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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.
Alterations in serum parathyroid hormone and electrolyte concentrations and urinary excretion of electrolytes in horses with induced endotoxemia. Hypocalcemia and hypomagnesemia are common in horses with sepsis and endotoxemia. We hypothesize that endotoxemia triggers a systemic inflammatory response that results in hypocalcemia and hypomagnesemia. The goal of this study was to determine the effect of endotoxin (lipopolysaccharide [LPS]) administration to healthy horses on serum parathyroid hormone (PTH), ionized calcium (Ca2+) and total calcium (tCa), ionized magnesium (Mg2+) and total magnesium (tMg), phosphate (Pi), potassium (K+), sodium (Na+), chloride (Cl-), and insulin concentrations, and on the urinary excretion of these electro...
Effect of acute sublethal endotoxaemia on in vitro digital vascular reactivity in horses. Endotoxaemia is a syndrome linked to the development of equine laminitis; however, the relationship between them is uncertain. The aim of this experiment was to evaluate the effect of an experimental acute sublethal endotoxaemia model on in vitro equine palmar digital vascular reactivity. Rings of arteries and veins of each forelimb were obtained from 11 clinically healthy horses submitted to two surgical procedures, 3 weeks apart. Before the second surgery, 0.25 microg/kg of lipopolysaccharide from Escherichia coli O55:B5 in saline, was administered i.v. in 30 min. After 3 h, the vessels were...
Polymyxin B protects horses against induced endotoxaemia in vivo. A safe, affordable and effective treatment for endotoxaemia in horses is needed in order to reduce the incidence of this potentially fatal condition. Objective: To evaluate the effect of polymyxin B (PMB) on signs of experimentally-induced endotoxaemia. Objective: PMB ameliorates the adverse effects of endotoxaemia without causing nephrotoxicity. Methods: Four groups of 6 healthy mature horses each received 20 ng endotoxin/kg bwt i.v. over 30 mins. Additionally, each group received one of the following i.v.; 5000 u PMB/kg bwt 30 mins before endotoxin infusion; 5000 u PMB/kg bwt 30 mins after e...
Endotoxin-induced digital vasoconstriction in horses: associated changes in plasma concentrations of vasoconstrictor mediators. Lipopolysaccharide (LPS) infusion reduces digital perfusion, but the mediators responsible remain undetermined. Objective: To identify vasoconstrictor mediators released following LPS infusion and relate their appearance in plasma to digital blood flow alterations. Methods: Blood flow in the lateral digital vessels of 6 Thoroughbred horses, following a 30 min infusion of LPS (E. coli 055:B5; 30 ng/kg), was measured using Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures (HWST and CBST) were made. Serial blood samples were collected and plasma...
Postoperative management of the large colon volvulus patient. Horses with large colon volvulus (LCV) often require intensive postoperative medical management. Although early referral and surgical intervention are critical for minimal postoperative complications and a successful outcome, this is often not possible for many reasons. Endotoxemia, extensive mucosal damage with subsequent severe hypoproteinemia, and focal ischemic necrosis are the major causes of postoperative morbidity and mortality. Although fluid therapy, flunixin meglumine, and antimicrobials are still the mainstay of perioperative management, synthetic colloids are being used to maintain...
Plasma endotoxin concentration in horses: a methods study. Accurate determination of plasma endotoxin concentration is critical for ex vivo and in vitro cellular and molecular studies of endotoxemia in horses. However, reports are conflicting with respect to anticoagulant, handling, and sample preparation. Objective: The purpose of this study was to determine the effect of blood sample fraction and handling time on measurement of endotoxin concentration in horses. Methods: Whole blood, anticoagulated with 3.8% (0.12 M) sodium citrate (9:1), was collected from 5 healthy horses. Whole blood (WB), platelet-rich plasma (PRP), and platelet-poor plasma (PPP...
Effects of infusion of adenosine triphosphate-magnesium chloride on cardiopulmonary and clinicopathologic variables, cytokine activity, and endothelin concentration in horses administered a low dose of endotoxin. To evaluate systemic effects of i.v. infusion of ATP-MgCl2 subsequent to infusion of a low dose of endotoxin in horses. Methods: 12 adult horses. Methods: 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 clinicopatho...
Treatment of endotoxemia. Although recognition of clinical signs of endotoxemia is not difficult, determining the underlying cause for the development of endotoxemia may be a challenging task. For this reason, importance must be placed on performance of a thorough physical examination, attention to detail, and determination of whether or not surgical intervention is required. In most instances, a definitive diagnosis may require repeated examinations and laboratory work. In the meantime, affected animals require treatment for endotoxemia, with the aim being to reduce the duration of endotoxemia, prevent the interaction...
Arterionecrosis of the equine mesentery in naturally occurring endotoxaemia. This report describes the mesenteric arteriolar lesions in a Thoroughbred racehorse with endotoxaemia due to colic. The vascular lesions consisted of a striking loss of medial smooth muscle cells, associated with granular cell debris derived from necrosed muscle cells, plasma insudation, erythrocyte infiltration and the deposition of a fibrinoid substance (fibrinoid degeneration) in the entire arterial wall, possibly produced by the infiltration of blood components through endothelial cell junctions into the arterial wall. The morphology of the mesenteric arteriolar necrosis closely resembled ...
Effect of induced unilateral synovitis of distal intertarsal and tarsometatarsal joints on sagittal plane kinematics and kinetics of trotting horses. To study the effect of unilateral synovitis in the distal intertarsal and tarsometatarsal joints on locomotion, including the compensating effects within and between limbs. Methods: 4 clinically normal horses. Methods: Gait analyses including kinematics, force plate, and inverse dynamic analysis were performed at the trot before lameness, after which synovitis was induced by injecting endotoxin into the right distal intertarsal and tarsometatarsal joints. Gait analyses were repeated 24 to 30 hours later during lameness. Differences between the stride variables during the 2 conditions (lame and...
A retrospective analysis of hepatic injury in horses with proximal enteritis (1984-2002). The purpose of this study was to test the hypothesis that horses with proximal enteritis (PE) are predisposed to hepatic injury. We also determined whether the presence of liver injury in horses with PE was associated with other clinicopathologic abnormalities or affected outcome. The medical records of all horses admitted for evaluation of colic and gastric reflux between 1984 and 2002 were reviewed. Horses were considered to have PE if the diagnosis was made at surgery or postmortem examination or if they had clinical findings consistent with PE. Horses with a small intestinal strangulating ...
Platelets enhance endotoxin-induced monocyte tissue factor (TF) activity in the horse. Endotoxaemia is the leading cause of death in horses. Disseminated intravascular coagulation (DIG), stimulated by induced monocyte proteins, is a prominent feature. Monocyte-platelet cellular interactions are central to the vascular dysfunction produced by circulating endotoxin and are implicated in many thrombotic diseases in the horse. This study reports that endotoxin (0.01-10 microg ml(-1)) and blood platelets (2.5 x 10(7) - 1 x 10(8) ml(-1)) are potent inducers of expression and activity of monocyte tissue factor (TF), the primary activator of the blood coagulation protease cascade. The c...
Evaluation of in vitro properties of di-tri-octahedral smectite on clostridial toxins and growth. Clostridial colitis and endotoxaemia of intestinal origin are significant causes of morbidity and mortality in horses. Intestinal adsorbents are available for treatment of these conditions; however, little information exists supporting their use. Objective: To evaluate the ability of di-tri-octahedral smectite to bind to Clostridium difficile toxins A and B, C. perfringens enterotoxin and endotoxin, inhibit clostridial growth and the actions of metronidazole in vitro. Methods: Clostridium difficile toxins, C. perfringens enterotoxin and endotoxin were mixed with serial dilutions of di-tri-octa...
Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses. Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. Objective: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction....
Flow cytometric analysis of peripheral blood mononuclear cells induced by experimental endotoxemia in horse. Cellular activation and functional cell surface markers were evaluated during experimentally-induced endotoxemia in healthy horses. Eight healthy adult horses were infused a low dose of endotoxin (lipopolysaccharide from Escherichia coli O26: B6, 30 ng/kg of body weight, IV) and five control horses were given an equivalent volume of sterile saline solution. Venous blood samples were collected for flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and to measure plasma endotoxin concentrations. Clinical signs of endotoxemia were recorded at 10, 20, 30, 40, 50 min, 1, 2, 3, 4...
Lipopolysaccharide and interferon gamma activate nuclear factor kappa B and induce cyclo-oxygenase-2 in equine vascular smooth muscle cells. Equine endotoxaemia is an important cause of morbidity and mortality in horses caused by the interaction of bacterial lipopolysaccharide (LPS) with cells such as macrophages and vascular smooth muscle. In this study we isolated equine vascular smooth muscle from a variety of vessels and stimulated it with LPS and human interferon (hIFN)-gamma. Using reverse transcriptase polymerase chain reaction (rt-PCR) and Western blot analysis we show that cyclooxygenase-2 (COX-2) is readily expressed in equine vascular smooth muscle. Vascular smooth muscle cells produced prostaglandin E2 in response to LP...
Effects of lipopolysaccharide and phenylbutazone on gastric contents in the horse. Endotoxaemia causes a disruption of gastrointestinal motility in the horse but there is no information on its effects on gastric secretion. Lipopolysaccharide (LPS) administration is known to affect gastric secretion in other species. Objective: That LPS, a toxic component of Gram-negative bacteria, would reduce gastric acid secretion and that pretreatment with phenylbutazone (PBZ) would block the effects of LPS. Methods: The effects of LPS and PBZ on gastric contents were investigated in fasted, mature horses, with permanent gastric cannulae. Horses were pretreated with either saline or PBZ 1...
Effects on plasma endotoxin and eicosanoid concentrations and serum cytokine activities in horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions. To determine plasma endotoxin concentration in horses competing in a 48-, 83-, or 159-km endurance race and its importance with regard to physical, hematologic, or serum and plasma biochemical variables. Methods: 3 horses. Methods: Weight and rectal temperature measurements and blood samples were obtained before, during, and after exercise. Blood samples were analyzed for plasma endotoxin concentration; serum antiendotoxin antibody titers; thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (PGF1alpha) concentrations; tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) activitie...
Evaluation of beta3-adrenoceptor-mediated relaxation in intact and endotoxin-treated equine digital veins. To investigate the functional expression of beta3-adrenoceptors (beta3-ARs) in equine digital veins (EDVs) and to examine whether beta3-AR relaxation was altered in EDVs incubated with endotoxin. Methods: Forelimbs obtained from 30 horses. Methods: Forelimbs were obtained from horses in an abattoir. Equine digital veins were carefully removed from distal portions of the forelimbs. Rings of dissected EDVs were mounted in 5-mL organ baths to record isometric tension in the presence of various beta3-AR agonists (SR 58611A, ZD 2079, and ZM 215001). Results: In intact EDVs, isoprenaline, SR 58611A,...
Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma). Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. Objective: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Methods: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. He...
Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells. Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaero...
The role of apoptotic regulators in metaplastic mucous cells. Exposure of airways to environmental toxins or allergens induces proliferation of epithelial cells. Depending on the type of exposure, existing and newly formed cells can differentiate into mucus-producing cells resulting in mucous cell metaplasia (MCM). During recovery, the epithelium reduces the number of epithelial cells to return to the original state. Understanding the mechanisms involved in this resolution could be useful in deleting mucous cells and, thereby, mucous secretions. We have found that metaplastic mucous cells induced by exposure to ozone, endotoxin, cigarette smoke or allerg...
Potentiation of the extracellular release of equine neutrophil elastase and alpha-1-proteinase inhibitor by a combination of two bacterial cell wall components: fMLP and LPS. Lipopolysaccharide (LPS) and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-like peptides are Gram-negative bacterial cell wall components which, when released into the peripheral circulation in endotoxaemia, have the potential to activate leucocytes. In vitro, equine neutrophils require priming with LPS in order to generate reactive oxygen intermediates (ROI) in response to fMLP. Objective: The aim of this study was to examine whether the release of other neutrophil products is similarly dependent on prior priming with LPS. In particular, neutrophil elastase (NE), a potent proteolytic enzyme,...
Effect of administration of a phospholipid emulsion on the initial response of horses administered endotoxin. To evaluate the effect of a phospholipid emulsion (PLE) on the initial response of horses to administration of endotoxin. Methods: 12 healthy adult horses. Methods: Horses were assigned to 2 treatment groups (6 horses/group). The control group was administered 1 L of saline (0.9% NaCl) solution, and the treated group was administered PLE (200 mg/kg, IV); treatments were administered during a period of 120 minutes. An infusion of endotoxin was initiated in both groups starting 1 hour after initiation of the saline or PLE solutions. Physical examination and hemodynamic variables were recorded, a...
High volume continuous venovenous haemofiltration (HV-CVVH) in an equine endotoxaemic shock model. Equine acute abdominal disease is often associated with shock. Important aspects in the onset of this complication include hypovolaemia, the translocation of endotoxins from the gut and the subsequent activation of the cytokine network. The clinical efficacy of high volume continuous venovenous haemofiltration (HV-CVVH) and the clearance of cytokines were therefore investigated in an equine endotoxaemic model. Ten male Shetland ponies received a slow infusion of LPS (2 microg/kg bwt) under general anaesthesia. The treatment group (n = 5) received HV-CVVH (2 ml/kg bwt/min) using a 75 kD polymet...
The effect of endotoxin administration on the secretory dynamics of oxytocin in follicular phase mares: relationship to stress axis hormones. The primary aim of this study was to define the secretory dynamics of oxytocin and vasopressin in pituitary venous effluent from ambulatory horses during acute endotoxaemia, a stimulus that may release both hormones. Our secondary aim was to investigate the role of oxytocin in regulating adrenocorticotropic hormone (ACTH) secretion by comparing oxytocin, vasopressin, corticotropin-releasing hormone (CRH) and ACTH secretory profiles during endotoxaemia and by monitoring the ACTH response to oxytocin administration. Pituitary venous blood was collected nonsurgically continuously and divided into...
Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 1: Preparation and composition of HDS. Currently, heaves is investigated by exposing susceptible horses to dusty hay. Consequently, the response will be dependent on the organic dust content and composition of the hay. It was hypothesised that the use of a hay dust suspension (HDS) would reduce the variability of the challenge and therefore standardise experimental protocols. Furthermore, analysis of HDS would also permit further investigation of the organic dust components responsible for the response. Three hay dust suspensions (HDS-1, 2 and 3) were prepared for use in the diagnosis and investigation of heaves. HDS were produced ...
Equine endotoxemia: pathomorphological aspects of endotoxin-induced damage in equine mesenteric arteries. To evaluate the effects of endotoxin on the morphology of the equine mesenteric vasculature, each of two thoroughbred horses were given two intravenous injections (24 h apart) of a sublethal dose of endotoxin (10 microg/kg). Each injection produced results similar to those of clinical cases of equine colic with obstructive nature of the loop of bowel: diarrhoea within 2 h after administration, followed by cessation of both faecal excretion and sounds of intestinal peristalsis. The most prominent morphological change was the development of moniliform appearance of small mesenteric arteries, in ...
Evaluation of lipopolysaccharide-induced activation of equine neutrophils. To evaluate lipopolysaccharide (LPS)-induced activation of equine neutrophils in blood. Methods: Blood samples from 5 healthy adult Thoroughbreds. Methods: Neutrophil integrin (CD11/CD18) expression, size variation, degranulation, and deformability were measured with and without incubation with LPS. Time and concentration studies were done. The mechanism of endotoxin-induced neutrophil activation was investigated by inactivating complement or preincubating neutrophils with inhibitors of tumor necrosis factor-alpha (TNF-alpha) synthesis, prostaglandin-leukotriene synthesis, or platelet-activati...
Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals. To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy. Methods: Blood samples from 10 healthy foals. Methods: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials. Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC. Whole blood or mononuclear cells grown in ...
