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.
Longworth KE, Smith BL, Staub NC, Steffey EP, Serikov VB.To determine whether a detergent can prevent most of the early effects of i.v. infusion with Escherichia coli endotoxin (< 100 ng/kg of body weight) in horses: marked pulmonary hypertension, acute leukopenia, and fever. Methods: 8 healthy adult horses (4 male, 4 female), 415 to 615 kg. Methods: Control and detergent experiments were performed in each horse while it was awake but sedated. In control experiments, 10 to 100 ng of E coli endotoxin/kg was given. In detergent experiments, 100 mg of detergent/kg was given 1 hour before injecting endotoxin, similar to the control experiments. Resul...
BonenClark GD, MacKay RJ, Ward RE, Sheerin B.To evaluate the humoral response of horses to vaccination, using a murine monoclonal anti-idiotypic antibody (A4) that shares an epitope with lipid A. Methods: Serum concentrations of antilipid A antibody and 1C9 (epitope on murine monoclonal antilipid A antibody) were measured serially during the period of vaccination with A4. Methods: 6 clinically normal adult ponies. Methods: Ponies were inoculated IM 3 times at monthly intervals with A4. Two weeks after each inoculation, serum was obtained and was assayed by ELISA for antilipid A and 1C9 concentrations. Additional vaccinations were given t...
Coté N, Trout DR, Hayes AM.The electrophoretic position and behavior of the native and activated forms of equine plasma alpha-2-macroglobulin (alpha 2M) were characterized and compared to human alpha 2M by nondenaturing polyacrylamide-gel electrophoresis (PAGE). Plasma alpha 2M was also compared between 6 normal horses and 6 horses with clinical signs of colic and endotoxemia due to volvulus or enteritis. Native and activated forms of alpha 2M were quantified by PAGE and densitometry. Binding of radio-labeled recombinant human tumour necrosis factor-alpha (125I-rhTNF-alpha) to native and activated forms of equine alpha ...
Jarvis GE, Evans RJ.Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The ef...
Cargile JL, MacKay RJ, Dankert JR, Skelley L.A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (Eq TNF) was used to investigate the role of TNF in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (IL-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-PGF1 alpha) were measured in 10 Miniature Horses given 0.25 microgram of lipopolysaccharide (LPS; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq TNF MAB and 5 were given isotype-matched MAB as control. All horses were given 1.86 mg of antibody/kg by IV...
Cargile JL, MacKay RJ, Dankert JR, Skelley L.Tumor necrosis factor-alpha (TNF) is an important mediator of endotoxin-induced pathologic changes. To help define the role of TNF in equids with endotoxemia, the effects of pretreatment with a murine monoclonal antibody (MAB) against equine TNF were evaluated in Miniature Horses given endotoxin. Five horses were given TNF MAB at a dosage of 1.86 mg/kg of body weight, IV, and 5 were given control MAB. Five minutes later, lipopolysaccharide (LPS; Escherichia coli O55:B5), 0.25 microgram/kg, was given to all horses by bolus IV infusion. Clinical signs of disease were monitored at intervals up to...
Hawkins DL, Cargile JL, MacKay RJ, Broome TA, Skelley LA.Six horses received intra-articular injections of a mixture of 1 micrograms of endotoxin/5 mg of equine tumor necrosis factor (eqTNF) monoclonal antibody in 1 antebrachiocarpal joint and an equal volume (2 ml) of 1 micrograms of endotoxin/5 mg of control antibody in the opposite joint. Synovial fluid sample collection (1 ml) was accomplished by use of an indwelling, intra-articular catheter at postinjection hours (PIH) 0, 1, 1.5, 2, 5, and 8, and by arthrocentesis at PIH 24. Joint fluid samples were analyzed for nucleated cell count, protein concentration, and TNF, interleukin 6 (IL-6), IL-1, ...
Collatos C, Barton MH, Prasse KW, Moore JN.Components of the coagulation and fibrinolytic cascades, prothrombin and activated partial thromboplastin times, endotoxin activity, and albumin concentration were measured in blood and peritoneal fluid from 20 healthy horses and from 153 horses with acute gastrointestinal tract diseases at admission. Overall, 77% (117/153) of affected horses survived to discharge from the hospital, and 85% (82/97) of horses discharged were reported to be normal 9 to 14 months later. Significant differences in hemostatic factors were more common in peritoneal fluid than in blood. Tissue plasminogen activator, ...
Mills PC, Ng JC, Seawright AA, Auer DE.Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of e...
Moore RM, Muir WW, Cawrse M, Bertone AL, Beard WL.Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Bloo...
Baxter GM.Low doses of endotoxin cause vasoconstriction and hypoperfusion of the digit, small intestine, and cecum in horses. To determine the potential cause of these vascular alterations, in vitro vascular responses of palmar digital arteries and veins were determined in 8 horses after intravenous (IV) infusion of 1 L 0.9% NaCl (control) and 0.1 microgram/kg Escherichia coli 055:B5 endotoxin in 1 L of 0.9% NaCl (endotoxin-treated). Vessels were surgically removed under general anesthesia, cut into 4-mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for measur...
Wagner AE, Dunlop CI, Wertz EM, Chapman PL, Baxter GM, Klopp LS.Seven horses, which were part of an investigation of the effect of endotoxin administration on vascular reactivity, were anesthetized on two separate occasions for surgical excision of 4-cm sections of palmar digital artery and vein. On the first occasion, the horses were given an infusion of 1 L 0.9% NaCl solution intravenously (i.v.) just before induction of anesthesia (control); on the second occasion, the horses received an infusion of 1 L 0.9% NaCl containing Escherichia coli endotoxin, 0.1 microgram/kg (endotoxin). On both occasions, anesthesia was induced with xylazine, guaifenesin, and...
Sandholm M, Vidovic A, Puotunen-Reinert A, Sankari S, Nyholm K, Rita H.The discriminating ability of 15 parameters alone or in combinations, including results from analysis of plasma endotoxin, the Nycomed plasma D-Dimer test and phospholipase A2, were analyzed to predict morbidity and mortality in equine gastrointestinal colic. Endotoxaemia was a characteristic feature of the colic horses. The problem of adequately predicting nonsurvivors among colic horses required several parameters to be included in the logistic model: if the "classical parameters", (heart rate, respiratory rate, PCV, anion gap) were included in the model, addition of plasma D-dimer, phosphol...
Holbrook TC, Moore JN.Endotoxemia and septicemia are encountered frequently in equine veterinary practice. The deleterious effects of endotoxin are related to the severity of the response of the host's inflammatory system. Consequently, it is imperative that appropriate steps be taken to identify animals at risk of developing endotoxemia or septicemia, and to initiate treatments that will reduce the inflammatory response. This article discusses the anti-inflammatory and immune support of horses and foals with endotoxemia and septicemia.
Barton MH, Moore JN.Whole blood from 10 healthy horses was aseptically collected into heparin or citrate anticoagulant and incubated in vitro for 6 hr in the absence (saline control) or presence of 1 ng endotoxin/ml blood. Pentoxifylline (0.1, 1, 10, or 100 micrograms/ml blood) was added 1 hr before, at the same time, or 1 hr after endotoxin. As compared to saline controls, pentoxifylline alone had no effect on mediator production, with the exception of significantly increasing 6-ketoprostaglandin F1 alpha concentration. Pentoxifylline inhibited endotoxin-induced increases in tumor necrosis factor (TNF) and inter...
Collatos C, Barton MH, Schleef R, Prasse KW, Moore JN.Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that repo...
Jarvis GE, Evans RJ.Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necess...
Palmer JL, Bertone AL.The use of extremely small dosages of intra-articular E. coli lipopolysaccharide (LPS) endotoxin can create a model of synovitis that mimics acute synovitis in horses. Dosages of 5000 ng, 25 ng, 0.5 ng, 0.25 ng, 0.17 ng and 0.125 ng per joint were injected into various joints of a total of 6 horses. The dose response of LPS on clinical signs and synovial fluid parameters was evaluated at baseline and 12, 24, 36 and 48 h after LPS injection. Peripheral venous blood analysis was performed at baseline and at 0, 4, and 12 h after LPS injection. Dosages greater than 0.5 ng/joint resulted in clinica...
Durando MM, MacKay RJ, Linda S, Skelley LA.Polymyxin B and an antiserum against an Re mutant Salmonella typhimurium were evaluated for protective effect in an equine model endotoxemia. Six 3- to 5-month-old foals were given endotoxin (0.25 micrograms/kg of body weight) IV after no pretreatment, or pretreatment with polymyxin B (6,000 U/kg, IV) or S typhimurium antiserum (1.5 ml/kg, IV). When given without pretreatment, endotoxin caused transient recumbency and increases in rectal temperature, and heart and respiratory rates. In addition, leukopenia and increases in circulating tumor necrosis factor (TNF) and interleukin 6 (IL-6) activi...
Weiss DJ, Geor RJ, Johnston G, Trent AM.The hypothesis that equine laminitis is caused by thrombosis of vessels in the laminar corium (dermis) was investigated. Hemostatic alterations were evaluated by determining platelet count, platelet survival, platelet adhesiveness to vascular subendothelium, activated clotting time, and whole blood recalcification time. Thrombosis of vessels in the hoof wall was evaluated by scintigraphic studies of the hoof wall after administration of indium-111 (111In)-labeled platelets, contrast arteriography, and histologic examination. Platelet count remained constant before and at the onset of lameness;...
Steverink PJ, Salden HJ, Sturk A, Klein WR, van der Velden MA, Németh F.In this study the laboratory and clinical performance of a chromogenic endotoxin assay for equine plasma was evaluated. The assay was sensitive (detection limit 3 ng LPS/L plasma), reproducible (within and between-assay CV at 50 ng LPS/L E. coli O111:B4 LPS standard addition was 5% and 7.5%, respectively), and not substantially affected by enhancement or inhibition phenomena (recovery of an in vitro spike was 75-125% in 80% of the samples). LPS added to whole blood was rapidly inactivated upon incubation at 37 degrees C but not at 0 degrees C. A recently developed blood collection tube for LPS...
Baxter G.Endotoxin given in vivo has been shown to inhibit endothelial dependent relaxation, and augment adrenergic (norepinephrine) contractions in isolated palmar digital arteries of horses. A study, using tumor necrosis factor (TNF) in vitro, was performed to determine the possible cause of these vascular alterations. Palmar digital arteries were surgically removed from 6 horses under general anesthesia, cut into 4-mm vascular rings (4 segments/horse), suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Four in vitro treatment groups were ev...
Jackman BR, Moore JN, Barton MH, Morris DD.The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo-oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end-products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiatin...
Seahorn TL, Gaunt SD, Berry C.Hematologic and rheologic variables were examined in a group of 13 horses with intestinal colic and a control group of 6 horses. All horses had been recently transported to the veterinary teaching hospital, and blood samples were obtained during initial examination. There were no significant differences in blood neutrophil count or plasma fibrinogen concentration between the groups, and PCV was significantly increased in horses with intestinal colic. Cell filterability was measured by passing uniform concentrations of blood, erythrocytes, and neutrophils through micropore filters. There were n...
Boening KJ, Leendertse IP.The medical records of pregnant mares over a 3-year period were reviewed. In all cases persistent pain or progressive abdominal distension were the main reason for referral. The overall survival rate for the 115 mares treated for colic was 73.9% (85 cases). The abortion rate was 20.5% in surgical patients (34 cases), 40% (5 cases) for mares with uterine torsions and 10.8% (46 cases) after medical treatment. The total abortion rate was 16.4%. Clinical evidence of endotoxaemia was, except for 1 mare, present in all the aborting mares after colic treatment. Anaesthesia did not appear to be a prob...
Allen GK, Green EM, Robinson JA, Garner HE, Loch WE, Walsh DM.We examined the effect of infusion of lipopolysaccharide (LPS) on serum tumor necrosis factor alpha (TNF alpha) concentration and clinical attitude in 2- 3-day-old colostrum-fed (CF) and colostrum-deprived (CD) foals. Eleven CF and 8 CD neonatal foals were given a bolus i.v. infusion of Escherichia coli O55:B5 lipopolysaccharide (0.5 microgram/kg of body weight) in sterile saline (0.9% NaCl) solution. Four CF and 2 CD foals were given saline solution alone. Serum IgG concentration and serum anti-LPS IgG(T) antibody titer were determined for each foal prior to infusion. A depression index was u...
Breuhaus BA, DeGraves FJ.Plasma endotoxin concentrations were measured at 1 to 2 and 5 to 6 days of age in clinically normal foals and in potentially septic neonatal foals admitted to North Carolina State University's Veterinary Teaching Hospital for a variety of conditions. In 1 to 2 and 5 to 6 day old normal foals, median plasma endotoxin concentrations were 2.17 (range, 1.61-2.54; n = 6) and 2.89 (range, 2.61-3.50; n = 7) endotoxin units/mL (EU/mL), respectively. Median plasma endotoxin concentration in potentially septic foals with negative blood cultures or gram positive isolates (n = 8) was 2.73 (range, 0.59-4.0...
Robinson JA, Allen GK, Green EM, Garner HE, Loch WE, Walsh DM.Serum interleukin-6 (IL-6) concentration was measured in 11 colostrum-fed (CF) and 8 colostrum-deprived (CD) 2- to 3-day-old foals after foals were infused with lipopolysaccharide (LPS; Escherichia coli O55:B5 endotoxin, 0.5 microgram/kg of body weight in sterile saline [0.9% NaCl] solution). Four CF and 2 CD foals were given saline solution alone. Serum IL-6 concentration was estimated by use of an in vitro proliferative bioassay, using the IL-6 dependent B.13.29 clone 9 cells. Interleukin-6 concentration increased in all LPS-infused foals, and geometric mean serum IL-6 concentration was sign...
Eades SC, Moore JN.Stimulation of alpha 2 adrenergic receptors inhibits colonic motility and may constrict some peripheral vascular beds. Endotoxemia elicits release of sympathetic neurotransmitters and increases sympathetic nerve activity, which may result in stimulation of alpha 2 adrenergic receptors. The objective of this study was to determine whether blockade of alpha 2 adrenergic receptors would restore cecal motility and blood flow during endotoxemia in horses. Strain-gauge force transducers and ultrasonic flow probes were used to measure cecal and colonic mechanical activity and lateral cecal arterial b...
Barton MH, Williamson L, Jacks S, Norton N.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...
Magnusson CB, Poulsen KP, Budde JA, Hartmann FA, Aulik NA, Raabis SM, Moreira ASD, Darien BJ, Peek SF.Periodic lack of availability and high cost of commercially produced isotonic fluids for intravenous (IV) use in horses have increasingly led to use of home-made or commercially compound fluids by veterinarians. Data regarding the quality control and safety of compounded fluids would be of benefit to equine veterinarians. Objective: To compare electrolyte concentrations, sterility, and endotoxin contamination of commercially available fluids to 2 forms of compounded isotonic crystalloid fluids intended for IV use in horses. Methods: Prospective study. Two methods of preparing compounded crysta...
MacKay RJ, Daniels CA, Bleyaert HF, Bailey JE, Gillis KD, Merritt AM, Katz TL, Johnson JC, Thompson KC.Ten horses were used in a crossover study to evaluate the effectiveness of eltenac against endotoxaemia. Eltenac (0.5 mg/kg bwt) or saline control was given i.v. then 15 min later, intravenous infusion of endotoxin was begun and continued for 120 min (total dose 100 ng/kg bwt). Horses were monitored for heart and respiratory rates, pulmonary and carotid arterial pressure and core body temperature. Blood was sampled at intervals for measurement of haematological variables and plasma concentrations of lactate, prostanoid metabolites, tumour necrosis factor (TNF) and stress hormones. In compariso...
Holbrook TC, Moore JN.Endotoxemia and septicemia are encountered frequently in equine veterinary practice. The deleterious effects of endotoxin are related to the severity of the response of the host's inflammatory system. Consequently, it is imperative that appropriate steps be taken to identify animals at risk of developing endotoxemia or septicemia, and to initiate treatments that will reduce the inflammatory response. This article discusses the anti-inflammatory and immune support of horses and foals with endotoxemia and septicemia.
Morris DD, Whitlock RH, Corbeil LB.An equine antiserum to core lipopolysaccharide was produced by inoculation of 6 horses with a boiled cell bacterin made from the J-5 mutant of Escherichia coli O111:B4. The antiserum immunoglobulin G titer to J-5 mutant E coli, as determined by enzyme-linked immunosorbent assay, was 1:15,006. Pooled serum prepared before inoculation (preimmune serum) had a J-5 immunoglobulin G titer of 1:350. The J-5 antiserum was tested for its protective efficacy in sublethal endotoxemia in 14 horses. Four horses served as nontreated controls and were given nothing before endotoxin challenge exposure (10 mic...
Templeton CB, Bottoms GD, Fessler JF, Ewert KM, Roesel OF, Johnson MA, Latshaw HS.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...
Menzies-Gow NJ, Bailey SR, Berhane Y, Brooks AC, Elliott J.To determine the effect of endotoxin (lipopolysaccharide [LPS]) on vasoactive mediator production by cultured equine digital vein endothelial cells (EDVECs). Methods: EDVECs obtained from forelimb digital veins of 7 healthy adult horses. Methods: EDVECs were incubated with or without LPS (1 microg/mL) for 0, 2, 4, 6, 22, and 24 hours. The EDVECs were incubated for 18 hours with LPS (10 pg/mL to 1 microg/mL) with or without ibuprofen, cycloheximide, or L-nitroarginine methyl ester. Medium concentrations of prostacyclin, cyclic guanosine monophosphate, endothelin-1, and thromboxane A(2) were det...
Seethanathan P, Bottoms GD, Schafer K.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....
Kelmer G, Doherty TJ, Elliott S, Saxton A, Fry MM, Andrews FM.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. Objective: 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 rando...
Patan-Zugaj B, Gauff FC, Plendl J, Licka TF.To investigate effects of endotoxin on leukocyte activation and infiltration of the laminar tissue in isolated perfused equine limbs. Methods: 10 right forelimbs and 3 left forelimbs collected from 10 healthy adult horses after slaughter at a licensed abattoir. procedures: Isolated right forelimbs were randomly assigned to 2 groups (5 forelimbs/group): perfusion of the distal portion for 10 hours with 80 ng of endotoxin/L and perfusion under the same conditions without endotoxin. After perfusion, samples for immunohistochemical detection of leukocytes (by use of antibodies against calprotectin...
Coté N, Trout DR, Hayes AM.The electrophoretic position and behavior of the native and activated forms of equine plasma alpha-2-macroglobulin (alpha 2M) were characterized and compared to human alpha 2M by nondenaturing polyacrylamide-gel electrophoresis (PAGE). Plasma alpha 2M was also compared between 6 normal horses and 6 horses with clinical signs of colic and endotoxemia due to volvulus or enteritis. Native and activated forms of alpha 2M were quantified by PAGE and densitometry. Binding of radio-labeled recombinant human tumour necrosis factor-alpha (125I-rhTNF-alpha) to native and activated forms of equine alpha ...
Alexander SL, Irvine CH.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...
Bailey SR, Cunningham FM, Elliott J.Uptake of 5-hydroxytryptamine (5-HT) into platelets is an important mechanism by which low plasma concentrations are maintained, and platelet activation may therefore result in significant release of this vasoconstrictor. The present study examined the kinetics of active uptake of radiolabelled [3H]5-HT by washed equine platelets in vitro, and investigated the effects on this process of 4 other naturally occurring monoamines which may be released from the caecum in conditions of carbohydrate overload. The release of [3H]5-HT by platelets was also studied, since platelet accumulation and activa...
Ross MW, Martin BB, Donawick WJ.The case records of 23 horses with cecal perforation (CP) were reviewed. The horses averaged 4.5 years of age (6 weeks to 13 years) and included 9 intact males, 12 mares, and 2 geldings. Twelve of the horses were Standardbreds, 9 were Thoroughbreds, and 1 each, a Belgian and Morgan. The horses were allotted to 2 groups: group I-13 hospitalized horses in which CP occurred unexpectedly, and group II-10 horses with CP at the time of admission. The horses characteristically had been sick or affected with disease unrelated to the cecum. Sixteen horses had been given nonsteroidal anti-inflammatory d...
Duncan SG, Meyers KM, Reed SM, Grant B.This experiment was designed to establish a model for the study of gastrointestinal disturbances as a result of prolonged endotoxin uptake in the horse. The hepatic portal vein of 7 horses was catheterized (through flank incisions) to give chronic hepatic portal infusions of lipopolysaccharide (LPS, endotoxin). Lipopolysaccharide was infused at a rate of 1 microgram/kg of body weight/hr for 24 hours. Two of the horses were infused with saline solution for 12 hours before LPS infusions were given. Lipopolysaccharide was shown to affect behavior and hematologic and coagulation values. The 1st ho...
Oikawa M, Ohnami Y, Koike M, Park CH, Oyamada T.To evaluate the effects of endotoxin on the morphology of the equine central, autonomic and enteric nervous system and intestinal muscularis, six Thoroughbred horses with experimentally induced endotoxaemia were examined. The lesions in the central nervous system consisted of perivascular oedema around arterioles, suggesting brain oedema, and ring haemorrhages around veins, similar to those in human patients with septic shock. In the cranial mesenteric ganglia, neuronal cell bodies became pink or red, with shrinkage of cytoplasm indicative of ischaemic changes; intramural and perivascular infi...
Kilcoyne I, Nieto JE, Watson JL, Galuppo LD, Borjesson DL.Endotoxemia is a leading cause of morbidity and mortality in the equine industry, with colic being the most common cause of endotoxemia in horses. The objective of this study was to evaluate the safety and potential efficacy of a single dose of allogeneic equine bone marrow derived mesenchymal stem cells (BM-MSCs) in horses after the IV administration of lipopolysaccharide (LPS). Six horses were administered an IV infusion of 30 ng/kg LPS (O55:B5 Escherichia coli) in 500 ml saline over 30 min. Immediately after infusion test horses (n = 3) were administered 100 × 10 allogeneic BM-MSCs diluted...
Breuhaus BA, DeGraves FJ.Plasma endotoxin concentrations were measured at 1 to 2 and 5 to 6 days of age in clinically normal foals and in potentially septic neonatal foals admitted to North Carolina State University's Veterinary Teaching Hospital for a variety of conditions. In 1 to 2 and 5 to 6 day old normal foals, median plasma endotoxin concentrations were 2.17 (range, 1.61-2.54; n = 6) and 2.89 (range, 2.61-3.50; n = 7) endotoxin units/mL (EU/mL), respectively. Median plasma endotoxin concentration in potentially septic foals with negative blood cultures or gram positive isolates (n = 8) was 2.73 (range, 0.59-4.0...
Frauenfelder HC, Fessler JF, Moore AB, Bottoms GD, Boon GD.The effects of dexamethasone (1 mg/kg of body weight) on hematologic, blood gas, and blood coagulation values in anesthetized ponies during endotoxin-induced shock were evaluated. Fifteen ponies were assigned to 3 groups of 5 ponies each: group 1, anesthetized nontreated and dexamethasone-treated controls; group 2, endotoxin, nontreated; group 3, endotoxin, dexamethasone treated. The hematologic changes in this endotoxin shock model included leukopenia and hemoconcentration. Significant hematologic effects were not seen in ponies after administration of dexamethasone. However, dexamethasone tr...
Allen GK, Campbell-Beggs C, Robinson JA, Johnson PJ, Green EM.Six, clinically healthy horses, of mixed age and sex, were infused via a jugular venous catheter with 100 ml of pyrogenfree sterile saline (PFSS; 0.9% NaCl). Animals were infused with Escherichia coli O55:B5 endotoxin (total dose = 50 ng/kg bwt), 24 (LPS-1) and 48 h (LPS-2) after PFSS infusion. Blood was collected before, and every 15 min after, each infusion for the first 8 h and then every 2 h for the following 14 h. Clinical responses (rectal temperature, heart rate, respiration rate and blood pressure) were determined before and every 4 h after each infusion for 20 h. Geometric mean anti-e...
Ouellette AL, Evans RJ, Heath MF.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...
Turek JJ, Templeton CB, Bottoms GD, Fessler JF.Endotoxic shock was induced in 5 ponies by intraperitoneal injections of 20, 40, 60, 80, and 80 micrograms of Escherichia coli endotoxin (LPS)/kg of body weight at 0, 6, 12, 18, and 24 hours, respectively. At 24 hours, the ponies also were given 20 micrograms of LPS/kg via catheter in the left ventricle of the heart. A 2nd group of 4 ponies was given 1.1 mg of flunixin meglumine (FM)/kg, IV, at 6, 12, 18, and 24 hours just before the corresponding LPS injection. Two hours after the 24-hour LPS injection, the ponies in both groups were anesthetized, the lungs were perfused with fixative, and po...
Bailey SR, Elliott J.Endotoxin has been implicated in the pathophysiology of acute laminitis. The aim of this study was to examine the direct effects of endotoxin on isolated equine digital blood vessels. Equine digital veins (EDV), incubated in Krebs-Henseleit solution containing lipopolysaccharide (LPS) (1 microg/ml) became hyporesponsive to 5-HT after 16 h. Cycloheximide and ibuprofen blocked this effect of LPS and increased the maximum response obtained to 5-HT when compared to control vessels. L-nitroarginine methyl ester (L-NAME) reversed the hyporesponsiveness caused by LPS. Vessels maintained in culture me...
Daels PF, Stabenfeldt GH, Hughes JP, Odensvik K, Kindahl H.The role of decreased luteal activity in embryonic loss after induced endotoxemia was studied in mares 21 to 35 days pregnant. Fourteen pregnant mares were treated daily with 44 mg of altrenogest to compensate for the loss of endogenous progesterone secretion caused by prostaglandin F2 alpha (PGF2 alpha) synthesis and release following intravenous administration of Salmonella typhimurium endotoxin. Altrenogest was administered daily from the day of endotoxin injection until day 40 of gestation (group 1; n = 7), until day 70 (group 2; n = 5), or until day 50 (group 3; n = 2). In all mares, secr...
Barton MH, Ferguson D, Davis PJ, Moore JN.Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F1 alpha were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at ...
Weld JM, Kamerling SG, Combie JD, Nugent TE, Woods WE, Oeltgen P, Tobin T.The effects of naloxone on the cardiovascular, hematologic and metabolic derangements associated with endotoxic and hemorrhagic shock were studied in unanesthetized horses. In the first of 3 experiments blood glucose and lactate levels, hematocrit, white, red and differential white cell counts, rectal temperature and clinical signs were obtained before and after endotoxin (10 micrograms/Kg) administration in 5 horses. In the second experiment, two groups of 3 horses received either intravenous naloxone (0.04 mg/Kg) or saline, 7 minutes prior to endotoxin. In a third experiment two groups of 4 ...
Semrad SD, Moore JN.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 ...
Moore JN, Garner HE, Shapland JE, Hatfield DG.Effects of a sublethal IV dose (10 micrograms/kg of body weight) of Escherichia coli endotoxin were studied in 7 conscious ponies. Arterial blood gases and plasma lactic acid were determined periodically throughout the 180 minutes of the study. Arterial hypoxemia occurred within 5 minutes despite intense hyperventilation. Colic and diarrhea occurred in all ponies within 30 minutes after endotoxin administration. Metabolic acidosis developed within 30 minutes and persisted throughout the study, indicating widespread reduced tissue perfusion.
Mills PC, Ng JC, Seawright AA, Auer DE.Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of e...
