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.
Denkhaus M, Van Amstel S.Non-commercial, endotoxin positive, intravenous fluids as well as a commercially available intravenous fluid were given to clinically normal horses. Endotoxin-positive fluids caused clinical signs attributable to endotoxaemia. Leukopenia, preceded by a fluctuating white cell count, was observed in horses showing clinical signs. The commercial intravenous fluid had no effect on the white cell count or on the clinical state. Precautions to be taken and recommendations are made with regard to the monitoring of horses in which one might be forced to use non-commercial intravenous fluids.
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...
Moore JN, Hardee MM, Hardee GE.Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight...
Olson NC.Effects of endotoxemia on lung water, hemodynamics, and gas exchange were determined in ponies breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused IV at 20 micrograms/kg of body weight for 1 hour followed by 10 micrograms/kg/hr the subsequent 4 hours. By 0.25 hour, endotoxin increased mean pulmonary artery pressure and pulmonary vascular resistance; this was followed by a return to base-line values by 0.5 and 1 hour, respectively. A 2nd increase in pulmonary vascular resistance occurred by 5 hours of endotoxemia. During the last 2 hours of endotoxin infusion, c...
Olson NC, Meyer RE, Anderson DL.The effects of endotoxemia on cardiopulmonary parameters, before and after cyclooxygenase blockade, were determined in anesthetized ponies spontaneously breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT), and these were followed by a return to base-line values by 30 min. A second increase in PVR occurred by 5 h ...
Blanchard TL, Elmore RG, Kinden DA, Berg JN, Mollett TA, Garcia MC.Fifteen pony mares were assigned to 1 of 3 treatment groups after foaling: Group 1, 35 ml of sterile saline solution was infused into the uterine lumen within 24 hours after parturition (6 mares); group 2, 300 mg of Escherichia coli endotoxin was infused into the uterine lumen within 24 hours after parturition (6 mares); and group 3, 300 mg of E coli endotoxin was infused into the uterine lumen between 72 and 96 hours after parturition (3 mares). Rectal temperatures were taken at -1, -0.5, 0, 0.5, 1, 1.5, 2, 3, 4, and 5 hours after treatment. Venous blood samples were also taken at these times...
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...
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...
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...
Spurlock GH, Landry SL, Sams R, McGuirk S, Muir WW.Plasma volume, extracellular fluid volume (ECFV), and total body water (TBW) were measured before and after endotoxin (Escherichia coli) administration in 6 conscious adult horses. Evan's blue dye, sodium thiocyanate, and antipyrine were the test substances used to estimate plasma volume, ECFV, and TBW, respectively. Pharmacokinetic analysis of plasma concentration vs time was used to determine changes in body fluid compartments. The pathophysiologic effects of endotoxin were monitored by clinical evaluation, blood chemical changes, and blood gas determinations. All horses became dyspneic with...
Mollett TA, Elmore RG, Blanchard TL, Berg JN.This study was conducted to determine if Escherichia coli endotoxin was absorbed from the equine uterus and if exogenous progesterone and estrogen affected the absorption of intrauterine endotoxin. Six mature anestrous pony mares were used in three consecutive crossover experiments (Periods) with a 14 day recovery between each period. Mares were randomly assigned to one of two treatment groups (three mares per group) and received an intrauterine infusion of either saline or endotoxin. Treatment groups were reversed and readministered after 14 days completing a crossover design (Period 1). Duri...
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...
Templeton CB, Bottoms GD, Fessler JF, Turek JJ, Boon GD.The objectives of this study were to determine the pathophysiological effects of increasing amounts of endotoxin administered intraperitoneally (IP) for 24 hr at which time an intravenous (IV) injection of endotoxin was given. The ability of flunixin meglumine (FM), a nonsteroidal antiinflammatory drug with antiprostaglandin activity, to provide protective effects was also determined. Eight ponies were divided into two groups of four ponies each; one group (untreated) received endotoxin only and the other group (treated) received endotoxin while being treated with flunixin. Hemodynamic and ser...
Bottoms GD, Johnson MA, Lamar CH, Fessler JF, Turek JJ.Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...
Ewert KM, Fessler JF, Templeton CB, Bottoms GD, Latshaw HS, Johnson MA.To evaluate the effect of certain drugs on hematologic changes, blood chemical values, and survival in endotoxin shock, anesthetized ponies were given (IV) endotoxin (Escherichia coli O55:B5) and then treated as follows: Group A ponies--given a saline infusion at 5 minutes and at 3 hours after they were given endotoxin; group B ponies--given flunixin meglumine at 5 minutes and at 3, 6, 9, and 24 hours after they were given endotoxin; group C ponies--treated with dexamethasone; and group D ponies--treated with prednisolone at 5 minutes and at 3, 9, and 24 hours after they were given endotoxin. ...
Duncan SG, Reed SM.In horses with large bowel disease, those with circulating endotoxins but no evidence of altered hemostasis had a good prognosis for survival. Those with circulating endotoxins and evidence of altered hemostasis (fibrin degradation products) had a poor prognosis. Portal vein infusion of endotoxins over 24 hours caused hoof discomfort, evidenced by shifting of weight and standing with all 4 feet together, and a decreased hoof temperature. Clinical signs appeared within 30 minutes of initiation of infusion and subsided within 4 hours despite continued infusion. Long-term heparin therapy results ...
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 ...
Thomson M.Three thoroughbred foals were treated with anti-endotoxin hyperimmune serum. The serum was injected into the affected joint spaces. Two of the foals made a complete recovery.
Wilson RC, Moore JN, Eakle N.The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given end...
Moore AB, Roesel OF, Fessler JF, Bottoms GD.The value of naloxone (1 mg/kg of body weight/hr for 4 hrs), a beta-endorphin antagonist, was assessed in the management of endotoxin-induced shock in ponies. Three groups of 5 ponies each were used: controls, ponies given Escherichia coli endotoxin put untreated, and ponies given endotoxin and then treated with naloxone. Endotoxin-induced changes in hemodynamics, blood chemical values, regional blood flow, plasma enzymes, and energy supplies were measured at selected times during the first 6 hours after endotoxin was given. There was no evidence that beta-endorphins released during shock were...
Meyers K, Reed S, Keck M, Clem M, Bayly W.Twenty-three horses with clinical signs of gastrointestinal disease were evaluated once or serially during the course of the disease for the presence or absence of circulating endotoxin-like substances (ET+ or ET-) and whether the horses were negative, positive, or very positive for serum fibrin/fibrinogen degradation products (FDP-, FDP+, or FDP++). In addition, platelet count, activated partial thromboplastin time (APTT), and 1-stage prothrombin time (OSPT) were measured. When examined initially, 5 horses were ET-/FDP-, 8 were ET-/FDP+, 7 were ET+/FDP-, 3 were ET+/FDP+, and none was ET+/FDP+...
Bottoms GD, Templeton CB, Fessler JF, Johnson MA, Roesel OF, Ewert KM, Adams SB.This study had 2 objectives: (i) to correlate plasma thromboxane and prostaglandin I2 (epoprostenol) concentrations with hemodynamic changes occurring in equine endotoxin shock, and (ii) to determine the effects of flunixin meglumine on plasma concentrations of these prostaglandins relative to hemodynamic changes. Shock was induced in 2 groups, each of 4 anesthetized ponies, and in a 3rd group of 2 ponies. Group A ponies were given endotoxin only (and were not treated), and group B ponies were given endotoxin and then treated with flunixin meglumine. Group C ponies were treated with flunixin m...
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...
Fessler JF, Bottoms GD, Roesel OF, Moore AB, Frauenfelder HC, Boon GD.A study was made of flunixin meglumine (FM), an analgesic agent with antiprostaglandin activity, in the management of endotoxin-induced changes in ponies. Three groups of 5 ponies each were used: A--controls, B--nontreated ponies with endotoxin-induced shock, and C--ponies with endotoxin-induced shock treated with FM. Shock was induced in anesthetized ponies with IV injections of Escherichia coli endotoxin. Disruption of glucose homeostasis, insulin levels, hemograms, aerobic metabolism, and cell damage as indicated by plasma enzymes were observed. Treatment with FM (5 minutes) after shock was...
Bottoms GD, Fessler JF, Roesel OF, Moore AB, Frauenfelder HC.A study was made of flunixin meglumine, an analgesic agent with antiinflammatory and antiprostaglandin activity, for the management of endotoxin-induced cardiovascular derangements. Three groups of 5 ponies each were used: controls--group 1; given endotoxin but not treated--group 2; and given endotoxin and treated with flunixin meglumine--group 3. Shock was induced in anesthetized ponies with IV injection of Escherichia coli endotoxin. Hemodynamic changes were monitored, and regional blood flow was determined at 4 different times, using microspheres labeled with 1 of 4 nuclides. There were ext...
Moore JN, White NA, Berg JN, Trim CM, Garner HE.Experimental small intestinal strangulation obstruction was produced in anesthetized ponies. The limulus amoebocyte lysate test demonstrated the presence of endotoxin in the general circulation 60 and 120 minutes following restoration of mesenteric blood flow. Mucosal degeneration, with loss of villus epithelial cells, was demonstrated coincident with endotoxemia. The findings were consistent with an ischemia-mediated alteration in the intestinal barrier to endotoxin.
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...
Burrows GE.The response of the pony to increasing doses of Escherichia coli endotoxin was evaluated using intravenous and intraperitoneal administration models. Marked changes were seen in all parameters measured following endotoxin administration. Leukopenia (neutropenia, lymphopenia) and thrombocytopenia were not dose-dependent. Similarly, elevated plasma fibrinogen and altered glucose concentrations (hyperglycemia and hypoglycemia), pyrexia and increased lactate/pyruvate ratios were apparent at all endotoxin doses but were not dose related. The widely used packed cell volume and capillary refill time,...
Moore JN, Garner HE, Shapland JE, Hatfield DG.Bacterial endotoxin injected intravenously into conscious ponies produced alterations in cardiopulmonary and gastrointestinal function. Specifically, tachypnoea, dyspnoea, hypoxaemia, colic, lactic acidosis and diarrhoea resulted from administration of 10 micrograms/kg Escherichia coli endotoxin. Pretreatment of the ponies with a potent prostaglandin synthetase inhibitor, flunixin meglumine, prevented these ill effects of endotoxin.
Maire U, Genton M, Vitte-Rossignol A.A 16-year-old, French saddlebred horse was referred for examination because of colic signs, diagnosed with incarceration of the jejunum in a mesoduodenic rent, and subsequently treated surgically (with an end-to-end anastomosis of the jejunum and an enterotomy of the pelvic flexure). The horse initially recovered without complications; however, on the following day, it exhibited moderate signs of endotoxemia and severe serosanguineous discharge from the abdominal wound. Abdominal ultrasonography revealed substantial peritoneal effusion, necessitating the placement of an abdominal drain. The bl...
Stadler P, Van Amstel SR.Commercially available Escherichia coli 055: B5 lipopolysaccharide was administered intravenously experimentally at a dosage of 10 micrograms/kg to 2 horses. Various clinical and clinico-pathological parameters were monitored before and after the endotoxin administration. Because of a hopeless prognosis, and for humane reasons, euthanasia was applied on both horses 6 h after administration. Values recorded for the different parameters, including the blood lactate level, were consistent with a lethal condition. It would appear that an intravenous dose of 10 micrograms/kg of endotoxin is potenti...
Kawamura S, Hirayama K, Mitsuoka T.Two chromogenic Limulus amebocyte lysate systems were evaluated for the measurement of endotoxic activity in feces of normal horses. Fecal extracts had neither non-specific nor inhibitory effect on the test reaction, and the two systems with different specificity showed equivalent results. Endotoxic activities in feces of healthy horses averaged 5.7 +/- 2.8 microns/g wet weight. Correlation between the endotoxin levels and the fecal microbial flora could not be determined.
Olenchock SA, Murphy SA, Mull JC, Lewis DM.Various work environments in agriculture naturally contain gram-negative bacteria and their endotoxins, which are heat stable, lipopolysaccharide-protein complexes that are integral parts of the outer membrane of gram-negative bacteria (1). Respiratory exposure to endotoxin-containing dusts has been associated with both an acute decline in pulmonary function (2) and chronic lung disease (3) in cotton dust-exposed subjects. Endotoxins can profoundly affect both humoral and cellular mediation systems in humans and experimental animals (4). One biologically active humoral system that is associate...
Clark ES, Gantley B, Moore JN.The effects of intravenous (iv) infusion of endotoxin for 60 mins at a cumulative dosage of 0.03 micrograms/kg bodyweight on systemic arterial, right atrial and pulmonary arterial pressures, heart rate, cardiac output, and derived pulmonary vascular resistance and total peripheral vascular resistance were compared to the effects of iv infusion of saline solution in four healthy horses. Heart rate was increased significantly after endotoxin infusion, although diastolic arterial pressure, systolic arterial pressure, electronically averaged arterial pressure, cardiac output, total peripheral resi...
Stadler P, van Amstel SR.The results of a study conducted to determine the clinical changes in 4 experimentally-induced cases of endotoxaemia in the horse are reported on. Endotoxaemia was induced by injecting commercially available E. coli 055:B5 lipopolysaccharide intravenously at a dose of 1 microgram kg-1. The parameters that were monitored include general behaviour, rectal temperature, heart rate, respiratory rate and quality, pulse quality, mucous membrane colour, capillary refill time, appearance of the faeces and the presence of laminitis. Increases in rectal temperature, respiratory and heart rate, capillary ...
Townsend M, Fowler B, Aulakh GK, Singh B.Endotoxin-induced diseases cause significant mortality and morbidity in the horse, leading to enormous economic damage to the equine industry. Neutrophils play a critical role in initiating the immune response in the lung. Pattern recognition receptors (PRRs) are programmed to recognize microbial structures unique to pathogens and mount an immune response. Pentraxin 3 (PTX3) is a PRR that is produced at sites of inflammation by many cell types upon stimulation by pro-inflammatory cytokines and agonists, such as endotoxins [also known as lipopolysaccharides (LPS)]. Pentraxin 3 recognizes and bi...
Clark ES, Moore JN.The effects of slow intravenous (i.v.) infusion of a very low dosage of endotoxin (a cumulative dosage of 0.03 microgram/kg bodyweight [bwt] infused over 60 mins) were evaluated in six conscious healthy horses. Duodenal, right ventral colon, and caecal contractions were detected with strain gauge force transducers. Lateral caecal arterial blood flow was measured using transit time ultrasonic blood flow probes. Duodenal contractile activity was not significantly altered by infusion of endotoxin. In contrast, the contractile activity of the right ventral colon 90 and 270 mins after infusion of e...
Olson NC.Effects of endotoxemia on lung water, hemodynamics, and gas exchange were determined in ponies breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused IV at 20 micrograms/kg of body weight for 1 hour followed by 10 micrograms/kg/hr the subsequent 4 hours. By 0.25 hour, endotoxin increased mean pulmonary artery pressure and pulmonary vascular resistance; this was followed by a return to base-line values by 0.5 and 1 hour, respectively. A 2nd increase in pulmonary vascular resistance occurred by 5 hours of endotoxemia. During the last 2 hours of endotoxin infusion, c...
Veenman JN, Dujardint CL, Hoek A, Grootendorst A, Klein WR, Rutten VP.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...
Raisbeck MF, Garner HE, Osweiler GD.Gram negative endotoxins play a contributory role in the syndrome which results from over consumption of carbohydrates by horses and ponies. Since the antibiotic polymyxin B exerts a direct anti-endotoxin effect by chemically modifying the active lipid A moiety of endotoxin, it might be expected to protect horses after carbohydrate overload and provide a new therapeutic and experimental tool for this condition. The present study was undertaken to evaluate the effect of polymyxin B on hemostatic, hemodynamic, acid-base, and clinical aspects of the syndrome resulting from carbohydrate overload. ...
Moore AB, Roesel OF, Fessler JF, Bottoms GD.The value of naloxone (1 mg/kg of body weight/hr for 4 hrs), a beta-endorphin antagonist, was assessed in the management of endotoxin-induced shock in ponies. Three groups of 5 ponies each were used: controls, ponies given Escherichia coli endotoxin put untreated, and ponies given endotoxin and then treated with naloxone. Endotoxin-induced changes in hemodynamics, blood chemical values, regional blood flow, plasma enzymes, and energy supplies were measured at selected times during the first 6 hours after endotoxin was given. There was no evidence that beta-endorphins released during shock were...
Hwang J, Golla V, Metwali N, Thorne PS.Adverse respiratory health effects in the agricultural industry have been linked to particulate endotoxin exposure. However, whether the endotoxin concentration is significantly correlated to the size of the particle remains an open question. To date, limited research has been conducted to assess particulate endotoxin exposures in the agricultural industry in general or the equine industry in particular. A task-based exposure assessment was conducted to characterize the endotoxin levels of inhalable and respirable particles on four Kentucky farms during the summer season. We conducted personal...
Stadler P, van Amstel SR.The results of a study conducted to determine the clinico-pathological changes in 4 experimentally-induced cases of endotoxaemia in the horse are reported on. Endotoxaemia was induced by injecting commercially available E. coli 055:B5 lipopolysaccharide intravenously at a dose of 1 microgram kg-1. The haematocrit, red cell count, total and differential white cell counts, thrombocyte count, prothrombin time, partial thromboplastin time, fibrinogen level, level of fibrin degradation products, arterial acid-base status, serum lactate and blood glucose were determined repeatedly. Changes that occu...
Henry MM, Moore JN.Whole blood re-calcification times were evaluated as a measure of endotoxin-associated coagulopathy in horses. First, the effects of endotoxin concentration and duration of in vitro incubation of citrated whole blood with endotoxin on the whole blood re-calcification time of blood collected from healthy horses were determined. Increasing concentrations or incubation times of endotoxin accelerated the whole blood re-calcification time. This effect was attributed mainly to increased monocyte thromboplastin activity. Second, whole blood re-calcification time, a clotting profile, plasma factor VII...
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...
Spurlock GH, Landry SL, Sams R, McGuirk S, Muir WW.Plasma volume, extracellular fluid volume (ECFV), and total body water (TBW) were measured before and after endotoxin (Escherichia coli) administration in 6 conscious adult horses. Evan's blue dye, sodium thiocyanate, and antipyrine were the test substances used to estimate plasma volume, ECFV, and TBW, respectively. Pharmacokinetic analysis of plasma concentration vs time was used to determine changes in body fluid compartments. The pathophysiologic effects of endotoxin were monitored by clinical evaluation, blood chemical changes, and blood gas determinations. All horses became dyspneic with...
Turek JJ, Lamar CH, Fessler JF, Bottoms GD.An in vitro system of cultured equine endothelial cells was evaluated as a model for endotoxin (ET) exposure in the horse. Primary cell lines from pulmonary vessels and aortas were cultured from tissues of 6 horses. Effects of ET alone with and without serum and in combination with the cyclo-oxygenase inhibitor flunixin meglumine and isolated equine neutrophils were evaluated by transmission electron microscopy. Cells plus serum were incubated with 10, 25, 50, or 100 micrograms of ET/ml of incubation medium for 1, 3, 8, or 24 hours. Cells without serum were cultured for 1 and 3 hours. Flunixin...
Mollett TA, Elmore RG, Blanchard TL, Berg JN.This study was conducted to determine if Escherichia coli endotoxin was absorbed from the equine uterus and if exogenous progesterone and estrogen affected the absorption of intrauterine endotoxin. Six mature anestrous pony mares were used in three consecutive crossover experiments (Periods) with a 14 day recovery between each period. Mares were randomly assigned to one of two treatment groups (three mares per group) and received an intrauterine infusion of either saline or endotoxin. Treatment groups were reversed and readministered after 14 days completing a crossover design (Period 1). Duri...
Dória RGS, Freitas SH, Laskoski LM, Arruda LP, Shimano AC.Surgical site infection of abdominal incisions is an important complication after laparotomy with increased risk of incisional hernia formation in horses. This study aims to evaluate the healing process of abdominal incisions and correlate peritonitis with the occurrence of surgical site infection and incisional hernias. Nine horses underwent standardized laparotomy, intestinal exploration, and induced septic peritonitis. Standardized relaparotomy was performed two (n = 3), four (n = 3), and six (n = 3) months later to evaluate the abdominal cavity for adhesions and to collect the sutured v...
Morris DD, Crowe N, Moore JN.The purpose of this study was to determine if a structurally novel dual inhibitor of arachidonic acid metabolism, SK & F 86002, would inhibit the endotoxin-induced production of tumor necrosis factor (TNF) activity by equine peritoneal macrophages. Equine peritoneal macrophages were variously pretreated for 0, 0.5 and 2 h with SK & F 86002 at 10(-9) to 10(-4) molar final concentrations or were left untreated. Then, the macrophages were cultured in vitro in the presence of endotoxin (5 ng/mL). Supernatant media were collected after 4 h and stored at -70 degrees C until assayed for TNF a...
Doherty TJ, Andrews FM, Blackford JT, Rohrbach BW, Sandin A, Saxton AM.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...
Janicke H, Taylor PM, Bryant CE.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...
Clark ES, Collatos C.The effects of intravenous infusion of endotoxin for 30 minutes at a cumulative dosage of 0.03 micrograms/kg on average carotid arterial pressure, and on average arterial pressure, capillary pressure, venous pressure, total vascular resistance, precapillary resistance, postcapillary resistance, and capillary filtration coefficient in the jejunum were compared to the effects of intravenous infusion of 0.9% sodium chloride solution in 6 anesthetized horses. Endotoxin significantly reduced intestinal venous blood flow by inducing vasoconstriction. Increased vascular resistance resulted from incre...
Olson NC, Meyer RE, Anderson DL.The effects of endotoxemia on cardiopulmonary parameters, before and after cyclooxygenase blockade, were determined in anesthetized ponies spontaneously breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT), and these were followed by a return to base-line values by 30 min. A second increase in PVR occurred by 5 h ...
Smit LA, Wouters IM, Heederik D, Douwes J.Endotoxins are cell-wall components of Gram-negative bacteria that are commonly present in plants and plant products and in faecal matter. This review presents an overview of endotoxin exposure levels, associated health effects, and relevance regarding veterinary practice. Exposure to airborne endotoxin is especially high in the agricultural sector and among veterinarians, and in particular among those working with horses or farm animals. Inhalation of endotoxins may cause acute airway inflammation and respiratory symptoms that can lead to (non-allergic) asthma and chronic obstructive pulmonar...
Tesfaigzi Y.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...
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 ...
Zizzadoro C, Caruso M, Putignano C, Crescenzo G, Ormas P, Belloli C.The effects of endotoxin on β-adrenergic-mediated relaxation were investigated in the equine digital artery (EDA). Possible involvement of cyclooxygenase-2 (COX-2) in endotoxin-induced effects and basal EDA β-adrenoceptor functionality was also evaluated. Endothelium-intact (e(+)) and/or -denuded (e(-)) EDA rings were incubated overnight with lipopolysaccharide (LPS), LPS+NS398 (selective COX-2 inhibitor) or NS398 alone. Vessel rings were then mounted in organ baths and relaxant responses to isoproterenol (ISOP) recorded on U44069-induced pre-contraction. Response to ISOP was further evaluat...
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...
