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.
Bailey SR, Adair HS, Reinemeyer CR, Morgan SJ, Brooks AC, Longhofer SL, Elliott J.The link between the fermentation of carbohydrate in the equine large intestine and the development of acute laminitis is poorly understood. Absorption of endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one experimental model of laminitis, but does not cause laminitis when administered alone. Thus, the potential role of endotoxin is unclear. Platelet activation has previously been demonstrated in the developmental stage of laminitis. Equine platelets are more sensitive than leukocytes to activation by endotoxin, and can be activated directly by LPS in the low pg/ml ran...
Brooks AC, Menzies-Gow NJ, Wheeler-Jones C, Bailey SR, Cunningham FM, Elliott J.The endothelium plays a major role in the pathogenesis of endotoxemia. Binding of endotoxin (lipopolysaccharide; LPS) to endothelium initiates a range of signalling events, including activation of p38 mitogen activated protein kinases (MAPKs) that are involved in the initiation of inflammatory responses. In the present study we have examined whether clinically relevant concentrations of LPS can activate p38 MAPK in equine endothelial cells and have investigated the role of the kinase in neutrophil adhesion and mediator release. Cultured equine digital vein endothelial cells (EDVEC) were expose...
Berndt A, Derksen FJ, Edward Robinson N.Inflammatory airway disease is common in stabled horses, with a prevalence of 17.3% in Michigan pleasure horses. Stable dust is rich in endotoxin, which may induce neutrophilic airway inflammation. Climatological conditions (ambient temperature and relative humidity) may influence endotoxin concentrations in pastures. The aim of this project was to determine if endotoxin levels in the breathing zone of horses in stables were higher than of horses on pasture, and if the endotoxin on pasture was associated with climatological conditions. Endotoxin exposure of six horses that were stabled or on p...
Figueiredo MD, Moore JN, Vandenplas ML, Sun WC, Murray TF.To evaluate proinflammatory effects of the second-generation synthetic lipid A analogue E5564 on equine whole blood and isolated monocytes and to determine the ability of E5564 to prevent LPS (lipopolysaccharide)-induced procoagulant activity (PCA); tumor necrosis factor (TNF)-alpha production; and mRNA expression of TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 by equine monocytes. Methods: Venous blood samples obtained from 19 healthy horses. Methods: Whole blood and monocytes were incubated with Escherichia coli O111:B4 LPS, E5564, or E5564 plus E coli O111:B4 LPS. Whole blood and cell...
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...
Cook VL, Jones Shults J, McDowell M, Campbell NB, Davis JL, Blikslager AT.Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. Objective: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. Methods: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flun...
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...
Menzies-Gow NJ, Sepulveda MF, Bailey SR, Cunningham FM, Elliott J.To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF) in endotoxin-induced digital hypoperfusion in horses. Methods: 6 healthy adult Thoroughbreds. Methods: Horses were treated with IV administration of saline (0.9% NaCl) solution (control treatment) or the 5-HT 1B/D selective antagonist, GR55562 (0.3 mg/kg), prior to tryptamine infusion (1.6 microg/kg/min for 30 minutes) to establish an effective GR55562 dose. In a crossover study, horses were treated with IV administration of saline solution (control treatment), aspirin (4 mg/kg, 2 h...
Pantaleon LG, Furr MO, McKenzie HC, Donaldson L.Small-volume resuscitation (SVR) has been advocated in place of large-volume isotonic resuscitation for the treatment of endotoxemia in horses. The effects of this type of therapy during experimental endotoxemia on electrolytes and coagulation have not been evaluated in the horse. As part of a larger project, the objective of this study was to determine the effects of SVR (hypertonic saline solution [HSS] plus hetastarch [HES]) on coagulation and serum electrolytes concentration, and to compare SVR with large- and small-volume isotonic resuscitation during experimental endotoxemia in anestheti...
Tóth F, Frank N, Elliott SB, Geor RJ, Boston RC.To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses. Methods: 16 healthy adult mares. Methods: Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via min...
Valentine BA, Löhr CV.Three horses with colic, clinical evidence of endotoxaemia and high serum activities of creatine kinase and aspartate aminotransferase were examined postmortem. The horses were diagnosed with severe ulcerative colitis, pyloric ulceration and stenosis with colonic sand impaction, and colonic obstruction due to faecaliths. There was no gross or histological evidence of muscle trauma. Their semimembranosus muscles had scattered acute to subacute segmental necrosis of the myofibres, suggestive of endotoxin-induced muscle injury.
Donovan DC, Jackson CA, Colahan PT, Norton N, Hurley DJ.Using an established standardized exercise test on a high-speed treadmill, thirteen Thoroughbred racehorses were exercised to fatigue (failure); blood samples were obtained before exercise, at failure, and at 2, 6, 24, 48, and 72 h after exercise. The exercise test induced a systemic inflammatory response characterized by a mild transient endotoxemia, leukocytosis, increased leukocyte expression of mRNA for tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, and IL-6, and increased circulating concentrations of TNF-alpha and prostaglandin F2 alpha (PGF 2 alpha), with the most pronounced change...
Moore JN, Norton N, Barton MH, Hurley DJ, Reber AJ, Donovan DC, Vandenplas ML, Parker TS, Levine DM.Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis. Objective: Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro. Methods: Twelve healthy horses received an i.v. infusion either of saline or a phospholipid em...
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...
Parsons CS, Orsini JA, Krafty R, Capewell L, Boston R.To identify risk factors for development of acute laminitis in horses during hospitalization for illness or injury. Methods: Retrospective case-control study. Methods: 73 horses that developed laminitis (case horses) and 146 horses that did not develop laminitis (control horses) during hospitalization. Methods: Case and control horses were matched in a 2:1 ratio by the date on which each horse was evaluated. Potential risk factors investigated included age, breed, and sex; highest and lowest values recorded during hospitalization for fibrinogen concentration, WBC count, PCV, and total solids c...
Pantaleon LG, Furr MO, McKenzie HC, Donaldson L.Small volume resuscitation has been advocated as a beneficial therapy for endotoxemia in horses but this therapy has not been investigated in a prospective manner. The objective of this study was to determine the cardiopulmonary effects of small-volume resuscitation using hypertonic saline solution (HSS) plus Hetastarch (HES) during experimental endotoxemia in anesthetized horses. Objective: Treatment of horses with induced endotoxemia using HES-HSS does not alter the response of various cardiopulmonary indices when compared to treatment with either small- or large-volume isotonic crystalloid ...
Danek J.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 th...
Peek SF, Semrad S, McGuirk SM, Riseberg A, Slack JA, Marques F, Coombs D, Lien L, Keuler N, Darien BJ.This prospective study compared survival rates of critically ill and septic foals receiving 1 of 2 different types of commercial equine plasma and analyzed admission variables as possible predictors of survival. Standardized clinical, hematologic, biochemical, and hemostatic admission data were collected and foals received either conventional commercially available hyperimmune equine plasma or equine plasma specifically rich in antiendotoxin antibodies in a double-blinded, coded fashion. Sepsis was defined as true bacteremia or sepsis score >11. Overall survival rate to discharge was 72% (4...
Singh Suri S, Janardhan KS, Parbhakar O, Caldwell S, Appleyard G, Singh B.Toll-like receptor (TLR) is a key component in launching innate immune response to microbial challenge. TLR4 and TLR2 are recognized as specific receptors for components of Gram-negative and Gram-positive bacteria, respectively. Horses are extremely sensitive to endotoxin-induced cardiopulmonary distress and mortality which causes significant economic losses. To date, there are no data on the expression of TLR4 and TLR2 in horse lungs. Therefore, we examined the expression of TLR4 and TLR2 in lungs from normal or Escherichia coli lipopolysaccharide (E. coli LPS; 50 ng/kg; iv) treated horses. W...
Morresey PR, Mackay RJ.To measure serum polymyxin B concentration after single and repeated IV infusions in horses. Methods: 5 healthy horses. Methods: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion a...
Oikawa M, Masawa N, Yoshikawa H.To test the hypothesis that mesenteric arterionecrosis (MA) occurs in horses with naturally occurring endotoxaemia (ET) and in those with experimentally induced ET, the mesentery and gastrointestinal tract of 21 Thoroughbred racehorses (15 with spontaneous colic suspected to be due to ET, and six with experimentally induced ET) were examined. MA, which occurred in 13 of the 15 horses with spontaneous colic and in all six of the cases of experimental ET, was morphologically similar in the two groups of animals. This suggested that the pathogenesis of the MA was fundamentally similar in the two ...
Airaksinen S, Heiskanen ML, Heinonen-Tanski H, Laitinen J, Laitinen S, Linnainmaa M, Rautiala S.Respiratory exposure to organic dust induces chronic pulmonary diseases both in farmers and horses. The aim of this study was to examine the variation of dustiness and hygiene quality of peat moss bedding. Materials studied were weakly decomposed sphagnum peat (A), weakly decomposed sphagnum peat warmed up in storage (> 30 degrees C) (B) and two more decomposed few-flowered sedge peats (C and D). The geometric mean of mesophilic fungi, thermotolerant fungi and thermophilic actinomycetes were determined from the material. Samples of inhalable dust and endotoxins were collected with IOM samplers...
Smith CL, Dowling BA, Dart AJ.Laparoscopy is a minimally invasive procedure that has applications as a diagnostic, therapeutic and prognostic technique. Specialized equipment is necessary to perform equine laparoscopy, and there is a large range of instruments, both disposable and non-disposable available. Laparoscopic procedures described include ovariectomy, cryptorchidectomy, adhesiolysis and herniorrhaphy. Laparoscopy can be performed in a standing or dorsally recumbent position, depending on surgeon preference, patient status and the procedure to be performed. Stapling equipment is frequently used in gastrointestinal ...
Sykes BW, Furr MO.The pathophysiology of endotoxaemia, a leading cause of death in the horse, is beginning to be understood in greater detail. Endotoxin may be absorbed into the systemic circulation in a number of different ways: most commonly the body's normal defense mechanisms are disrupted or bypassed, or the normal clearance mechanisms overwhelmed. Following this wide-spread effects are observed, although the most significant are seen in the cardiovascular system. Fever, arterial hypoxaemia and signs of abdominal pain are also common. With increased understanding of the disease new therapeutic agents have ...
Parbhakar OP, Duke T, Townsend HG, Singh B.Horses are unique in their extreme sensitivity to endotoxin-induced cardio-pulmonary shock and mortality. The mechanisms behind increased sensitivity of the horse to endotoxin remain unknown. Pulmonary intravascular macrophages (PIMs) are pro-inflammatory cells occurring in horses. Because the functions of equine PIMs in endotoxemia remain unknown, we studied the role played by equine PIMs in endotoxin-induced pulmonary pathophysiology. We achieved this by using a recently developed protocol to deplete PIMs in order to compare lipopolysaccharide (LPS)-induced pulmonary responses in horses with...
Sykes BW, Furr M, Giguère S.Twelve healthy horses were assigned to treatment or control groups. Treated horses received PGG-Glucan[ED-1] (1 mg/kg, IV) 24 hours prior to peripheral blood mononuclear cell (PBMC) isolation. PBMCs were isolated and incubated in the presence of lipopolysachharide (LPS). At 0, 6, 12, 24 and 48 hours messenger RNA (mRNA) was extracted. Reverse transcription polymerase chain reaction (PCR) was performed and cytokine mRNA expression for tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), interleukin 10 (IL-10) and interferon gamma (IFN-gamma) determined using real time PCR. A si...
Menzies-Gow NJ, Bailey SR, Stevens K, Katz L, Elliott J, Marr CM.To measure plasma endothelin-1 (ET-1) concentrations and digital blood flow in clinically endotoxemic horses. Methods: 36 adult horses that underwent emergency celiotomy for primary gastrointestinal tract disease. Methods: On days 2 and 5 following surgery, Doppler ultrasonographic digital arterial blood flow measurements were obtained. Hematologic and biochemical analyses were performed, and plasma concentrations of ET-1 and endotoxin (lipopolysaccharide) were determined. A scoring system based on 9 clinical variables was used to assign horses to group B (quartile with greatest cumulative sco...
Toribio RE, Kohn CW, Hardy J, Rosol TJ.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...
Zerpa H, Vega F, Vasquez J, Ascanio E, Campos G, Sogbe E, Romero E, Ascanio M, García H.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...
Moore JN, Garner HE, Berg JN, Sprouse RF.Cecal fluid from two adult horses was assayed by the limulus amebocyte lysate system for endotoxin before and after carbohydrate overload of the gastrointestinal tract. There were increases in cecal fluid endotoxin concentrations at the 3-, 6-, and 12-hour samplings when compared with base-line values. Concomitant cecal fluid lactate concentrations and pH values increased and decreased, respectively. Both horses subsequently developed clinical signs of acute laminitis.
Burrows GE.Endotoxins are non-protein fragments of the cell wall of Gram-negative bacteria. They must be absorbed into the circulation to produce disease and systemic effects are similar, regardless of bacterial source. Absorption of endotoxins occurs in obstructive bowel disease and may play a significant part in determining the severity of the disease. Many of the responses to experimentally administered endotoxin are identical to those of bowel diseases or the horse and include circulatory, haematological and metabolic alterations. Therapeutic approaches are indirect and include many drugs currently e...
Smith CL, Dowling BA, Dart AJ.Laparoscopy is a minimally invasive procedure that has applications as a diagnostic, therapeutic and prognostic technique. Specialized equipment is necessary to perform equine laparoscopy, and there is a large range of instruments, both disposable and non-disposable available. Laparoscopic procedures described include ovariectomy, cryptorchidectomy, adhesiolysis and herniorrhaphy. Laparoscopy can be performed in a standing or dorsally recumbent position, depending on surgeon preference, patient status and the procedure to be performed. Stapling equipment is frequently used in gastrointestinal ...
Valk N, Doherty TJ, Blackford JT, Abraha TW, Frazier DL.The effect of phenylbutazone on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal fasted horses (n = 6), horses given endotoxin intravenously (n = 6), horses given intravenous phenylbutazone (n = 6), and horses given intravenous phenylbutazone plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration versus time curve (AUC) were compared among treatment groups. Phenylbutazone...
Baker B, Gaffin SL, Wells M, Wessels BC, Brock-Utne JG.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...
Weiss DJ, Evanson OA.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...
Pantaleon LG, Furr MO, McKenzie HC, Donaldson L.Small volume resuscitation has been advocated as a beneficial therapy for endotoxemia in horses but this therapy has not been investigated in a prospective manner. The objective of this study was to determine the cardiopulmonary effects of small-volume resuscitation using hypertonic saline solution (HSS) plus Hetastarch (HES) during experimental endotoxemia in anesthetized horses. Objective: Treatment of horses with induced endotoxemia using HES-HSS does not alter the response of various cardiopulmonary indices when compared to treatment with either small- or large-volume isotonic crystalloid ...
Fossum C, Hjertner B, Olofsson KM, Lindberg R, Ahooghalandari P, Camargo MM, Bröjer J, Edner A, Nostell K.The expression of tlr4, md2 and cd14 was studied in equine blood leukocytes and in intestinal samples using real time PCR. The stability of three commonly used reference genes, glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxantine ribosyltransferase (HPRT) and succinate dehydrogenase complex subunit A (SDHA), was evaluated using qbase(PLUS). The equine peripheral blood mononuclear cells (eqPBMC) examined were either stimulated in vitro with Phorbol 12-myristate 13-acetate (PMA) and ionomycin or with the CpG oligodeoxynuclotide 2216 (CpG-ODN 2216) or obtained from horses before, during and after...
Frellstedt L, McKenzie HC, Barrett JG, Furr MO.Endotoxemia is responsible for severe illness in horses. Individuals can become clinically unresponsive to the endotoxin molecule after an initial exposure; a phenomenon referred to as 'endotoxin tolerance' (ET). ET has been observed clinically in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMC) in vitro, and to describe selected cytokine responses which are associated with ET. ET was induced by culturing cells with three c...
Werners AH.Endotoxins, constituents of the cell wall of gram-positive and gram-negative bacteria, regularly result in severe illness and death in horses. In endotoxaemia, these constituents are present in the systemic circulation; in septicaemia, whole microbes invade normally sterile parts of the body. Interaction of these endotoxins with pathogen recognition receptors leads to an inflammatory response that cannot always be sufficiently contained and hence needs direct treatment. Over the last decennia, our understanding of the pathophysiology of endotoxaemia and septicaemia has significantly increased....
Smith TA, Davis E, Carpenter S.Lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. To determine the effects of macrophage activation on replication of equine infectious anaemia virus (EIAV), primary horse macrophage cultures (HMCs) were established from 20 different horses, infected with an avirulent strain of EIAV, and stimulated with 5 microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed for the presence of tumour necrosis factor (TNF-alpha) and for production of infectious virus. Results indicated that EIAV replicati...
Gomez DE, Leclere M, Arroyo LG, Li L, John E, Afonso T, Payette F, Darby S.This study describes the clinicopathological findings, diagnostic approach, treatment, and factors associated with non-survival of diarrheic horses admitted to 4 Canadian university teaching hospitals between 2015 and 2019. A total of 300 horses, ≥1-year-old, with acute diarrhea were included and represented 1.6% (300/18 481; range: 0.7 to 3%) of admissions during that period, 70% of the horses survived to discharge. Testing for enteropathogens was limited to a single fecal culture for Salmonella spp. in most cases. An enteropathogen was identified in 14% (42/300) of the horses, but in the h...
Morris DD, Moore JN, Fischer K, Tarleton RL.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...
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...
Daels PF, Stabenfeldt GH, Hughes JP, Odensvik K, Kindahl H.The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium...
Wong DM, Sponseller BA, Alcott CJ, Agbedanu PN, Wang C, Hsu WH.To evaluate the effect of IV administration of polymyxin B on clinical and serum biochemical variables in foals with experimental endotoxemia. Methods: Prospective experimental study. Methods: 14 healthy neonatal foals. Methods: Foals were randomly assigned to a treatment or control group and were administered a single dose of lipopolysaccharide (0.5 μg/kg [0.23 μg/lb]) IV over 30 minutes. The treatment group received polymyxin B (6,000 U/kg [2,727 U/lb], IV) immediately after completion of lipopolysaccharide infusion; the control group was administered an equal volume of saline (0.9% NaCl) ...
Anderson MJ, Ibrahim AS, Cooper BR, Woolcock AD, Moore GE, Taylor SD.Sepsis is associated with ascorbic acid (AA) depletion and critical illness-related corticosteroid insufficiency (CIRCI) in humans. Objective: Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. Methods: Thirty-two healthy horses. Methods: Randomized placebo-controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were admin...
Brooks AC, Menzies-Gow NJ, Wheeler-Jones C, Bailey SR, Cunningham FM, Elliott J.The endothelium plays a major role in the pathogenesis of endotoxemia. Binding of endotoxin (lipopolysaccharide; LPS) to endothelium initiates a range of signalling events, including activation of p38 mitogen activated protein kinases (MAPKs) that are involved in the initiation of inflammatory responses. In the present study we have examined whether clinically relevant concentrations of LPS can activate p38 MAPK in equine endothelial cells and have investigated the role of the kinase in neutrophil adhesion and mediator release. Cultured equine digital vein endothelial cells (EDVEC) were expose...
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...
Khumsap S, Lanovaz JL, Rosenstein DS, Byron C, Clayton HM.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...
Jánosi S, Huszenicza G, Kulcsár M, Kóródi P.After giving an overview of the general pathology of endotoxin-mediated diseases, the authors summarise the endotoxin-induced endocrine changes and their clinical consequences, with particular regard to reproduction. The consequences of temporary activation of the cyclooxygenase-2 and lipoxygenase enzyme systems resulting in elevated release of various prostanoids are discussed in cyclic and pregnant ruminants, sows and mares. The clinical failures attributable to increased glucocorticoid secretion as well as the endotoxin-induced changes in thyroid function and in peripheral level of some oth...
Daels PF, Starr M, Kindahl H, Fredriksson G, Hughes JP, Stabenfeldt GH.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...
Dunkle NJ, Bottoms GD, Fessler JF, Knox K, Roesel OF.A study was conducted to determine whether body fluids undergo a net shift from one compartment to another during endotoxin-induced shock in the pony, and whether flunixin meglumine alters these endotoxin-induced changes in the volumes of body fluid compartments. Total blood, RBC, and plasma volumes were determined, using 51Cr-labeled RBC and PCV that were corrected for trapped plasma. Total body water was measured by distribution of 3HOH. Arterial blood pressure was measured directly, using a blood pressure transducer. Treatment (flunixin meglumine, 1.1 mg/kg of body weight) was given to 6 of...
Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Fortes B, Thompson R, Linden J.Adenosine is an endogenous nucleoside that has potent receptor-mediated immunomodulatory effects on macrophage/monocyte function. In this study, we determined the effects of an adenosine A(2A) receptor agonist, ATL313, on the expression of mRNAs for four pro-inflammatory mediators, IL-1beta, IL-8, COX-2, and TNF-alpha, and the mRNA and protein for the anti-inflammatory cytokine, IL-10 in equine monocytes incubated with lipopolysaccharide (LPS). The results indicate that ATL313 significantly reduces LPS-induced expression of COX-2 and TNF-alpha, enhances the expression of IL-10 and IL-8, but do...
Valk N, Doherty TJ, Blackford JT, Abraha TW, Frazier DL.The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted ...
MacKay RJ, Clark CK, Logdberg L, Lake P.To determine the efficacy of polymyxin B-dextran 70 (PBD) for treatment of endotoxemic horses. Methods: 15 horses during study 1 and 6 horses during study 2. Methods: 3 groups were used in study 1. Horses in groups 1 and 2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes. Horses in group 3 were given saline (0.9% NaCl) solution. Beginning 15 minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and 3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were obtained for hemograms and determination of cytokine, lac...
Morris DD, Moore JN, Crowe N, Moldawer LL.A study was conducted to determine whether serum interleukin-6 (IL-6) activity increased in horses during experimentally induced endotoxemia and whether serum IL-6 activity correlated to changes in clinical or laboratory data. Six clinically normal horses were given endotoxin IV (30 ng/kg of body weight) in 0.9% NaCl solution over 1 hour. Five of these and 1 additional horse served as controls and were given only 0.9% NaCl solution. Venous blood, for determination of serum IL-6 activity and WBC count, was collected before and at various times through 8 hours after the start of endotoxin or NaC...
Airaksinen S, Heiskanen ML, Heinonen-Tanski H, Laitinen J, Laitinen S, Linnainmaa M, Rautiala S.Respiratory exposure to organic dust induces chronic pulmonary diseases both in farmers and horses. The aim of this study was to examine the variation of dustiness and hygiene quality of peat moss bedding. Materials studied were weakly decomposed sphagnum peat (A), weakly decomposed sphagnum peat warmed up in storage (> 30 degrees C) (B) and two more decomposed few-flowered sedge peats (C and D). The geometric mean of mesophilic fungi, thermotolerant fungi and thermophilic actinomycetes were determined from the material. Samples of inhalable dust and endotoxins were collected with IOM samplers...
