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Topic:Endotoxin
Endotoxins are components of the outer membrane of Gram-negative bacteria that can have significant effects on horses when they enter the bloodstream. These molecules are known to trigger inflammatory responses in equine systems, leading to conditions such as endotoxemia, which can affect various physiological functions. Research on endotoxins in horses focuses on understanding their impact on equine health, the mechanisms of endotoxin-induced inflammation, and the potential therapeutic interventions. This page includes peer-reviewed research studies and scholarly articles that explore the biological effects, detection methods, and management strategies related to endotoxin exposure in horses.
Characterization of release of tumor necrosis factor, interleukin-1, and superoxide anion from equine white blood cells in response to endotoxin. Direct effects of endotoxin (lipopolysaccharide [LPS]) on equine WBC are known to stimulate the release of a variety of mediators including thromboxane, prostacyclin, and leukotrienes. In this study, 0.1 microgram of LPS/ml stimulated an early increase in tumor necrosis factor, succeeded by an increase in interleukin-1, but concentrations of LPS up to 5.0 micrograms/ml caused no significant increase in superoxide anion release. The concentration of LPS (0.1 microgram/ml) used in this experiment was in the range of concentrations measured in plasma of some horses with gastrointestinal problems....
Effect of hypertonic vs isotonic saline solution on responses to sublethal Escherichia coli endotoxemia in horses. Cardiovascular responses to sublethal endotoxin infusion (Escherichia coli, 50 micrograms/ml in lactated Ringer solution at 100 ml/h until pulmonary arterial pressure increased by 10 mm of Hg) were measured 2 times in 5 standing horses. In a 2-period crossover experimental design, horses were either administered hypertonic (2,400 mosm/kg of body weight, IV) or isotonic (300 mosm/kg, IV) NaCl solution after endotoxin challenges. Each solution was administered at a dose of 5 ml/kg (infusion rate, 80 ml/min). Complete data sets (mean arterial, central venous, and pulmonary arterial pressures, pul...
Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse. Using a modified bovine milk enzyme kinetic assay, xanthine oxidase activity of serum collected from 34 adult, healthy horses of both sexes was determined. Enzyme activity varied from 0 to 126 mU litre-1 with a mean of 44.95 +/- 21.05 mU litre-1. The optimal pH and temperature for maximal activity were 7.8 and 28 degrees C, respectively. Freezing the serum for four days at -70 degrees C did not destroy the enzyme activity. Various doses (25, 50 and 75 micrograms kg-1, intraperitoneally) of endotoxin (lipopolysaccharide D1 Escherichia coli O26:B6) previously known to have caused moderate to sev...
Hypoperfusion of the small intestine during slow infusion of a low dosage of endotoxin in anesthetized horses. The effects of intravenous infusion of endotoxin for 30 minutes at a cumulative dosage of 0.03 micrograms/kg on average carotid arterial pressure, and on average arterial pressure, capillary pressure, venous pressure, total vascular resistance, precapillary resistance, postcapillary resistance, and capillary filtration coefficient in the jejunum were compared to the effects of intravenous infusion of 0.9% sodium chloride solution in 6 anesthetized horses. Endotoxin significantly reduced intestinal venous blood flow by inducing vasoconstriction. Increased vascular resistance resulted from incre...
Endotoxin-induced tumor necrosis factor activity production by equine peritoneal macrophages. A study was performed to determine whether equine macrophages produce tumor necrosis factor (TNF) activity in vitro in response to endotoxin and to study the effects of endotoxin concentration and incubation time on the amount of TNF produced. Equine peritoneal macrophages were isolated and cultured in vitro for 2, 6, 12, or 24 hr in tissue culture media containing 1) no additive (nonstimulated control), 2) endotoxin (0.5 ng/ml, 5 ng/ml, or 5 micrograms/ml), or 3) the calcium ionophore A23187 (0.95 microM). The supernatant media concentrations of TNF activity were determined by an in vitro cyt...
Haemodynamic, pathological, haematological and behavioural changes during endotoxin infusion in equine neonates. The purpose of this study was to evaluate the effects of experimentally induced sublethal endotoxaemia in equine neonates. Four foals, between two and five days of age, were infused intravenously with 0.5 microgram/kg bodyweight of Salmonella typhimurium endotoxin (LPS) over a 5 h period. A four-day-old and a five-day-old foal, similarly infused with sterile isotonic saline, served as controls. Clinical signs were monitored, blood samples obtained for evaluation of selected haematological and biochemical parameters; and haemodynamic parameters were recorded hourly during the infusion, as well ...
[Clinical changes after intravenous administration of endotoxin in the horse]. The results of a study conducted to determine the clinical changes in 4 experimentally-induced cases of endotoxaemia in the horse are reported on. Endotoxaemia was induced by injecting commercially available E. coli 055:B5 lipopolysaccharide intravenously at a dose of 1 microgram kg-1. The parameters that were monitored include general behaviour, rectal temperature, heart rate, respiratory rate and quality, pulse quality, mucous membrane colour, capillary refill time, appearance of the faeces and the presence of laminitis. Increases in rectal temperature, respiratory and heart rate, capillary ...
[Clinico-pathological changes after intravenous administration of endotoxin in the horse]. The results of a study conducted to determine the clinico-pathological changes in 4 experimentally-induced cases of endotoxaemia in the horse are reported on. Endotoxaemia was induced by injecting commercially available E. coli 055:B5 lipopolysaccharide intravenously at a dose of 1 microgram kg-1. The haematocrit, red cell count, total and differential white cell counts, thrombocyte count, prothrombin time, partial thromboplastin time, fibrinogen level, level of fibrin degradation products, arterial acid-base status, serum lactate and blood glucose were determined repeatedly. Changes that occu...
Effect of dietary linolenic acid on endotoxin-induced thromboxane and prostacyclin production by equine peritoneal macrophages. In laboratory animals, the incorporation of alpha linolenic acid or other n-3 series fatty acids into the diet results in marked changes in cell membrane composition as well as arachidonic acid metabolism. The purpose of the present study was to determine whether endotoxin-induced thromboxane A2 (TxA2) and/or prostacyclin (PGI2) production by equine peritoneal macrophages was altered by feeding horses a diet containing 8% linseed oil as a source of alpha linolenic acid for 8 weeks. Peritoneal macrophages were cultured in vitro in the presence of endotoxin (LPS) (0.5-500 ng/ml) or calcium ionop...
Effects of polymyxin B on selected features of equine carbohydrate overload. Gram negative endotoxins play a contributory role in the syndrome which results from over consumption of carbohydrates by horses and ponies. Since the antibiotic polymyxin B exerts a direct anti-endotoxin effect by chemically modifying the active lipid A moiety of endotoxin, it might be expected to protect horses after carbohydrate overload and provide a new therapeutic and experimental tool for this condition. The present study was undertaken to evaluate the effect of polymyxin B on hemostatic, hemodynamic, acid-base, and clinical aspects of the syndrome resulting from carbohydrate overload. ...
Adverse effects of a proposed equine sublethal endotoxin model. Commercially available Escherichia coli 055: B5 lipopolysaccharide was administered intravenously experimentally at a dosage of 10 micrograms/kg to 2 horses. Various clinical and clinico-pathological parameters were monitored before and after the endotoxin administration. Because of a hopeless prognosis, and for humane reasons, euthanasia was applied on both horses 6 h after administration. Values recorded for the different parameters, including the blood lactate level, were consistent with a lethal condition. It would appear that an intravenous dose of 10 micrograms/kg of endotoxin is potenti...
Effects of allopurinol in experimental endotoxin shock in horses. The effect of allopurinol pretreatment 12 hours before an intraperitoneal challenge with a sublethal dose of Escherichia coli endotoxin (50 micrograms kg-1) was evaluated in 18 horses. The horses were divided among three equal groups: 1-endotoxin alone; 2-5 mg allopurinol kg-1 bodyweight plus endotoxin; and 3-50 mg allopurinol kg-1 bodyweight plus endotoxin. A variety of evaluation parameters were used. No differences among the groups were noted in rectal temperature, heart rate, respiration rate, haematological values, blood PaO2, blood PaCO2, blood pH or blood bicarbonate. Significant (P les...
Protection against clinical endotoxemia in horses by using plasma containing antibody to an Rc mutant E. coli (J5). Thirty-two horses with clinicopathologic evidence of endotoxic shock were randomly selected for a double-blind trial of hyperimmune lipopolysaccharide (LPS) core antigen plasma. Horses were suffering from acute toxic enteritis (n = 15), 360 degrees volvulus of the large colon (n = 9), proximal jejunitis/duodenitis (n = 6), or strangulating obstruction of the small intestine (n = 2). Plasma was harvested from suitable equine plasma donors (preimmune plasma) and horses were immunized with a whole-cell bacterin of an Rc mutant E. coli (J5). Plasma was again harvested from these horses when IgG EL...
Equine peritoneal macrophage production of thromboxane and prostacyclin in response to platelet activating factor and its receptor antagonist SRI 63-441. The formation of eicosanoids may be a primary route through which platelet activating factor (PAF) exerts its effects during endotoxemia. Since endotoxemia is a common cause of death in horses, a study was conducted to determine whether PAF could stimulate equine macrophage release of thromboxane A2 (TxA2) and prostacyclin (PGI2) and whether a PAF-receptor antagonist would alter macrophage eicosanoid synthesis. Equine peritoneal macrophages were cultured from clinically normal horses and exposed to various concentrations of PAF, the PAF-receptor antagonist SRI 63-441, endotoxin, or a combinati...
The effects of slow infusion of a low dosage of endotoxin in healthy horses. The effects of slow intravenous (i.v.) infusion of a very low dosage of endotoxin (a cumulative dosage of 0.03 microgram/kg bodyweight [bwt] infused over 60 mins) were evaluated in six conscious healthy horses. Duodenal, right ventral colon, and caecal contractions were detected with strain gauge force transducers. Lateral caecal arterial blood flow was measured using transit time ultrasonic blood flow probes. Duodenal contractile activity was not significantly altered by infusion of endotoxin. In contrast, the contractile activity of the right ventral colon 90 and 270 mins after infusion of e...
Plasma endotoxin concentrations in experimental and clinical equine subjects. Endotoxin (LPS) was quantitated in experimental subjects and in horses with naturally occurring gastrointestinal strangulation obstruction and/or septicaemic diseases to establish the fate of LPS and the clinical usefulness of the Limulus amoebocyte lysate (LAL) assay. The assay was validated for sensitivity (10 pg/ml), recovery (90 to 106 per cent), intra-assay precision (CV = 5.5 per cent) inter-assay precision (CV = 11 per cent), and stability of diluted, heat treated, frozen samples (at least 90 days). Plasma concentrations of LPS after sublethal (3 micrograms/kg) jugular or portal vein bo...
Antagonism of endotoxin-induced disruption of equine bowel motility by flunixin and phenylbutazone. Post operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre-treatment with intravenous (i.v.) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 microgram/kg bwt i.v. endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P < 0.01) for the stomach and left dorsal col...
In vitro reactivity of digital arteries and veins to vasoconstrictive mediators in healthy horses and in horses with early laminitis. The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norepinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the...
Endotoxin-induced procoagulant activity in equine peripheral blood monocytes. Increasing evidence has demonstrated the importance of monocyte procoagulant activity (PCA) in the pathogenesis of coagulopathies in a variety of diseases. Because endotoxin precipitated coagulopathies are common sequelae to intestinal ischemia/endotoxemia in the equine species, we investigated the ability of equine peripheral blood monocytes to express PCA. Monocytes isolated from five healthy adult horses were incubated in vitro with Escherichia coli endotoxin (10 micrograms), and the PCA was measured by the ability of cellular lysates to accelerate the clotting times of equine plasma in a m...
Detection of endotoxin in cases of equine colic. The Limulus amoebocyte lysate assay was used to test for the presence of endotoxin in 37 clinical cases of equine colic. Positive plasma titres were detected in 10 cases and the presence of endotoxin was significantly correlated with a high heart rate, a high packed cell volume and a poor prognosis. High levels of endotoxin were detected in gut contents taken from several sites in the gastrointestinal tract of normal horses.
Endotoxaemia in racehorses following exertion. Endotoxins (lipopolysaccharides-LPS) and anti-endotoxin IgG antibodies were measured in racehorses before and after races of 1,000, 2,000 and 2,800 m. Results show that the mean plasma concentration of endotoxin increased significantly (p less than 0.02) while the anti-LPS IgG concentration decreased significantly (p less than 0.005) in all horses following the races. Pre-race and post-race anti-LPS IgG levels in racing-fit racehorses were significantly higher than in untrained horses (p less than 0.05). The possibility therefore exists that training-induced stress leads to leakage of LPS into...
Ultrastructure of equine endothelial cells exposed to endotoxin and flunixin meglumine and equine neutrophils. An in vitro system of cultured equine endothelial cells was evaluated as a model for endotoxin (ET) exposure in the horse. Primary cell lines from pulmonary vessels and aortas were cultured from tissues of 6 horses. Effects of ET alone with and without serum and in combination with the cyclo-oxygenase inhibitor flunixin meglumine and isolated equine neutrophils were evaluated by transmission electron microscopy. Cells plus serum were incubated with 10, 25, 50, or 100 micrograms of ET/ml of incubation medium for 1, 3, 8, or 24 hours. Cells without serum were cultured for 1 and 3 hours. Flunixin...
Effects of a specific thromboxane synthetase inhibitor in equine endotoxaemia. Thromboxane A2 may play a major role in circulatory shock. In some species, thromboxane synthetase inhibitors have a beneficial effect on shock induced by endotoxin, trauma, sepsis and administration of arachidonate. In some shock models, however, results with thromboxane synthetase inhibitors have been conflicting. The effect of UK-38,485, a selective thromboxane inhibitor, was evaluated in ponies injected with endotoxin intraperitoneally. Four groups of ponies were used to compare the effects of endotoxin alone, UK-38,485 alone, treatment with UK-38,485 before endotoxin challenge and treatme...
Equine endotoxemia: cardiovascular, eicosanoid, hematologic, blood chemical, and plasma enzyme alterations. Ponies with electromagnetic blood flow transducers implanted around the main pulmonary and left main coronary arteries, were used to evaluate effects of chronic sublethal endotoxin on cardiac output (CO), stroke volume, and left coronary blood flow (LCBF). Plasma thromboxane (TX), as indicated by TXB2, prostacyclin as indicated by 6-keto-prostaglandin (PG) F1 alpha, and hematologic and blood chemical values also were evaluated. Over 24 hours, 2 groups of ponies were given progressively increasing IV and intraperitoneal doses of Escherichia coli lipopolysaccharide (LPS) at 0, 6, 12, and 18 hour...
Mixed venous oxygen tension as an estimate of cardiac output in anesthetized horses. The relationship between mixed venous O2 tension and cardiac output was studied in six anesthetized horses breathing 100% O2. Cardiac output, O2 consumption, mean arterial pressure, heart rate, and arterial and venous blood gases were measured after administration of xylazine or dobutamine to horses in lateral, sternal, and dorsal recumbencies. After approximately 3 hours, Escherichia coli endotoxin was administered while horses were in dorsal recumbency, and all measurements were repeated. Relationships between cardiac index (CI) and PVO2, heart rate, mean arterial pressure, jugular PVO2, and...
Effects of multiple low doses of flunixin meglumine on repeated endotoxin challenge in the horse. Previous work has shown repeated low doses of flunixin meglumine (FM) inhibit thromboxane production in normal horses. Enhanced concentrations of thromboxane in serum occurred after the drug therapy was discontinued. Our study was performed to evaluate the effects of low doses of FM in horses repeatedly challenged with endotoxin. Group I horses received E. coli endotoxin (0.1 microgram/kg IV) at 0 and 90 h. Group II horses received endotoxin and were also treated with FM (0.25 mg/kg IV) at 2, 10, 18, 26, 34, and 42 h after the initial administration of endotoxin. Clinical signs of endotoxemia ...
Low dose flunixin meglumine: effects on eicosanoid production and clinical signs induced by experimental endotoxaemia in horses. The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observe...
Effect of Salmonella typhimurium endotoxin on PGF-2 alpha release and fetal death in the mare. The infusion of Salmonella typhimurium endotoxin into pregnant mares resulted in a biphasic release pattern of PGF-2 alpha as determined by 15-keto-13,14-dihydro-PGF-2 alpha concentrations. The initial phase of 1 h duration was followed by accentuated release by 2 h after infusion; concentrations reached basal levels by 6 h. In 7 mares at 23, 26, 29, 33, 36, 53 and 55 days of gestation, fetal death occurred between 36 and 120 h after infusion; 12 mares at 46, 51, 56, 59, 65, 71, 73, 85, 103, 138, 283 and 318 days of gestation did not abort after endotoxin infusion. Luteal activity was compromi...
Endotoxin-induced hemodynamic and prostaglandin changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone. Shock was induced in four groups of anesthetized ponies with an intravenous injection of Escherichia coli endotoxin [125 micrograms/kg]. Five minutes after endotoxin injection, the ponies were given no treatment (group A), flunixin meglumine (FM:1.1 mg/kg) (group B), dexamethasone (2 mg/kg) (group C), or prednisolone (10 mg/kg) (group D). Additionally, FM was given every 3 hours, and the steroids were given at 3, 9, and 24 hours following endotoxin. Hemodynamic measurements were made during the 4-hour anesthetic period. Blood samples were collected for the analysis of prostaglandins, blood che...
Plasma endotoxin levels in horses subjected to carbohydrate induced laminitis. Thirteen (65 per cent) of 20 horses subjected to carbohydrate overload developed Obel Grade 3 lameness within 56 h. Increases in plasma endotoxin from control levels of less than 0.1 ng/litre to values ranging from 2.4 to 81.53 ng/litre were measured in 11 (85 per cent) of 13 horses during the onset of Obel Grade 3 lameness. Obel Grade 3 lameness was associated with rises in plasma Gram-negative endotoxin levels in 11 (92 per cent) of 12 horses. Two peak increases separated by 16 h were verified in five (45 per cent) of 11 horses that exhibited both endotoxaemia and Obel Grade 3 lameness. The ...
