Acute abdominal dehiscence following laparotomy: A multicentre, international retrospective study.

BACKGROUND: Incisional complications are a common cause of morbidity following laparotomy. Although uncommon, acute abdominal dehiscence (AAD) is a potentially fatal post-operative complication. However, few AAD cases are described in the literature. OBJECTIVES: To describe common features of cases of AAD following ventral midline laparotomy, management and outcomes. STUDY DESIGN: Retrospective case series. METHODS: Hospital records of horses that underwent a ventral midline laparotomy at nine hospitals in the UK, Ireland and USA over a 10-year period (2009-2019) were reviewed. Data were collected for pre-, intra- and post-operative factors that were considered relevant. Descriptive statistical analysis was performed. RESULTS: A total of 63 cases of AAD were identified. AAD occurred due to tearing of sutures through the linea alba or rupture of the body wall adjacent to the suture line in 46 horses (73%). AAD occurred at a median of 5 days (0.5-70 days) post-operatively and broodmares accounted for 25% of the cases (n = 16). Surgical site infection developed prior to AAD in 28 horses (44%); leakage of peritoneal fluid occurred in 5% of horses prior to AAD being identified. Surgical repair was performed in 27 horses (43%), 10 (16%) were treated conservatively and 26 (41%) were euthanised immediately. Repair was most frequently performed using suture (n = 14), wire (n = 5) or a combination (n = 5). Overall survival to hospital discharge was 39% (24/63). Where surgical repair was performed, 15 horses (56%) survived to hospital discharge; 9 horses (90%) managed conservatively survived to hospital discharge. MAIN LIMITATIONS: Follow-up was not performed for all cases following hospital discharge and some data were incompletely recorded in hospital files. CONCLUSIONS: Previously stated causative factors for AAD were not consistent features in the present study. Surgical site infection following laparotomy and pregnant or early post-partum mares may be important risk factors for AAD and warrant further investigation.

Catheter-associated venous air embolism in hospitalized horses: 32 cases.

BACKGROUND: Venous air embolism is a potentially life-threatening complication of IV catheter use in horses. Despite widespread anecdotal reports of their occurrence, few cases have been reported in the literature and the prognosis is currently unknown. HYPOTHESIS/OBJECTIVES: Our objective was to describe the surrounding circumstances, clinical signs, treatment, progression, and outcome of venous air embolism in hospitalized horses. ANIMALS: Thirty-two horses with acute onset of compatible clinical signs associated with IV catheter disconnection or damage. METHODS: Multicenter retrospective study. Data extracted from clinical records included signalment, presenting complaint, catheter details, clinical signs, treatments, and outcome. RESULTS: Most cases resulted from extension set disconnection occurring within approximately 24 hours after catheter placement. In fewer horses, extension set damage was cited as a cause. Common clinical signs included tachycardia, tachypnea, recumbency, muscle fasciculations and agitation, with abnormal behavior including kicking and flank biting. Less commonly, pathological arrhythmias or more severe neurologic signs, including blindness and seizures, were noted. Progression was unpredictable, with some affected horses developing delayed-onset neurologic signs. Mortality was 6/32 (19%), including 2 cases of sudden death and other horses euthanized because of persistent neurologic deficits. Negative outcomes were more common in horses with recorded blindness, sweating or recumbency, but blindness resolved in 5/8 affected horses. CONCLUSIONS AND CLINICAL IMPORTANCE: The prognosis for resolution of clinical signs after air embolism is fair, but permanent neurologic deficits or pathologic cardiac arrhythmias can arise. Unpredictable progression warrants close monitoring. Systematic clinic-based surveillance could provide additional useful information to aid prevention.

The effect of free and carrier-bound cortisol on equine neutrophil function.

Cortisol is a key anti-inflammatory hormone that increases in bacterial sepsis and circulates predominantly bound to cortisol binding globulin (CBG). Only unbound cortisol was believed to be biologically active, but recent evidence suggests that CBG-bound cortisol also regulates inflammation. The objective of this study was to evaluate the effects of free and CBG-bound cortisol on equine neutrophil function ex vivo. We hypothesized that CBG would enhance cortisol-mediated suppression of neutrophil pro-inflammatory responses. Neutrophils isolated from 8 foals and 6 adult horses were exposed to Staphylococcus aureus antigen (SAA) alone and with hydrocortisone (HC), CBG, or both (CBG+HC). Inflammatory cytokine (TNF-α, IL-8) and reactive oxygen species (ROS) production were measured and compared among stimulants and between ages with linear mixed-effects models. CBG and CBG+HC inhibited ROS production induced by SAA in both foal and horse neutrophils, maintaining it at levels comparable to baseline production (P≤0.060-0.907). TNF-α production was not significantly different among stimulants (P=0.284). CBG+HC significantly (P≤0.016) increased IL-8 production by neutrophils in response to SAA in both foals and adults, although the response of foals was significantly greater than that of adults (P<0.001). These findings suggest that CBG directly modulates equine neutrophil responses, but the effects are cytokine- and age-specific.

Heart rate variability in horses with acute gastrointestinal disease requiring exploratory laparotomy.

OBJECTIVE: To describe heart rate variability (HRV) in horses with acute gastrointestinal disease that undergo exploratory laparotomy. We hypothesized that horses with ischemic gastrointestinal disease will have reduced HRV compared to horses with nonischemic lesions. We further hypothesized that a reduction in HRV will be associated with nonsurvival. DESIGN: Prospective, clinical, observational study. SETTING: University veterinary teaching hospital. ANIMALS: Horses presented for acute colic (n = 57) or elective surgical procedures (n = 10) were enrolled. INTERVENTIONS: Admission heart rate (HR) was recorded and within 2 hours of recovery from general anesthesia continuous telemetry was placed, monitored and recorded for 48-52 hours postoperatively. Stored electrocardiograms were manually inspected and R-to-R intervals were extracted and uploaded into HRV software for analysis. Time domain and frequency spectral analysis were investigated at Times 1 (2-10 h), 2 (16-24 h), 3 (30-38 h), and 4 (44-52 h) postoperatively. A two-way ANOVA for repeated measures was used for group comparisons. Logistic regression analysis was used to detect potential associations between admission HR, time and frequency domain variables, and nonsurvival. MEASUREMENTS AND MAIN RESULTS: Horses diagnosed with an ischemic gastrointestinal lesion (n = 22) at the time of surgery had significantly higher postoperative heart rates and reduced time domain-derived measures of HRV than horses with nonischemic gastrointestinal lesions (n = 35) or control horses (n = 10). Horses that survived to discharge had significantly lower postoperative HRs, higher time domain, and lower low frequency spectral measures of HRV compared to nonsurvivors. The multivariable logistic regression model had a receiver operating characteristic area under the curve (AUC) of 0.95 and was significantly better at predicting nonsurvival than admission HR (P = 0.0124). CONCLUSIONS: Reduced HRV was strongly associated with ischemic gastrointestinal disease and nonsurvival. HRV analysis is a noninvasive technique that may provide diagnostic and prognostic information pertinent to the management of postoperative horses with severe gastrointestinal disease.

Effect of firocoxib on cyclooxygenase 2, microsomal prostaglandin E2 synthase 1, and cytosolic phospholipase A2 gene expression in equine mononuclear cells.

OBJECTIVE: To validate primer sets for use in reverse transcription quantitative PCR assays to measure gene expression of cytosolic phospholipase A2 (cPLA2) and microsomal prostaglandin E2 synthase 1 (mPGES1) in equine mononuclear cells and determine the effects of firocoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on COX-2, cPLA2, and mPGES1 gene expression following incubation of mononuclear cells with lipopolysaccharide (LPS). ANIMALS: 8 healthy adult horses. PROCEDURES: Peripheral blood mononuclear cells were isolated by density gradient centrifugation and incubated at 37°C with medium alone, firocoxib (100 ng/mL), LPS (1 ng/mL or 1 µg/mL), or combinations of firocoxib and both LPS concentrations. After 4 hours, supernatants were collected and tested for prostaglandin E2 (PGE2) concentration with an enzyme inhibition assay, and gene expression in cell lysates was measured with PCR assays. RESULTS: Primer pairs for cPLA2 and mPGES1 yielded single products on dissociation curve analyses, with mean assay efficiencies of 102% and 100%, respectively. Incubation with firocoxib and LPS significantly decreased PGE2 supernatant concentrations and significantly reduced COX-2 and mPGES1 gene expression, compared with values following incubation with LPS alone. CONCLUSIONS AND CLINICAL RELEVANCE: Primer sets for mPGES1 and cPLA2 gene expression in equine mononuclear cells were successfully validated. Firocoxib significantly decreased LPS-induced COX-2 and mPGES1 expression, suggesting that it may be useful in the control of diseases in which expression of these genes is upregulated.

Diagnosis and management of hypoaldosteronism without hypoadrenocorticism in an alpaca.

CASE DESCRIPTION: Primary hypoaldosteronism without concurrent hypoadrenocorticism was diagnosed in an 8-year-old female alpaca with acute onset of weakness progressing to recumbency within 6 hours after onset. CLINICAL FINDINGS: Hematologic testing at admission revealed profound hyponatremia, hypochloremia, and acidemia with a normal blood potassium concentration. Further diagnostic testing, including an ACTH stimulation test, led to a diagnosis of hypoaldosteronism in conjunction with normal cortisol production. TREATMENT AND OUTCOME: The hembra responded well to i.v. polyionic fluid therapy with sodium supplementation and was managed successfully long term with free access to saline (0.9% NaCl) solution in addition to water ad libitum. CLINICAL RELEVANCE: To our knowledge, this is the first reported case of hypoaldosteronism in an alpaca. Hypoaldosteronism should be considered in alpacas as a possible differential diagnosis for refractory hyponatremia or for hyponatremia in which an underlying etiology is not determined.

Daily endogenous cortisol production and hydrocortisone pharmacokinetics in adult horses and neonatal foals.

OBJECTIVE: To compare daily endogenous cortisol production rate and the pharmacokinetics of an i.v. bolus of hydrocortisone between neonatal foals and adult horses. ANIMALS: 10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses. PROCEDURES: Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered i.v. to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid i.v. bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals. RESULTS: The mean ± SD 24-hour cortisol concentration was significantly lower in foals (20 ± 4 ng/mL) than in horses (26 ± 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 ± 320 ng/kg/d) than in horses (2,140 ± 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 ± 1.11 L/kg) and total body clearance (1.39 ± 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 ± 343 ng/mL) than did horses (0.58 ± 0.15 L/kg, 0.349 ± 0.065 L/kg/h, and 8,934 ± 3,843 ng/mL, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.

One-stage prothrombin time, activated partial thromboplastin time, thrombin time, fibrin degradation product concentration, and antithrombin activity in healthy adult alpacas.

BACKGROUND: Alpacas are increasingly presented to veterinarians for evaluation and care. Reports of alpaca reference intervals for one-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), concentration of fibrin degradation products (FDP), and antithrombin (AT) activities are scarce or nonexistent. OBJECTIVE: The aim of this study was to determine values for blood coagulation times (PT, aPTT, and TT), FDP concentrations, and AT activities in healthy adult alpacas. METHODS: Of blood samples collected from 35 clinically healthy adult alpacas via jugular venipuncture and placed into sodium citrate and FDP tubes, 29 samples were assayable for coagulation testing. PT, aPTT, and TT were determined by physical (mechanical) clot detection; AT activity was determined using a thrombin-specific chromogenic substrate end-point assay; and FDP concentrations were determined by the slide agglutination method. RESULTS: Median values and ranges (minimum-maximum) were determined for PT (8.7 seconds, 6.6-11.2 seconds), aPTT (17.3 seconds, 11.9-22.5 seconds), TT (10.2 seconds, 5.4-16.0 seconds), and AT activity (123.3%, 104.8-144.2%). The mean concentration of FDP was <8 µg/mL. CONCLUSION: These values for coagulation times, FDP concentration, and AT activity will provide a useful starting point in the diagnostic evaluation of ill adult alpacas.

Adrenocortical insufficiency in horses and foals.

The adrenal cortices produce various steroid hormones that play vital roles in several physiologic processes. Although permanent adrenocortical insufficiency is rare in all species, emerging evidence in both human and equine medicine suggests that transient reversible adrenocortical dysfunction resulting in cortisol insufficiency frequently develops during critical illness. This syndrome is termed relative adrenal insufficiency (RAI) or critical illness-related corticosteroid insufficiency (CIRCI) and can contribute substantially to morbidity and mortality associated with the primary disease. This review discusses the mechanisms, diagnosis, and clinical consequences of adrenocortical insufficiency, with particular focus on the current understanding of RAI/CIRCI in horses and foals.

Effects of low-dose hydrocortisone therapy on immune function in neonatal horses.

Low-dose hydrocortisone (LDHC) therapy modulates inflammatory responses in adults and improves outcomes in some septic adults and neonates, but its immunologic effects have not been evaluated in neonates. The objective of this study was to evaluate effects of LDHC therapy on ex vivo immune function in neonatal horses (foals). We hypothesized that LDHC treatment would dampen proinflammatory responses without impairing neutrophil function. Hydrocortisone (1.3 mg/kg/d i.v.) was administered to foals in a tapering 3.5 d course. Peripheral blood leukocytes were collected from foals before, during, and after hydrocortisone treatment. A separate group of age-matched untreated foals served as controls. Endotoxin-induced peripheral blood mononuclear cell gene expression of inflammatory cytokines was measured by real-time quantitative RT-PCR. Neutrophils were incubated with labeled, killed Staphylococcus aureus or Escherichia coli for assessment of phagocytosis, and with phorbol myristate acetate, zymosan, or endotoxin for measurement of reactive oxygen species (ROS) production. Neutrophil phagocytosis and ROS production were similar in both groups. Foals receiving hydrocortisone had significantly decreased endotoxin-induced expression of TNF-α, IL-6, IL-8, and IL-1ß. These data suggest that this LDHC treatment regimen ameliorates endotoxin-induced proinflammatory cytokine expression in neonatal foals without impairing innate immune responses needed to combat bacterial infection.

Thrombelastography in 26 healthy horses with and without activation by recombinant human tissue factor.

OBJECTIVES: To develop a standardized technique for thrombelastography (TEG) analysis in healthy adult horses, with and without the ex vivo addition of tissue factor (TF) as an activator. To determine reference intervals for TEG parameters in the horse, and to determine if traditional coagulation tests correlate with TEG. DESIGN: Prospective, observational. SETTING: Veterinary teaching hospital. ANIMALS: Twenty-six healthy adult horses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thrombelastography with (TF-TEG) and without (TEG) the addition of TF performed by 4 operators. Coagulation profiles (prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen, antithrombin, and fibrinogen degradation products) were assessed in a subset of horses. Mean values (SD) for TEG parameters in healthy horses were: reaction time (R)=17.0 minutes (3.0 min), K time (K)=5.8 minutes (2.3 min), clotting rate (Ang)=42 degrees (14 degrees ), maximum clot strength (maximum amplitude [MA])=60.3 mm (5.7 mm), CL30=97.0% (2.0%), LY30=0.8% (0.6%), CL60=92% (5.9%), LY60=3.2% (2.5%). Mean values (SD) for TF-TEG parameters were: R-TF=6.6 minutes (1.4 min), K-TF=3.1 minutes (1.0 min), Ang-TF=50.9 degrees (9 degrees ), MA-TF=62.3 mm (5.1 mm), CL30-TF=97.8% (1.6%), LY30-TF=0.6% (0.5%), CL60-TF=90.8% (4.2%), and LY60-TF=3.6% (1.9%). The addition of TF decreased R and K and increased Ang. TF-TEG had a narrower SD for R, K, Ang, CL60 and LY60 compared with TEG. Interoperator differences were reduced by the addition of TF. Regression analysis indicated a positive relationship between MA and fibrinogen concentrations (P=0.02) and R-TF time and prothrombin time (P=0.03). CONCLUSION: TF-TEG using the described protocol may minimize variability in data obtained across institutions or users. However, due to the variability associated with different operators, it is recommended that each laboratory set up individual reference intervals with the personnel who will perform the assay, and that the assay protocols and data obtained are compared on a regular basis.

The equine TLR4/MD-2 complex mediates recognition of lipopolysaccharide from Rhodobacter sphaeroides as an agonist.

Lipopolysaccharide (LPS) antagonists inhibit the response of inflammatory cells to LPS, presumably by competitive inhibition, and may be of therapeutic value in the treatment of endotoxemia and sepsis. The inhibitory effects of some LPS antagonists are restricted to certain host species, however, as the same molecules can have significant endotoxic activity in other species. This species-specific recognition appears to be mediated by Toll-like receptor 4 (TLR4) and/or MD-2. We have shown previously that LPS from Rhodobacter sphaeroides ( RsLPS) is an LPS antagonist in human cells but an agonist (or LPS mimetic) in equine cells. In the present study, HEK293 cells were transfected with combinations of human and equine CD14, TLR4 and MD-2, and incubated with either RsLPS or with LPS from Escherichia coli as an endotoxin control. NF-kappaB activation was measured in a dual luciferase assay as an indicator of cellular activation. Our results indicate that E. colic LPS activated NF-kappaB in cells transfected with all combinations of the three receptor proteins, whereas RsLPS activated NF-kappaB only in cells expressing the single combination of equine TLR4 and equine MD-2. We conclude that the TLR4/MD-2 complex is responsible for recognition of RsLPS as an agonist in equine cells.

Red maple (Acer rubrum) leaf toxicosis in horses: a retrospective study of 32 cases.

BACKGROUND: Ingestion of wilted red maple leaves by horses can result in severe hemolytic anemia and methemoglobinemia. Little is known about what factors influence the outcome of red maple leaf toxicosis in horses. HYPOTHESIS: Our hypothesis was that physical examination findings, clinicopathologic variables or therapeutic modalities may predict outcome in horses with red maple leaf toxicity. ANIMALS: Horses with red maple leaf toxicosis presented to referral hospitals in the southeast region of the United States. METHODS: A multi-institutional retrospective study was designed to identify factors that predict mortality in horses with red maple toxicosis. RESULTS: Thirty-two horses with red maple toxicosis were identified, 19 of which died. Twenty-nine horses presented with anemia and 24 had clinicopathologic evidence of systemic inflammation. Renal insufficiency was identified in 12/30 (41%) horses. Laminitis (9/28) and colic (13/30) also were identified in horses with red maple toxicosis, but development of these 2 conditions did not have a negative effect on short-term survival. Horses with red maple toxicosis that survived to discharge were likely to have developed pyrexia during hospitalization (P = .030). Horses that were treated with a corticosteroid had a significantly increased likelihood of death (P = .045). There was no significant relationship between initial serum hemoglobin concentration, methemoglobin concentration, or percentage methemoglobin and mortality in this horse series. CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that information obtained on initial examination cannot be used to accurately predict survival in horses with red maple toxicosis, but horses that receive corticosteroids are unlikely to survive.

Concentrations of serum amyloid A and lipopolysaccharide-binding protein in horses with colic.

OBJECTIVE: To determine concentrations of 2 acute-phase proteins (serum amyloid A [SAA] and lipopolysaccharide-binding protein [LBP]) in serum samples obtained from horses with colic and identify relationships among these acute-phase proteins and clinical data. ANIMALS: 765 horses with naturally developing gastrointestinal tract diseases characterized by colic (ie, clinical signs indicative of abdominal pain) and 79 healthy control horses; all horses were examined at 2 university teaching hospitals. PROCEDURE: Serum concentrations of SAA and LBP were determined by immunoturbidometric and dot-blot assays, respectively. RESULTS: SAA and LBP concentrations were determined for 718 and 765 horses with colic, respectively. Concentrations of SAA were significantly higher in nonsurvivors than in survivors, and horses with enteritis or colitis and conditions characterized by chronic inflammation (eg, abdominal abscesses, peritonitis, or rectal tears) had SAA concentrations significantly greater than those for horses with other conditions. Serum concentrations of LBP did not correlate with outcome, disease process, or portion of the gastrointestinal tract affected. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating concentrations of SAA were significantly higher at admission in horses with colic attributable to conditions having a primary inflammatory cause (eg, enteritis, colitis, peritonitis, or abdominal abscesses) and were higher in horses that failed to survive the episode of colic, compared with concentrations in horses that survived. Serum concentrations of LBP did not correlate with survival. Analysis of these findings suggests that evaluation of SAA concentrations may be of use in identifying horses with colic attributable to diseases that have inflammation as a primary component of pathogenesis.

Body weight, hematologic findings, and serum and plasma biochemical findings of horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions.

OBJECTIVE: To compare physiologic, hematologic, and selected serum and plasma biochemical variables obtained from horses competing in 48-, 83-, or 159-km endurance rides before competition and at the same cumulative distance points. ANIMALS: 83 horses. PROCEDURE: Weight and rectal temperature measurements and blood samples were obtained from horses before, during, and after 1 of 3 rides conducted on the same day. Plasma protein (PP), lactate, WBC, serum electrolyte, and calcium concentrations; PCV; and creatine kinase (CK) activity were determined. Assessments were made to determine whether any differences among groups, with respect to total distance competed, could be explained by differences in lap speed or conditioning and to investigate the effect of time in transit or on-site prior to competition on results of blood analyses or competition outcome. RESULTS: Horses in the 159-km distance group had the lowest preride serum sodium, chloride, bicarbonate, and calcium concentrations. As hours in transit increased, preride PP concentration was significantly greater; serum sodium, chloride, and bicarbonate concentrations were lower; CK activity at 159 km was greater; and horses were more likely to be eliminated. The preride sodium was significantly greater in horses that completed the ride, compared with those eliminated. CONCLUSIONS AND CLINICAL RELEVANCE: Among distance groups, distance ridden, speed, level of fitness, and years of experience of horses had little effect on the variables examined. Electrolyte and water supplementation and earlier arrival at the event may be beneficial for horses that are transported long distances to endurance competition.

Effects on plasma endotoxin and eicosanoid concentrations and serum cytokine activities in horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions.

OBJECTIVE: 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. ANIMAL: 3 horses. PROCEDURE: 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) activities; WBC, plasma protein, lactate, serum electrolyte, and calcium concentrations; PCV; and creatine kinase activity. RESULTS: Detection of plasma endotoxin increased during exercise for horses competing at all distances but occurred more frequently in the 48- and 83-km groups. Plasma lactate concentration was significantly greater when endotoxin was concurrently detected. Endotoxin in plasma was not significantly associated with success of race completion. Plasma TxB2 and PGF1alpha concentrations and serum IL-6 activity significantly increased with exercise. Horses that had an excellent fitness level (as perceived by their owners) had greater decreases in serum antiendotoxin antibody titers during exercise than did horses perceived as less fit. In horses with better finish times, TxB2 and PGF1alpha concentrations were significantly greater and TNFalpha activity was significantly less than that of slower horses. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxemia developed during endurance racing, but was significantly correlated with increased plasma lactate concentration and not with other variables indicative of endotoxemia. Plasma TxB2 and PGF1alpha concentrations and serum TNFalpha activity may be associated with performance success.

Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells.

Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaeroides (RsLPS) on equine whole blood and isolated monocyte preparations was investigated by comparing tumor necrosis factor (TNF) production in response to RsLPS and Escherichia coli O55:B5 LPS. Our results indicate that RsLPS is a potent agonist in equine cells, which precludes therapeutic use of this agent in equine patients. In contrast to the results in equine cells, RsLPS did not elicit TNF production by itself, and inhibited the response to E. coli O55:B5 LPS in a human monocytic cell line.

Rhizobium sin-1 lipopolysaccharide (LPS) prevents enteric LPS-induced cytokine production.

Endotoxin (lipopolysaccharide (LPS)), a component of Gram-negative bacteria, is among the most potent proinflammatory substances known. The lipid-A region of this molecule initiates the production of multiple host-derived inflammatory mediators, including cytokines (e.g. tumor necrosis factor-alpha (TNFalpha)). It has been a continuous effort to identify methods of interfering with the interaction between enteric LPS and inflammatory cells using natural and synthetic LPS analogs. Some of these LPS analogs (e.g. Rhodobacter spheroides LPS/lipid-A derivatives) are antagonists in human cells but act as potent agonists with cells of other species. Data reported here indicate that structurally novel LPS from symbiotic, nitrogen-fixing bacteria found in association with the root nodules of legumes do not stimulate human monocytes to produce TNFalpha. Furthermore, LPS from one of these symbiotic bacterial species, Rhizobium sp. Sin-1, significantly inhibits the synthesis of TNFalpha by human cells incubated with Escherichia coli LPS. Rhizobium Sin-1 LPS exerts these effects by competing with E. coli LPS for binding to LPS-binding protein and by directly competing with E. coli LPS for binding to human monocytes. Rhizobial lipid-A differs significantly from previously characterized lipid-A analogs in phosphate content, fatty acid acylation patterns, and carbohydrate backbone. These structural differences define the rhizobial lipid-A compounds as a potentially novel class of LPS antagonists that might well serve as therapeutic agents for the treatment of Gram-negative sepsis.