenecid in caprine diseases where very high plasma levels are required to combat resistant organisms such as Bacteroides.Abbreviations MIC minimum inhibitory concentration - LPS lipopolysaccharide - i.v. intravenous(ly)  相似文献   

13.
Local and systemic activation of coagulation is frequently associated with bacterial sepsis. The coagulopathy is due, at least in part, to expression of tissue factor (TF) by monocytes and macrophages. The purpose of this study was to evaluate the expression of procoagulant activity by bovine alveolar macrophages, leukocytes and platelets, and to determine the relative potency of three chemical inhibitors of TF expression (pentoxifylline, retinoic acid, and cyclosporin A). Bovine alveolar macrophages were stimulated with lipopolysaccharide (LPS) derived from Pasteurella haemolytica or recombinant bovine tumour nervous factor (TNF) and dose- and time-dependent effects on TF expression were studied. LPS and TNF induced TF expression in alveolar macrophages and LPS treatment of whole blood induced TF expression in mononuclear cells. Neutrophils and platelets also expressed procoagulant activity, but this activity was not inhibited by anti-bovine TF monoclonal antibody. Pentoxifylline (40 mol/L), retinoic acid (0.01 mmol/L) and cyclosporin A (0.08 mol/L) inhibited TF expression when added concurrently with LPS or TNF, but not when added 4 h after stimulation. TF mRNA was not detected in unstimulated alveolar macrophages by Northern blot analysis. In contrast, exposure to LPS or TNF for 6 h induced marked expression of TF mRNA, which was inhibited by treatment with pentoxifylline, retinoic acid and cyclosporin A. Expression of TNF by alveolar macrophages stimulated with LPS was also inhibited by these compounds. Our results indicate that procoagulant activity expressed by alveolar macrophages and monocytes is associated with expression of TF, whereas procoagulant activity expressed by neutrophils and platelets is not. The concentrations of pentoxifylline and retinoic acid necessary for inhibition of TF expression in vitro may not be achievable in vivo owing to their toxic effects. However, the in vitro concentration of cyclosporin A that inhibited TF expression did not exceed the plasma concentration observed in humans, and therefore may be useful for inhibition of TF expression in vivo.Abbreviations BAL bronchoalveolar lavage - LPS lipopolysaccharide - cDNA cloned deoxyribonucleic acid - cAMP cyclic adenosine monophosphate - GAPDH glyceraldehyde phosphate dehydrogenase - mRNA messenger ribonucleic acid - TF tissue factor - TNF tumour necrosis factor - DPBS Dulbecco's phosphate-buffered saline  相似文献   

14.
将22只山羊随机分为5组，即对照组、内毒素血症模型组（内毒素LPS1800EU／kg）、内毒素血症氨基胍组（AG25mg／kg）、大剂量内毒素血症模型组（内毒素LPS5400EU／kg）和大剂量内毒素血症氨基胍组。肉眼观察动物精神状态和粪便的变化；用体温计检测直肠体温；用听诊器记录呼吸频率。结果表明：实验后1～9h，大、小剂量的内毒素（LPS）均使山羊表现出不同程度的精神不振、腹泻、食欲废绝。体温显著升高（P〈0．05），24h后体温恢复正常（P〉0．05）；但氨基胍对内毒素血症时体温的变化无调理作用（P〉0．05）。小剂量LPS和氨基胍对呼吸频率无影响（P〉0．05）；大剂量LPS却显著增加了山羊呼吸频率（P〈0．05），同时氨基胍也显著阻止了呼吸频率的升高（P〈0．05）。揭示体温、呼吸与内毒素剂量存在依赖关系；小剂量的氨基胍（25mg／kg）对内毒素血症时体温变化没有影响，但可明显减少呼吸频率。  相似文献   

15.
Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.BoTNF-alpha, r.HuTNF-alpha and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF-alpha.  相似文献   

16.
OBJECTIVE: To evaluate systemic effects of i.v. infusion of ATP-MgCl2 subsequent to infusion of a low dose of endotoxin in horses. ANIMALS: 12 adult horses. PROCEDURE: Horses were administered endotoxin (lipopolysaccharide [LPS]) or saline (0.9% NaCl) solution i.v., during a 30-minute period. Immediately thereafter, horses in each group were infused i.v. with ATP-MgCl2 or saline solution. Two weeks later, horses were administered the opposite solution (LPS or saline solution), but it was followed by the same infusion as 2 weeks previously (ie, ATP-MgCl2 or saline solution). Cardiopulmonary and clinicopathologic variables, cytokine activity, and endothelin (ET) concentrations were recorded. RESULTS: IV infusion of ATP-MgCl2 after administration of a low dose of endotoxin failed to attenuate the cardiopulmonary, clinicopathologic, and cytokine alterations that develop secondary to endotoxin exposure. The combination of LPS and ATP-MgCl2 potentiated pulmonary hypertension, leukopenia, and neutropenia when compared with the combination of LPS and saline solution. The combination of LPS and ATP-MgCl2 resulted in thrombocytopenia. Endothelin concentration was increased in jugular venous and pulmonary arterial plasma in horses receiving LPS and ATP-MgCl2. Similar increases were not observed with LPS and saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ATP-MgCl2 did not protect horses from systemic effects of experimentally induced endotoxemia. Furthermore, the use of ATP-MgCl2 during endotoxemia may worsen the cardiopulmonary and clinicopathologic status of affected horses. Because ATP and other adenine nucleotides are released from cells during shock, their potential role in the development of hemodynamic derangements, leukocyte adherence, and coagulopathies during endotoxemic episodes warrants further investigation.  相似文献   

17.
REASONS FOR PERFORMING STUDY: Endotoxaemia is one of the most severe and ubiquitous disease processes in horses. Although dimethyl sulphoxide (DMSO) is used clinically in horses, there is no study indicating its efficacy in endotoxaemic horses. HYPOTHESIS: DMSO ameliorates the clinical response to i.v. lipopolysaccharide (LPS) administration. METHODS: Eighteen horses were assigned randomly to one of 4 groups: Normosol-LPS (0.2 mug/kg bwt, i.v.); DMSO (1 g/kg bwt, i.v.)-saline; high-dose DMSO (1 g/kg bwt, i.v.)LPS; low-dose DMSO (20 mg/kg bwt, i.v.)-LPS. Horses participating in the DMSO-saline group were later assigned randomly to one of the LPS groups. Data for physical parameters, white blood cell counts, plasma TNF-alpha, and blood lactate and glucose concentrations were examined for the effect of treatment using a repeated-measures mixed-model ANOVA. A value of P<0.05 was considered significant. RESULTS: Endotoxaemia occurred in all horses receiving LPS, as indicated by the clinical score, physical parameters, haemoconcentration and leucopenia. High-dose DMSO ameliorated the effect of LPS on fever. DMSO, at either dose, but did not have a significant effect on LPS-induced changes in all other evaluated parameters. CONCLUSIONS: In this study, DMSO had minimal effects on clinical signs of induced endotoxaemia in horses. The effects were manifested by amelioration of LPS-induced fever.  相似文献   

18.
The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at ?24, ?16, and ?0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non‐compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half‐life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day?1 ml?1), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.  相似文献   

19.
The interaction between constitutive nitric oxide and oxygen may depend on the degree of tissue oxygenation and may play a critical role in the pathophysiological response to endotoxaemia. We investigated if hyperoxia (100% O2) attenuated the systemic and pulmonary vasoconstriction and increased biosynthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin (PG) F1α induced by inhibition of nitric oxide synthase with NG-nitro-l -arginine-methyl-ester (L-NAME) in a porcine model of endotoxaemia. Twenty-two domestic, random source pigs, weighing 15.4 ± 2.7 kg (mean ± standard deviation) were the subjects of this study. Pigs were anaesthetized with isoflurane in 100% O2, orotracheally intubated and ventilated to maintain normocapnia, and then instrumented for haemodynamic monitoring. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O2 (Control, n = 6); Escherichia coli lipopolysaccharide (5 μg/kg/h from 1 to 2 h followed by 2 μg/kg/h from 2 to 5 h) + 30% O2 (LPS, n = 4); L-NAME (0.5 mg/kg/h, from 0 to 5 h) + LPS + 100% O2 (n = 6); and L-NAME + LPS + 30% O2 (n = 6). L-NAME and endotoxin significantly (P < 0.05) increased mean arterial pressure, mean pulmonary arterial pressure, and systemic and pulmonary vascular resistance index beginning at 90 min. When results were pooled across all time periods, mean arterial pressure and mean pulmonary arterial pressure were significantly higher in the L-NAME + LPS + 30% O2 group than all other groups, reflecting pulmonary and systemic vasoconstriction. Hyperoxia attenuated the L-NAME + LPS-induced increases in TXB2 and 6-keto-PGF1α concentrations at 90 and 120 min and 120 min, respectively, although the differences were not statistically significant. These results support the observation that nitric oxide synthase inhibition with L-NAME has deleterious haemodynamic effects in this model of endotoxaemia. The temporal attenuation of L-NAME-induced pulmonary and systemic vasoconstriction by hyperoxia suggested that the haemodynamic effects of acute endotoxaemia were in part influenced by the relative amounts of nitric oxide and oxygen present.  相似文献   

20.
Endotoxemia is an important cause of morbidity and mortality in the neonate. Although many models are used to study the problem, none completely simulates the natural disease. To more clearly define a bovine neonatal endotoxemia model we studied the effects of dose of endotoxin on clinical, hematological and biochemical variables. Thirty-four neonatal calves were administered Escherichia coli endotoxin (LPS) at 0 (0.9% saline solution), 0.2, 2.0 or 20 micrograms/kg, by either IV bolus or infusion over 50 minutes. Variables monitored included mean arterial blood pressure (MAP), leukocyte (WBC) count, plasma glucose and lactate concentrations and clinical status. All LPS-treated calves displayed similar clinical signs within one hour. Dose-dependent differences in response to LPS among groups became evident over time. Substantial dose-dependent changes in attitude, appetite, mucous membrane character, capillary refill time, MAP, plasma glucose and lactate concentrations, and WBC count were noted in LPS-treated calves. Higher doses of LPS induced a more prolonged clinical response and significantly (p < 0.05) greater hypotension, lacticemia and hypoglycemia. While dose altered the response to endotoxin, the method of administration had no overall effect on the variables measured.  相似文献   

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