Plasma L-lactate Research Articles

Comparison of plasma l-lactate between jugular and cephalic veins in healthy and systemically ill horses using a point-of-care device.

To compare plasma l-lactate (LAC) values between samples collected from jugular and cephalic venipuncture in healthy horses and systemically ill horses. Prospective, experimental study. Large animal university teaching hospital. Thirty healthy adult university-owned horses and 43 client-owned horses presenting to the large animal hospital for elective surgical procedures or for emergent medical evaluation of systemic illness. Blood samples were collected from the jugular vein (JV) and cephalic vein (CV) and placed in EDTA blood tubes prior to any medical therapy. LAC values were obtained with a handheld lactate meter at the time of blood collection. LAC was higher in CV samples than JV samples in healthy horses (P<0.001); however, all values were within the normal reference range. Similarly, LAC was higher in CV samples than JV samples in systemically ill horses (P<0.001), but the median JV value was within normal reference range (1.9mmol/L [17.1mg/dL]), while the median CV value was outside the normal reference range (2.9mmol/L [26.1mg/dL]). The CV is an alternative venipuncture site for assessing plasma LAC if the JV is not accessible or to preserve the JV for subsequent catheterization. However, in ill horses, the CV value may be outside the reference range when the corresponding JV value would have been within the reference range.

Serum amyloid A does not predict non-survival in hospitalised adult horses with acute colitis.

Predicting non-survival in horses with acute colitis improves early decision making. Therefore,thisstudyaimed to determine theprognostic value of serum amyloid A (SAA) and other clinicopathological and clinical variables in adult horses with acute colitis. Clinical variables, SAA and other blood biomarkers, including plasma L-lactate (lactate), were assessed in 176 horses with acute colitis. A multivariate model for the prediction of non-survival was constructed. Icelandic horses were analysed separately. Admission SAA was similar in survivors (median 548mg/L; range 0-5453mg/L) and non-survivors (396mg/L; 0-5294) (p = 0.43). A model for non-survival included year of admission, lactate, heart rate, age and colic durationofmore than 24hours. Icelandic horses had a relative risk of 2.9 (95% confidence interval = 2.2-3.8) for acute colitis compared to other breeds. Lactate in Icelandic horses was higher than that in other breeds in both survivors (4.0mmol/L, range 1.0-12.7 vs. 2.0, 0.7-12.5) and non-survivors (10.0, 1.5-26 vs. 5.4, 0.8-22) (p < 0.001). The prognostic value of repeated measurements of SAA could not be assessed in this study, as 71% of the non-surviving horses died within a day of admission. Admission SAA did not predict non-survival. Breed needs consideration when lactate is evaluated as a predictor for non-survival in horses with colitis.

EVALUATION OF THE EFFICACY OF DIFFERENT RUMEN BUFFERS ON PREVENTION OF RUMINAL ACIDOSIS IN GOATS

This study was realized to evaluate the efficacy of dietary supplementation of sodium bicarbonate plus magnesium oxide "MgO", calcareous marine algae (AcidBuf) and essential oils (Actifor®Boost) on the animal performance and prevention of ruminal acidosis in goats moreover, evaluation the diagnostic accuracy of some biochemical parameters including blood pH, total antioxidant capacity (TAC), bicarbonate (HCO3-), partial pressure of carbon dioxide (pCO2), beta-hydroxybutyric acid (βHBA) and plasma L-lactate versus ruminal pH in diagnosis of ruminal acidosis. A total of 30 goats were divided into five equal groups (G1-5) according to the type of dietary treatment. G1 served as a control group and fed the concentrate diet only, G2 fed the concentrate diet supplemented with 10 g Na bicarbonate plus 4g MgO, G3 supplemented with 4g AcidBuf, G4 supplemented with 10 g Na bicarbonate plus 4g MgO plus 4g AcidBuf and G5 supplemented with 1g Actifor® boost/head/day for five days. Tachycardia, tachypnea and decreased ruminal motility were recorded in G1 only. The ruminal pH tended to return to its toward normal for G3 and G4 with a mean of (6.3±0.03 and 6.3±0.01, respectively) which significantly higher than those of G1 and G2 (6.19±0.01 and 6.17±0.02 respectively). A significant increase in plasma L-lactate and a significant decrease in blood pH, HCO3-, pCO2, TAC, and βHBA were recorded in G1 when compared with other groups. Calcareous marine algae with or without adding other compounds found to be a promising rumen buffer agent, moreover TAC and plasma L-lactate showed better diagnostic performance versus rumen pH in the diagnosis of ruminal acidosis.

Acid-base imbalances and the association of blood-gas variables, electrolytes, and biochemical analytes with outcome in hospitalized calves undergoing abdominal surgery.

Surgical abdominal emergencies in calves are associated with a guarded prognosis and have the potential for complex metabolic derangements including acid-base imbalances. To perform a comprehensive analysis of acid-base status and to assess the prognostic relevance of preoperative clinicopathologic variables in calves undergoing abdominal surgery. Hospital-based study samples of 535 (dataset 1; DS1) and 83 calves (dataset 2; DS2). Retrospective (DS1) and prospective (DS2) case series. In DS1, acidemia (pH <7.33) was present in 49.9%, whereas alkalemia (pH >7.37) was present in 30.7% of calves. Plasma L-lactate, chloride, and serum inorganic phosphorus concentration accounted for 51.9%, 11.6% and 9.4% of the variation of venous blood pH, respectively. Classification tree analysis indicated that a negative outcome (death or euthanasia during hospitalization) was associated with venous pO2 ≤33.6 mm Hg, anion gap >18.3 and >22.9mEq/L, serum albumin concentration ≤36.5 and ≤29.4g/L, serum urea concentration >4.4 mmol/L, and plasma ionized calcium concentration ≤1.26 mmol/L. The area under the receiver operating characteristic curve of this model was 0.85 (95% CI: 0.82-0.89, P < .001) and the resulting sensitivity and specificity for the prediction of nonsurvival at the optimal probability cut-point of 0.5 was 89.8% and 65.7%, respectively. In DS2 the model had a similar sensitivity and specificity of 90.5% and 70%, respectively. Clinicopathologic imbalances and associated changes of acid-base status are common in calves with surgical abdominal emergencies and have clinical utility for the prediction of a negative postoperative outcome.

Indicadores clínicos e laboratoriais preditivos do desfecho negativo de emergências gastrointestinais em bovino

Abstract This study aimed to identify clinical and laboratory variables that could help predict the negative outcome in cattle affected by gastrointestinal emergencies. A retrospective cohort study was carried out using multivariate logistic regression analysis based on data collected from the clinical records of cattle hospitalized at the Garanhuns Bovine Clinic, UFRPE campus. One hundred and twenty-two cattle met the inclusion criteria established for the study. Among the clinical variables, heart rate (HR) and abdominal distension are associated with the outcome in animals with right displaced abomasum (RDA), and anorexia and 10% dehydration in animals with an obstructive intestinal disorder. Among the laboratory variables, plasma fibrinogen (PF) and total leukocyte count were associated with the outcome in animals with RDA, while PF and plasma L-lactate were associated with animals with an obstructive intestinal disorder. HR and the total leukocyte count remained in the final model of the regression adjusted for animals with RDA. On the other hand, plasma L-lactate and PF remained in the final model in the adjusted model for animals with an obstructive intestinal disorder. Cattle with RDA and HR higher than 90 bpm present an increased chance of having a negative outcome whereas cattle with obstructive intestinal disorder and plasma L-lactate higher than 1.84 mmol/L or PF higher than 850 mg/dL have a higher chance of not survive. Therefore, clinical and laboratory variables such as HR, fibrinogen, and plasma L-lactate are useful to predict the negative outcome in cattle with gastrointestinal emergencies, especially RDA and obstructive intestinal disorders.

Moderate l-lactate administration suppresses adipose tissue macrophage M1 polarization to alleviate obesity-associated insulin resistance

As a crucial metabolic intermediate, l-lactate is involved in redox balance, energy balance, and acid–base balance in organisms. Moderate exercise training transiently elevates plasma l-lactate levels and ameliorates obesity-associated type 2 diabetes. However, whether moderate l-lactate administration improves obesity-associated insulin resistance remains unclear. In this study, we defined 800 mg/kg/day as the dose of moderate l-lactate administration. In mice fed with a high-fat diet (HFD), moderate l-lactate administration for 12 weeks was shown to alleviate weight gain, fat accumulation, and insulin resistance. Along with the phenotype alterations, white adipose tissue thermogenesis was also found to be elevated in HFD-fed mice. Meanwhile, moderate l-lactate administration suppressed the infiltration and proinflammatory M1 polarization of adipose tissue macrophages (ATMs) in HFD-fed mice. Furthermore, l-lactate treatment suppressed the lipopolysaccharide-induced M1 polarization of bone marrow–derived macrophages (BMDMs). l-lactate can bind to the surface receptor GPR132, which typically drives the downstream cAMP–PKA signaling. As a nutrient sensor, AMP-activated protein kinase (AMPK) critically controls macrophage inflammatory signaling and phenotype. Thus, utilizing inhibitors of the kinases PKA and AMPK as well as siRNA against GPR132, we demonstrated that GPR132–PKA–AMPKα1 signaling mediated the suppression caused by l-lactate treatment on BMDM M1 polarization. Finally, l-lactate addition remarkably resisted the impairment of lipopolysaccharide-treated BMDM conditional media on adipocyte insulin sensitivity. In summary, moderate l-lactate administration suppresses ATM proinflammatory M1 polarization through activation of the GPR132–PKA–AMPKα1 signaling pathway to improve insulin resistance in HFD-fed mice, suggesting a new therapeutic and interventional approach to obesity-associated type 2 diabetes.

Additive prognostic value of preoperative plasma glucose concentrations in calves undergoing abdominal surgery

Surgical abdominal emergencies in calves are associated with a guarded prognosis, especially if neonates are affected. Because hypoglycemia has been associated with sepsis and endotoxemia, this study aimed to assess the prognostic relevance of preoperative plasma glucose concentrations (GLUC) in calves requiring surgery for an acute abdominal disorder. For this purpose, data from retrospective and prospective case series were analyzed, consisting of 586 and 83 hospitalized calves, respectively. The outcomes of calves were evaluated until hospital discharge (both study populations) and for 3 mo following discharge by a phone call to the farmer (prospective study population). For the retrospective study population, the overall survival rate was 31.2%. Calves with a negative outcome (NO) had significantly lower median GLUC (4.3 mmol/L) than calves with a positive outcome (PO; 5.0 mmol/L). The survival rates of calves with GLUC <2.4 mmol/L and 2.4 to 3.1 mmol/L were 3.6 and 8.3%, respectively. The inclusion of GLUC improved a previous prognostic model based on plasma l-lactate concentration and age. The resulting analyses indicated that NO was associated with low age (<7 d), hyper-l-lactatemia (>8.84 mmol/L), and GLUC <4.4 mmol/L (age 7–20 d) and <3.3 mmol/L (age ≥21 d), respectively. The area under the receiver operating characteristic curve of this model was 0.79 (95% confidence interval: 0.76–0.83) and the resulting sensitivity and specificity for NO at the optimal probability cut-point of 0.69 were 66.7 and 85.8%, respectively. For the prospective study population, the established model had sensitivity and specificity for predicting NO after 3 mo (proportion 24%) of 61.9 and 85%, respectively. In both study populations, hypoglycemia was significantly associated with intraoperative evidence of a septic process within the abdominal cavity. The present analyses show that hypoglycemia was highly indicative of a poor prognosis and serious intraoperative findings such as peritonitis. Determination of GLUC should therefore be part of the diagnostic work-up in calves suffering from an acute abdominal emergency.

Prognostic utility of pre- and postoperative plasma l-lactate measurements in hospitalized cows with acute abdominal emergencies

The aim of the present analyses was to compare the prognostic value of pre- and postoperative l-lactate measurements in hospitalized cows requiring surgical intervention for an acute abdominal emergency, such as gastrointestinal ileus or peritonitis. For this purpose, we analyzed data from retro- and prospective case series, consisting of 754 and 98 cows, respectively. Plasma l-lactate concentrations (L-LAC) were determined upon admission to the hospital (both study populations), immediately before initiation of surgical intervention (prospective study population), and 6, 12, 24, 48, and 72 h later (prospective study population). The outcome of cows was evaluated until hospital discharge (both study populations) and 3 mo after discharge by a phone call to the farmer (prospective study population). A negative outcome was defined as death or euthanasia during hospitalization, or if discharged animals had an unsatisfied owner or were culled for medical reasons that were directly related to the initial abdominal emergency. For the retrospective study population, the overall survival rate until hospital discharge was 66%. Cows with a negative outcome (median: 6.81 mmol/L) had significantly higher L-LAC than cows with a positive outcome (3.66 mmol/L) of therapy. At the individual diagnosis level, L-LAC was associated with mortality in cows with a diagnosis of abomasal volvulus, local peritonitis, hemorrhagic bowel syndrome, and jejunal volvulus. Considering the whole study population, the area under the receiver operating characteristic curve was 0.66. For the prospective study population, the proportion of cows with a positive outcome was 65% until hospital discharge and 61% after the 3-mo observation period. At all sampling times, before and during the first 12 h after surgical intervention, cows with a negative outcome had significantly higher L-LAC than cows with a positive outcome. The largest area under the receiver operating characteristic curve for L-LAC was observed at 6 h (0.89). A cut-point of 1.77 mmol/L was identified, which had a sensitivity and specificity for predicting a negative outcome until hospital discharge of 88.9 and 73.4%, respectively. The present analyses confirmed previous findings in calves and show that persistent hyper-l-lactatemia during the early postoperative period is a more reliable indicator for a negative outcome than hyper-l-lactatemia before initiation of surgical intervention.

Postpartum supplementation with fermented ammoniated condensed whey altered nutrient partitioning to support hepatic metabolism

Our previously published paper demonstrated that fermented ammoniated condensed whey (FACW) supplementation improved feed efficiency and metabolic profile in postpartum dairy cows. The objective of this study was to further explore the effects of FACW supplementation on liver triglyceride content, hepatic gene expression and protein abundance, and plasma biomarkers related to liver function, inflammation, and damage. Individually fed multiparous Holstein cows were blocked by calving date and randomly assigned to postpartum (1 to 45 d in milk, DIM) isonitrogenous treatments: control diet (n = 20) or diet supplemented with FACW (2.9% dry matter of diet as GlucoBoost; Fermented Nutrition, Luxemburg, WI, replacing soybean meal; n = 19). Liver biopsies were performed at 14 and 28 DIM for analysis of mRNA expression, protein abundance, and liver triglyceride content. There was marginal evidence for a reduction in liver triglyceride content at 14 DIM in FACW-supplemented cows compared with the control group. Cows supplemented with FACW had greater mRNA expression of glucose-6-phosphatase at 14 DIM relative to control. Supplementation with FACW increased mRNA expression of pyruvate carboxylase (PC), but did not alter cytosolic phosphoenolpyruvate carboxykinase (PCK1), resulting in a 2.4-fold greater PC:PCK1 ratio for FACW-supplemented cows compared with control. There was no evidence for a FACW effect on mRNA expression of propionyl-CoA carboxylase nor on mRNA expression or protein abundance of lactate dehydrogenase A or B. Cows supplemented with FACW had lower plasma urea nitrogen compared with control. Plasma l-lactate was greater for FACW-supplemented cows compared with control at 2 h before feeding time at 21 DIM. There was no evidence for altered expression of IL1B or IL10, or blood biomarkers related to liver function and damage. Greater glucose-6-phosphatase and PC gene expression, together with greater blood glucose and similar milk lactose output, suggests that FACW increased the supply of glucose precursors, resulting in greater gluconeogenesis between 3 and 14 DIM. Greater hepatic PC:PCK1 ratio, together with previously reported decreased plasma β-hydroxybutyrate and the marginal evidence for lower liver triglyceride content at 14 DIM, suggests greater hepatic capacity for complete oxidation of fatty acids in FACW-supplemented cows compared with control. Overall, improvements in metabolite profile and feed efficiency observed with postpartum supplementation of FACW may be attributed to increased gluconeogenic and anaplerotic precursors, most likely propionate, due to modulated rumen fermentation.

Elevated Lactate Levels in Acute Pulmonary Embolism Are Associated with Prothrombotic Fibrin Clot Properties: Contribution of NETs Formation.

Background: Elevated plasma lactate levels correlate with high mortality rate in acute pulmonary embolism (PE) patients. We hypothesized that elevated lactate levels correlate with prothrombotic fibrin clot properties and enhanced neutrophil extracellular trap (NET) formation in acute PE. Methods: As many as 126 normotensive acute PE patients (aged 58 ± 14 years) were enrolled. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), citrullinated histone H3 (citH3), and plasminogen activator inhibitor-1 antigen (PAI-1), together with plasma L-lactate levels were evaluated on admission. Results: Lactate levels ≥2 mM were found in 70 (55.6%) patients in whom we observed 29% higher neutrophil count and 45% elevated plasma citH3 levels. Elevated lactate levels were associated with more prothrombotic fibrin properties as reflected by 11% reduced Ks, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 (p < 0.05). An increase of lactate levels by 1 mM leading to the prolongation of CLT by 8.82 min was shown in the linear regression. Conclusions: Our findings suggest a new mechanism contributing to a negative impact of elevated lactate levels on prognosis in acute PE patients, in particular hypofibrinolysis, associated with enhanced NET formation.

Cardiac, Energy and Hormonal Blood Markers, and Lactatemia in Cows with Displaced Abomasum

Background: Displaced abomasum (DA) is a common and economically important disorder that affects dairy cattle. Nutritional factors and adaptive responses that occur in the peripartum play a central role in the pathogenesis. The measurement of blood metabolites represents a useful tool for monitoring and prognostic determination in affected animals. Therefore, the objective was to evaluate cardiac, energy and hormonal blood markers, lactatemia, and insulin sensitivity in cows diagnosed with right displaced abomasum (RDA) and left displaced abomasum (LDA), comparing them with each other.Materials, Methods &amp; Results: Nineteen cases of abomasum displacement in cows were studied, including 9 cases of RDA and 10 cases of LDA. The diagnosis was established by means of physical examination and measurement of the concentration of chlorides in the ruminal fluid (&gt; 30mEq/L). After diagnosis, clinical-surgical therapeutic management was instituted. At the time of diagnosis (M1) and at the resolution of the case (M2), blood samples were collected to assess the variables: non-esterified fatty acids (NEFA), beta hydroxybutyrate (βHB), L-lactate, creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), glucose, insulin, and cortisol. In addition, insulin sensitivity was estimated using the Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) and RQUICKI-βHB. The means of the variables were compared, separating the effects of groups (RDA and LDA) and moments (M1 and M2), at the level of 5% probability. The concentrations of NEFA, CK-MB, L-lactate, glucose, insulin, and cortisol were higher at M1 and the RQUICKI and RQUICKI-βHB indices were lower at this moment. L-lactate, CK, and CK-MB were higher in the RDA group, while cTnI, βHB, and LDH did not present a group or moment effect. Cardiac markers correlated with the energy profile metabolites, L-lactate, and cortisol.Discussion: The high concentrations of NEFA at M1 reflected the condition of negative energy balance. βHB concentrations were stable, that may be related to the number of days postpartum in which the animals were diagnosed. The hyperglycemic condition and the increase in serum cortisol concentrations found at M1 can be induced by the condition of metabolic stress resulting from the disease. Hyperinsulinemia were recorded in the present study could be an important factor related to the pathogenesis of DA, since there seems to be a correlation between hyperinsulinemia and decreased abomasal emptying rate. The RQUICKI and RQUICKI-βHB indices was significantly lower at M1, which may indicate lower sensitivity of peripheral tissues to insulin at this time. Changes in serum activity of LDH and CK may result from tissue damage due to organ displacement, in addition to damage associated with surgery and the administration of injectable drugs, mainly intramuscularly. The elevation in plasma L-lactate at M1 and in the RDA group may be associated with abomasal hypoperfusion. The high positive correlations found between L-lactate and the variables glucose, insulin, and cortisol reinforcing the association between the concentration of L-lactate and the moment of greatest stress. The increase in cardiac biomarkers may be related to the occurrence of ischemia/reperfusion injury in the abomasum, which involves oxidative stress and the production of inflammatory mediators. The hyperglycemic condition and the higher concentrations of NEFA can also contribute to the occurrence of myocardial injury. The correlations found between cardiac biomarkers and plasma L-lactate, strengthen the idea that there is a relationship between L-lactate and myocardial injury. In this sense, the measurement of blood concentrations of cTnI, CK-MB, and L-lactate could contribute as severity markers and prognosis indicators in cattle with DA.

Prognostic relevance of pre- and postoperative plasma l-lactate measurements in calves with acute abdominal emergencies

In both human and veterinary medicine, l-lactate is a well-established prognostic biomarker of disease severity and mortality and has also attracted increasing attention in bovine medicine due to the availability and validation of cheap and portable l-lactate analyzers. The aim of the present study was to evaluate the prognostic accuracy of plasma L-lactate measurements in calves with acute abdominal emergencies before and during the initial therapeutic period after surgical intervention. A prospective observational study was carried out involving 83 hospitalized calves up to an age of 7 mo, which required surgical intervention for reasons of an acute abdominal emergency such as gastrointestinal ileus or peritonitis. Plasma l-lactate (L-LAC) concentrations were determined immediately before initiation of surgery and 6, 12, 24, 48, and 72 h later. The outcome of calves was evaluated 3 mo after discharge by a phone call to the farmer, and a positive outcome was defined if the calf was still alive and the owner was satisfied with the animal's postsurgical progress. A total of 29% of calves were discharged from the hospital and the proportion of calves with a positive outcome after the 3-mo period was 24%. At all sampling times during the first 48 h after initiation of surgical intervention, calves with a negative outcome had significantly higher L-LAC than calves with a positive outcome. A binary logistic regression analysis indicated that the odds for a negative outcome during the 3-mo observation period increased by a factor of 1.23 [95% confidence interval (CI): 1.04-1.44] for every mmol/L increase of L-LAC before initiation of surgical intervention, but by a factor of 5.29 (95% CI: 1.69-16.6) and 5.92 (95% CI: 1.29-27.3) at 12 and 24 h, respectively. The largest area under the receiver operating characteristic curve for L-LAC was observed at 12 h (0.91; 95% CI: 0.83-0.99), and a cut-point of 2.75 mmol/L was identified that had a sensitivity and specificity for predicting a negative outcome of 68 and 100%, respectively. In conclusion, persistent hyper-l-lactatemia during the early postoperative period is a more reliable indicator for a negative outcome in calves with acute surgical abdominal emergencies than hyper-l-lactatemia before initiation of surgical intervention. Postoperative measurements of L-LAC are therefore a clinically useful tool to identify patients with an increased risk for a negative outcome at an early stage after surgical intervention was carried out.

Relationships between plasma lactate, plasma alanine, genetic variations in lactate transporters and type 2 diabetes in the Japanese population

The present study aimed to characterize the relationships between plasma lactate, plasma alanine, monocarboxylate transporter (MCT) polymorphisms, and indices of diabetes in patients with type 2 diabetes (T2D) in Japan. Eighty-three patients with T2D were prospectively enrolled. The gluconeogenesis and glycogenolysis are enhanced and uptake of glucose is decreased in the T2D liver. Since the liver plays an important role in maintaining glucose metabolism, we examined the relationships between liver enzymes and indices of diabetes. Some studies have reported that MCT1 (SLC16A1) polymorphism causes metabolic diseases. In addition, a high frequency of MCT1 polymorphism was reported in a healthy Japanese population. However, little is known about the relationships between T2D and MCT polymorphisms. Plasma l-lactate concentration positively correlated with indices of diabetes (fasting plasma glucose [FPG] and hemoglobin A1c [HbA1c]) and with the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GTP). MCT1 polymorphisms were associated with all of these markers. We identified no significant correlations between d-lactate or alanine concentrations and any of these markers, but a significant association was observed between l-lactate, a marker of oxidative capacity, and indices of diabetes. We conclude that plasma l-lactate concentration may represent a predictor of the progression or severity of T2D.

Prognostic value of preoperative plasma l-lactate concentrations in calves with acute abdominal emergencies

Acute abdominal emergencies in calves due to abomasal disorders, gastrointestinal ileus, or peritonitis are characterized by a rapid disease progression and usually require immediate surgical intervention. Those conditions are associated with a guarded prognosis, and the aim of the present study was to assess the prognostic relevance of preoperatively measured plasma l-lactate concentrations (l-LAC) in a large study population of calves with a broad spectrum of acute abdominal emergencies. For the purpose of this study, the medical records of 587 calves admitted to a veterinary teaching hospital over a 10-yr period were analyzed retrospectively. Plasma l-LAC was measured as part of a routinely performed biochemistry panel before initiation of surgical intervention. Hyper-l-lactatemia (plasma l-LAC >2.2 mmol/L) was evident in 75% of calves, and the overall survival rate until hospital discharge was 31%. Calves with a negative outcome were younger (median: 3.4 vs. 6 wk) and had higher plasma l-LAC (median: 4.96 vs. 3.09 mmol/L) than calves with a positive outcome. At the individual diagnosis level, l-LAC was associated with mortality in calves with a diagnosis of mesenteric torsion, right-sided dilated abomasum, small intestinal volvulus, or paralytic ileus, but not in calves suffering from peritonitis, malformations, abomasal volvulus, bloat, or small intestinal intussusceptions. Considering the whole study population, the area under the receiver operating characteristic (ROC) curve for plasma l-LAC was 0.66 [95% confidence interval (CI): 0.61-0.70]. A classification tree analysis indicated that l-LAC >8.84 mmol/L and age categories of <3 wk and <1 wk were independent predictors of mortality. The area under the ROC curve of this model was 0.75 (95% CI: 0.71-0.79) and the resulting sensitivity and specificity for the prediction of nonsurvival at the optimal probability cut-point of 0.62 were 67.7 and 76.6%, respectively. In conclusion, hyper-l-lactatemia is common in calves suffering from acute abdominal emergencies. Markedly increased plasma l-LAC is associated with an increased mortality risk, but it is not possible to reliably predict the outcome of affected calves based on a single, preoperative measurement. However, a clinically important finding of this study was that the ability to predict a negative outcome is improved when the age of the calf is considered in addition to plasma l-LAC.

Effect of maltodextrin supplementation on blood glucose, lactate, insulin, and cortisol levels of horses subjected to submaximal incremental exercise test

Riders and trainers believe that oral maltodextrin (MD) supplementation prior to exercise increases blood glucose availability and delay the onset of fatigue in horses, although there is no evidence supporting this claim. Therefore, we aimed to evaluate the effect of MD supplementation on blood glucose, L-lactate, insulin, and cortisol levels and heart rate in horses subjected to an incremental exercise test. A randomized placebo-controlled crossover trial was designed to test the effect of three doses of MD (50 g, 100 g and 200 g) on blood glucose, L-lactate, insulin, and cortisol levels and heart rate of four Purebred Lusitanian geldings. A seven-step incremental field exercise test was used; the initial speed was set at 2.5 m/s, followed by 3.3 m/s, 4.1 m/s, 5.0 m/s, 6.6 m/s, and 8.4 m/s. There was a significant influence of exercise itself on plasma glucose and L-lactate concentrations and on heart rate (p < 0.05), whereas the amount of MD administered changed only the cortisol levels (p < 0.05). During rest and exercise, the variables remained within the normal reference range for stalled and exercising horses, respectively. Blood glucose levels in the placebo group at rest, 5.0 m/s, and 8.4 m/s were 87.63 ± 3.25 mg/dL, 78.33±10.08 mg/dL, and 95.18 ± 14.73 mg/dL, respectively, whereas those for the group supplemented with 200 g MD were 99.25±12.19 mg/dL, 79.55±13.81 mg/dL, and 97.30 ± 16.46 mg/dL, respectively. The mean cortisol levels in the placebo and 200 g MD groups at 8.4 m/s were 1.20 ± 0.53 mmol/L and 5.54 ± 4.73 mmol/L, respectively. In conclusion, MD supplementation increased serum cortisol levels and showed no effect on heart rate, blood glucose, L-lactate and serum insulin levels of horses submitted to an incremental exercise test.

Experimental protocol for metabolic acidosis induction by intravenous administration of hydrochloric acid in sheep

ABSTRACT The aim of this study was to assess the magnitude and duration of blood and urine changes and the side effects of hyperchloremic acidosis induced by the intravenous administration of hydrochloric acid in sheep. Five healthy, crossbred adult ewes, with a mean body weight of 44±2.9kg were used. The hydrochloric acid solution was administered intravenously at a rate of 25mL/kg/h for 4 hours continuously. Venous blood and urine samples were collected and pH values, blood carbon dioxide partial pressure, bicarbonate, base excess, strong ion difference, anion gap, total concentration of nonvolatile buffers, creatinine, plasma L-lactate, plasma and urine sodium, potassium, and chloride were determined. The experimental protocol induced severe hyperchloremic acidosis at the end of the infusion, with a decreased plasma strong ion difference. The fractional excretion of sodium and chloride remained increased during 4 hours after the infusion. Aciduria was observed at approximately 24 hours. Twenty-four hours after the infusion, the animals showed mild and compensated metabolic acidosis. This protocol was effective in inducing severe and long-lasting hyperchloremic acidosis and did not cause serious side effects. Therefore, this protocol can be used safely in adult sheep for studies on the treatment of this condition.

Abstract 5055: Multiplatform metabolomics analysis of growth arrest in pancreatic tumor xenografts

Abstract R,S-4-Methoxy-1-naphthylfenoterol, MNF, inhibits the G protein-coupled receptor GPR55. In this study, we determine the effect of MNF on human PANC-1 pancreatic tumor growth in mice and apply multiplatform metabolomics analysis to identify pathways associated with growth arrest. Methods: Female Balb/c nude mice, 6-8 weeks old, 18-20g, were inoculated subcutaneously with 5 x 106 PANC-1 cells. On Day 8, mice were placed in groups of 10 using random block design based upon tumor volume. Mice received daily ip injections of vehicle or 40mgxkg-1 MNF 5 days/week for 3 treatment cycles. Mice were monitored daily and tumor volumes measured at beginning and end of each dosing cycle. On Day 33, mice were euthanized, and plasma samples and tumors collected. Tumor tissue was homogenized, extracted and analyzed using liquid chromatography-QTOF-MS, capillary electrophoresis-TOF-MS and gas chromatography-EI-Q-MS. Differences between groups were evaluated by unpaired t-test or Mann−Whitney test with post hoc Benjamini-Hochberg correction. Statistical significance was set at P≤0.05. Compound identification was accomplished using online databases and in-house standards Results Tumor volume increased in vehicle-treated mice by ~700%, 142 ± 8 mm3 to 957 ± 79 mm3 and only ~250% in MNF-treated mice, 143 ± 8 mm3 to 259 ± 27 mm3. On Day 33, MNF was not detected in plasma but accumulated in tumor tissues, 43.9 ± 32.7 ng/g. Plasma L-lactate levels were reduced from 3.29 ± 0.66 mmol/L το 2.81 ± 0.60 mmol/L, P≤0.001. Differences in tumor tissue metabolome were observed with MNF compared to vehicle, which was reflected by significant, P≤0.05, changes in relative metabolite signals. MNF treatment was accompanied by the disruption of pyrimidine nucleotide biosynthesis at uridine 5'-monophosphate, UMP, and increased UMP degradation. Moreover, the +237% increase in ophthalmic acid and +95% increase in its precursor 2-aminobutyrate indicate higher oxidative stress and the +51% increase in 2-hydroxyproline suggest greater HFI-1α proteolysis upon MNF treatment. Conclusions These results are consistent with our previous observations in PANC-1 cells showing that GPR55 inhibition attenuates activation of the EGFR-MEK-ERK, Wnt-β-catenin and PI3K/AKT pathways resulting in lower cyclin D1 expression and halting the cell cycle in G1. The reduction in HIF-1α expression and glycolytic flux in MNF-treated PANC-1 cells is in line with the decline in L-lactate plasma levels in MNF-treated mice. The data from this study indicate that MNF may be useful in the treatment of pancreatic cancer. Citation Format: Irving W. Wainer, Danuta Dudzik, Michel Bernier, Coral Barbas. Multiplatform metabolomics analysis of growth arrest in pancreatic tumor xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5055. doi:10.1158/1538-7445.AM2017-5055

Glucose requirements of an activated immune system in lactating Holstein cows

Accurately quantifying activated immune system energy requirements in vivo is difficult, but a better understanding may advance strategies to maximize animal productivity. Study objectives were to estimate whole-body glucose utilization following an i.v. endotoxin challenge. Lactating Holstein cows were jugular catheterized and assigned 1 of 3 bolus treatments: control (CON; 5 mL of saline; n = 6), lipopolysaccharide (LPS)-administered (LPS-C; 1.5 μg/kg of body weight; Escherichia coli 055:B5; n = 6), and LPS + euglycemic clamp (LPS-Eu; 1.5 μg/kg of body weight; 50% glucose solution infusion; n = 6). After LPS administration, blood glucose was determined every 10 min and glucose infusion rates were adjusted in LPS-Eu cows to maintain euglycemia for 720 min. Blood samples were obtained 180, 360, 540, and 720 min postbolus for further analysis. Cows were milked 360 and 720 min postbolus. Blood glucose was increased 84% in LPS-administered cows for up to 150 min postbolus; thereafter, circulating glucose was decreased 30% in LPS-C relative to LPS-Eu and CON cows. Mild hyperthermia (+0.5°C) occurred between 30 and 90 min postbolus in LPS-administered relative to CON cows; thereafter, rectal temperature did not differ between treatments. Milk yield and lactose percentage were decreased 80 and 11%, respectively, in LPS-administered relative to CON cows. Circulating insulin was increased 4 fold and nonesterified fatty acids, β-hydroxybutyrate, and ionized Ca were decreased ∼50% in LPS-administered compared with CON cows. Plasma l-lactate, haptoglobin, and serum amyloid A increased ∼160, 260, and 75%, respectively, in LPS-administered relative to CON cows. Overall, LPS-binding protein was increased 87% in LPS-administered relative to CON cows; however, at 720 min, it was decreased 25% in LPS-Eu compared with LPS-C cows. White blood cell count decreased ∼90% in LPS-administered cows at 180 min and progressively increased to ∼50% of CON values by 720 min. Total glucose deficit during the 720 min following LPS administration was calculated as the decrease in the amount of glucose required to synthesize milk (due to the decrease in milk yield relative to prebolus levels) plus the amount of glucose infused to maintain euglycemia (in LPS-Eu cows only) and was 461, 1,259, and 1,553 g for CON, LPS-C, and LPS-Eu cows, respectively. Our data indicate an acutely activated immune system uses >1 kg of glucose within 720 min and maintaining euglycemia did not rescue milk synthesis.

Reliability of the Lactate Scout point-of-care instrument for the determination of blood L-lactate concentration in sheep.

Data on accuracy and precision of the Lactate Scout point-of-care (POC) analyzer in ovine medicine are lacking. The purpose of the study was to assess the reliability of the Lactate Scout in sheep. Fifty-seven sheep at varying ages with various diseases were included. Blood lactate concentration in samples collected from the jugular vein was measured immediately on the Lactate Scout. Plasma L-lactate concentration was measured by the Cobas autoanalyzer as the reference method. Data were subjected to Student's t-test, Passing-Bablok regression, and Bland-Altman plot analyses for comparison and assessment of accuracy, precision, and reliability. Plasma l-lactate concentration was consistently lower than blood L-lactate concentration (3.06 ± 0.24 vs 3.3 ± 0.3 mmol/L, P < .0001). There was a positive correlation between plasma and blood L-lactate concentrations (r = .98, P < .0001). The Lactate Scout had 99% accuracy and 98% precision with the reference method. Blood (Y) and plasma (X) L-lactate concentrations were fitted to Y = 0.28 + 1.00 · X, with a residual standard deviation of 0.31 and a negligible deviation from the identity line (P = .93). The bias was fitted to Y = 0.10 + 0.05 · X, with Sy.x of 0.44 (P < .07). The Lactate Scout has high accuracy and precision, with a negligible bias. It is a reliable POC analyzer to assess L-lactate concentration in ovine medicine.

Effects of dairy products on intestinal integrity in heat-stressed pigs

Heat stress compromises intestinal integrity which may partially explain its negative effects on animal health and productivity. Research suggests that challenged intestinal barrier function improves with dietary dairy products in various models. Thus, the study objective was to evaluate the effects of bovine milk whey protein (WP) and colostral whey protein (CWP) on intestinal integrity in heat-stressed pigs. Crossbred gilts (39 ± 3 kg body weight) were fed 1 of 4 diets (n = 8 pigs/diet): control (Ct), control diet containing an 80% WP and 20% CWP product (WP80), control diet containing a 98% WP and 2% CWP product (WP98), and control diet containing a 100% WP product (WP100). After 7d on experimental diets, pigs were exposed to constant heat stress conditions (32 °C) for 24h. There were no treatment differences in growth or body temperature indices prior to heat stress. During heat exposure, both rectal temperature and respiration rate increased (+0.85 °C and 3-fold, respectively; P < 0.01), and feed intake and body weight decreased (44% and -0.5kg, respectively; P < 0.01), but neither variable was affected by dietary treatments. Plasma L-lactate and D-lactate concentrations increased (36%; P < 0.01) and tended to increase (19%; P = 0.09) with heat stress. After 24h of heat exposure, WP100-fed pigs had lower plasma D-lactate relative to Ct-fed pigs. Ileal transepithelial electrical resistance was decreased (37%; P = 0.02) in WP80 pigs, compared with controls. No differences were detected in other intestinal integrity ex vivo measurements. These data demonstrate that dietary WP and CWP did not mitigate intestinal integrity dysfunction during severe heat stress.