Anion gap correlates with serum D- and DL-lactate concentration in diarrheic neonatal calves

The objective of this study was to investigate the relationship between serum D- and L-lactate concentrations, and anion gap (AG) in neonatal calves. The association of AG with lactic acidosis in diarrheic calves has only been investigated by measurement of L-lactate in calves with experimentally induced diarrhea. D-lactate has recently been reported to be present in high concentrations in the serum of some diarrheic neonatal calves. The contribution of this acid to AG is not reported. The relationship between AG and L- and D-lactate concentrations was examined in 24 healthy calves and 52 calves with naturally occurring infectious diarrhea with metabolic acidosis. AG was calculated as [Na+ + K+] - [Cl- + HCO3-]. D- and L-lactate were quantified using high-performance liquid chromatography. There was no correlation between L-lactate and AG, contrary to previous reports in the literature. Moderate correlations between D-lactate concentration and AG (r = .74, P < .0001), and between DL-lactate and AG (r = .77), P < .0001) were detected. No differences existed due to the age or sex of the calf. This study indicates that AG provides information on the nature of acidosis in the diarrheic, neonatal calf and reinforces the importance of investigating clinical, in addition to experimental, populations.     

Lactobacillus GG does not affect D-lactic acidosis in diarrheic calves, in a clinical setting

D-lactate, produced by gastrointestinal fermentation, is a major contributor to metabolic acidosis in diarrheic calves. Lactobacillus rhamnosus GG survives gastrointestinal transit in the neonatal calf and does not produce D-lactate. To determine whether this probiotic reduces gastrointestinal D-lactate production or severity of diarrhea or both, 48 calves (mean, 11 days old; range, 2-30 days) admitted to the clinic for treatment of diarrhea were randomly allocated to 2 groups. The experimental group was given Lactobacillus rhamnosus GG (1 x 10(11) cfu/d) PO, dissolved in milk or oral electrolyte solution, in addition to clinic treatment protocols; the other group served as a control. Serum and fecal samples were obtained at admission and at 24 and 48 hours after initial administration of Lactobacillus rhamnosus GG. All samples were analyzed for D- and L-lactate by using high-pressure liquid chromatography. Feces were also analyzed for pathogens, Lactobacillus rhamnosus GG recovery, and dry matter. D-lactic acidemia (>3 mmol/L) was present in 37/48 calves at admission. Lactobacillus rhamnosus GG was recovered in the feces of 13 experimental calves and 0 control calves 24 hours after administration. No difference in serum or fecal D- or L-lactate between the groups was detected at any time point. After therapy, D-lactic acidosis was absent at 48 hours in all but 1 calf. No relation between fecal pathogen (viral, bacterial, or protozoal) and degree of D-lactic acidosis was observed. The reduction in mortality and greater fecal dry matter in Lactobacillus rhamnosus GG-treated calves was not statistically significant.     

The alkalinizing effects of metabolizable bases in the healthy calf.

The alkalinizing effect of citrate, acetate, propionate, gluconate, L and DL-lactate were compared in healthy neonatal calves. The calves were infused for a 3.5 hour period with 150 mmol/L solutions of the sodium salts of the various bases. Blood pH, base excess, and metabolite concentrations were measured and the responses compared with sodium bicarbonate and sodium chloride infusion. D-gluconate and D-lactate had poor alkalinizing abilities and accumulated in blood during infusion suggesting that they are poorly metabolized by the calf. Acetate, L-lactate and propionate had alkalinizing effects similar to bicarbonate, although those of acetate had a slightly better alkalinizing effect than L-lactate. Acetate was more effectively metabolized because blood acetate concentrations were lower than L-lactate concentrations. There was a tendency for a small improvement in metabolism of acetate and lactate with age. Sodium citrate infusion produced signs of hypocalcemia, presumably because it removed ionized calcium from the circulation. D-gluconate, D-lactate and citrate are unsuitable for use as alkalinizing agents in intravenous fluids. Propionate, acetate and L-lactate are all good alkalinizing agents in healthy calves but will not be as effective in situations where tissue metabolism is impaired.     

Influence of D-lactate on metabolic acidosis and on prognosis in neonatal calves with diarrhoea

Three hundred bucket-fed diarrhoeic calves up to the age of 21 days were used to investigate the degree in which D-lactic acid contributes to metabolic acidosis in bucket-fed calves with naturally acquired neonatal diarrhoea. Fifty-five percent of all diarrhoeic calves had serum D-lactate concentrations higher than 3 mmol/l. Mean (+/-SD) D-lactate values were 5.7 mmol/l (+/-5.3, median: 4.1 mmol/l). D-lactate values were distributed over the entire range of detected values from 0 to 17.8 mmol/l in calves with base excess of -10 to -25 mmol/l. Serum D-lactate concentration was higher in patients with ruminal acidosis (6.6 +/- 5.2 mmol/l; median: 5.9 mmol/l) than in those with physiological rumen pH (5.3 +/- 5.4 mmol/l; median: 3.7 mmol/l). There was no evidence of a correlation (r = 0.051) between the serum levels of D-lactate and creatinine (as an indicator of dehydration). D-lactate was correlated significantly with both base excess (r = -0.685) and anion gap (r = 0.647). The proportion of cured patients was not significantly different between the groups with elevated (>3 mmol/l) and normal serum D-lactate concentrations. This study shows that hyper-D-lactataemia occurs frequently in diarrhoeic calves, has no impact on prognosis but may contribute to the clinical picture associated with metabolic acidosis in these animals.     

Determinants and Utility of the Anion Gap in Predicting Hyperlactatemia in Cattle

The objectives of this study were to investigate the determinants of the anion gap (AG) in cattle and to evaluate the utility of AG in detecting hyperlactatemia in sick neonatal calves and adult cattle. The AG was calculated as AG = ([Na+] + [K+]) - ([Cl^-] + [HCO₃]), with all values in mEq/L. The AG of healthy neonatal calves (n = 16) was 29.6 ± 6.2 mEq/L (mean ± SD), and the blood L-lactate concentration ranged from 0.5 to 1.2 mM/L. The AG was significantly (P > .05) correlated with serum phosphate (r = .66) and creatinine (r = .51) concentrations. The AG of neonatal calves with experimentally induced diarrhea (n = 16) was 28.6 ± 5.6 mEq/L, and the blood L-lactate concentration ranged from 1.1 to 2.9 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .67), serum phosphate concentration (r = .63), creatinine concentration (r = .76), and blood pH (r = -.61). The AG of adult cattle with abomasal volvulus (n = 41) was 20.5 ± 7.8 mEq/L, and the blood L-lactate concentration ranged from 0.6 to 15.6 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .60), serum phosphate concentration (r = .71), creatinine concentration (r = .65), albumin concentration (r = .47), total protein concentration (r = .54), blood pyruvate concentration (r = .67), and blood pH (r = -.41) but not plasma β-OH butyrate concentration. The results indicate that the AG in cattle is only moderately correlated with blood L-lactate concentration and is similarly correlated with serum phosphate and creatinine concentrations in neonatal calves and adult cattle, as well as with serum albumin and total protein concentrations in adult cattle. Anion gap determination is of limited usefulness in predicting blood L-lactate concentration in sick cattle, whereas the correlation between AG and serum creatinine concentration in sick cattle suggests that an increased AG should alert the clinician to the potential presence of uremic anions.     

Determination of lactose and xylose malabsorption in preruminant diarrheic calves.

In preliminary studies feeding the poorly absorbed carbohydrate sorbitol at 2.3 g/kg body weight as an indication of maximal fermentative capacity failed to produce the expected large increase in breath hydrogen excretion but did produce a transient diarrhea in five out of six control calves. Twelve healthy control and eighteen diarrheic calves were fed lactose or D-xylose on consecutive days at 1.15 g/kg body weight and a concentration of 46 g/L. Breath and blood samples were collected at 1 h intervals from 0 to 7 h. After administration of lactose, there was a significant increase in breath hydrogen excretion in diarrheic versus control calves. The increase in plasma glucose concentrations was delayed in diarrheic calves but the area under the absorption curve was similar in control and diarrheic calves. After administration of D-xylose, breath hydrogen excretion did not increase significantly but plasma D-xylose concentrations were significantly reduced in diarrheic calves. The pathogens commonly isolated from the feces were Cryptosporidium species, rotavirus and coronavirus. The number of pathogens and the severity of the calves' acid-base deficit were not related to the severity of carbohydrate malabsorption. Decreased absorption of lactose and D-xylose may be the result of intestinal villous atrophy caused by viral or parasite infection. It was concluded that carbohydrate malabsorption rather than a specific lactose maldigestion is a significant problem in diarrheic calves. Diarrheic calves appear to digest and absorb lactose when fed in small amounts.     

The prevalence and clinical relevance of hyperkalaemia in calves with neonatal diarrhoea

One hundred and twenty-four calves with neonatal diarrhoea were investigated in order to assess the prevalence of hyperkalaemia and the associated clinical signs. Hyperkalaemia (potassium concentration >5.8 mmol/L) was recognized in 42 (34%) calves and was more closely associated with dehydration than with decreases in base excess or venous blood pH. In 75 calves with normal blood concentrations of D-lactate (i.e. ?3.96 mmol/L), K concentrations were moderately correlated with base excess values (r = ?0.48, P < 0.001). In contrast, no significant correlation was observed in 49 calves with elevated D-lactate. Only three hyperkalaemic calves had bradycardia and a weak positive correlation was found between heart rate and K concentrations (r = 0.22, P = 0.014). Ten of the 124 calves had cardiac arrhythmia and of these seven had hyperkalaemia indicating that cardiac arrhythmia had a low sensitivity (17%) but a high specificity (96%) as a predictor of hyperkalaemia.In a subset of 34 calves with base excess values ??5 mmol/L and D-lactate concentrations <5 mmol/L (of which 22 had hyperkalaemia), changes in posture/ability to stand could be mainly explained by elevations of K concentrations (P < 0.001) and to a lesser extent by increases in L-lactate concentrations (P = 0.024). Skeletal muscle weakness due to hyperkalaemia alongside hypovolaemia may produce a clinical picture that is similar to that in calves with marked D-lactic acidosis. However, since reductions in the strength of the palpebral reflex are closely correlated with D-lactate concentrations, a prompt palpebral reflex can assist the clinical prediction of hyperkalaemia in calves presenting with a distinct impairment in their ability to stand (specificity 99%, sensitivity 29%).     

Effect of glutamine or glycine containing oral electrolyte solutions on mucosal morphology, clinical and biochemical findings, in calves with viral induced diarrhea.

Twenty-one diarrheic calves were randomly assigned to 1 of 3 oral electrolyte treatments. The treatments were either a conventional oral electrolyte containing glycine (40 mmol/L) as the amino acid, an oral electrolyte in which glutamine (40 mmol/L) replaced glycine or an electrolyte in which high concentrations of glutamine (400 mmol/L) replaced glycine. The calves were monitored while on trial and at the end of the treatment they were euthanized and a necropsy was immediately performed. Calves fed the high glutamine electrolyte had more treatment failures (2/7 versus 0/7 for each of the other 2 treatments). There was a significant effect of type of electrolyte on fecal consistency. Calves fed the glycine containing electrolyte had the most solid feces. Duodenal villus height was significantly affected by the type of electrolyte: values (mean +/- 1 SEM) were 0.61 +/- 0.09, 0.46 +/- 0.05, and 0.59 +/- 0.07 mm for high glutamine, low glutamine and glycine electrolytes respectively. There was no significant difference in small intestinal surface area between groups. High glutamine treated calves had the greatest capacity to absorb xylose from the small intestine but this difference was not statistically significant. Overall, this trial does not suggest that substituting glutamine for glycine in oral electrolyte solutions improves treatment of diarrheic calves or speeds mucosal healing.     

Investigations on the influence of serum D-lactate levels on clinical signs in calves with metabolic acidosis

Correlations between the degree of acidosis and clinical signs (changes in posture, behaviour, intensity of suckling reflex) in neonatal diarrhoeic calves have been described in various studies. However, base excess values varied widely in calves exhibiting similar clinical symptoms. The objective of this study was to elucidate whether the clinical picture of acidotic calves with neonatal diarrhoea is influenced more by D-lactate concentration than by degree of acidosis. Eighty calves up to three weeks old that were admitted to the II Medical Animal Clinic with acute diarrhoea and base excess values between -10 and -25 mmol/L were included in the prospective study. Posture, behaviour, suckling and palpebral reflexes, and position of the eyeballs were scored during the initial examination. Base excess and serum D-lactate and urea concentrations were determined in venous blood. In order to quantify the influences of base excess and d-lactate on the clinical parameters, groups of different clinical categories were compared. The results show that variations in behaviour, and in posture can be better explained by elevations of serum D-lactate concentrations than by decreases in base excess. Disturbances of the palpebral reflex appear to be almost completely caused by high levels of D-lactate.     

Fecal D- and L- lactate, succinate, and volatile fatty acid levels in young dairy calves

For evaluation of physiologically significant organic anions in the colonic environment, 87 samples of normal feces were collected from the rectum of 15 calves less than 60 days old. The calves were fed milk replacer with free access to starter diet and hay. After fecal extraction with water, pH, D- and L-lactate, succinate, and volatile fatty acid (VFA) concentrations were determined. There was wide variation in fecal pH (4.3 to 7.7). Higher lactate concentrations were observed in feces samples with lower pH, and most of these samples were collected during the first 4 weeks of life. Elevated lactate concentrations included both the D- and L-isomers, and the D-isomer comprised approximately 30-50% of total lactate. Elevated succinate concentrations were observed in only 8 fecal samples, while other samples had lower or trace amounts of succinate. Elevated fecal succinate showed no relationship with fecal pH or VFA concentrations. Fecal VFA concentrations were lower in samples collected in the early postnatal stage, but fecal VFA concentrations were not necessarily related to age. We confirmed that fecal D- and L-lactate concentrations increased with a concomitant decrease of VFA in the acidic lumen of the colon, although acidic feces were not necessarily accompanied by elevated concentrations of lactate. In contrast, succinate production was not related to fecal pH or VFA concentrations.     

Investigations on the association of D-lactate blood concentrations with the outcome of therapy of acidosis, and with posture and demeanour in young calves with diarrhoea

The objective of this prospective study was to elucidate whether amounts of bicarbonate needed for correction of acidosis and normalization of clinical signs are influenced by blood D-lactate concentrations in calves with diarrhoea. In 73 calves up to 3 weeks old with acute diarrhoea and base excess values below -10 mmol/l correction of acidosis was carried out within 3.5-h by intravenous administration of an amount of sodium bicarbonate which was calculated using the formula: HCO (mmol) = body mass (kg) x base deficit (mmol/l) x 0.6 (l/kg). Clinical signs, venous base excess, and plasma D-lactate concentrations were monitored immediately following admission, following correction of acidosis at 4 h and 24 h after admission. The base excess and plasma D-lactate concentrations throughout the study were -17.8 +/- 4.0, -0.4 +/- 0.4, -3.0 +/- 5.5 mmol/l (base excess), and 10.0 +/- 4.9, 9.8 +/- 4.8, 5.4 +/- 3.4 mmol/l (D-lactate) for the three times of examination. Metabolic acidosis was not corrected in more than half of the calves (n = 43) by the calculated amount of bicarbonate, whereas the risk of failure to correct acidosis increases with D-lactate concentrations. The study shows that calves with elevated D-lactate concentrations do not need additional specific therapy, as D-lactate concentrations regularly fall following correction of acidosis and restitution of body fluid volume, for reasons that remain unclear. However, calves with distinct changes in posture and demeanour need higher doses of bicarbonate than calculated with the factor of 0.6 in the formula mentioned above probably because of D-hyperlactataemia.     

Evaluation of the Total Carbon Dioxide Apparatus and pH Meter for the Determination of Acid-Base Status in Diarrheic and Healthy Calves

Three simple tests of acid-base status were evaluated for field use. Blood samples were collected from 20 diarrheic and 24 healthy calves less than six weeks of age. One sample was collected anaerobically and immediately analyzed on a blood gas analyzer. The other samples were used for measurement of blood and serum pH using a pH meter and pH paper, and for serum total carbon dioxide (TCO₂) using a TCO₂ apparatus. The TCO₂ apparatus gave the best results and would be useful in the field. TCO₂ apparatus measurements had a high correlation, r=0.91, with blood gas analyzer blood bicarbonate values. Healthy calves have a serum TCO₂ content of 30 mmol/L and bicarbonate requirements for correcting metabolic acidosis in diarrheic calves can be calculated:

Bicarbonate required (mmol) = (30-TCO₂) × Body Weight × 0.6 This can be converted to grams of sodium bicarbonate by dividing by 12.

     

Net portal absorption of lactate and volatile fatty acids in steers experiencing glucose-induced acidosis or fed a 70% concentrate diet ad libitum

Five crossbred steers (347 kg) were surgically fitted with rumen fistulae, hepatic portal, abdominal aorta and mesenteric catheters to measure organic acid absorption from the gut during acute [intraruminal glucose, 12 g/kg body weight (G)] or subacute [ad libitum 70% concentrate diet (C)] acidosis. Samples were taken at time 0, then every 2 h for 48 h after a switch from an alfalfa diet to C, or dosing with G. Steers receiving C received G 1 wk later so that five steers provided four observations/treatment. Blood flow rates were determined by infusion of para-amino hippuric acid (PAH) and averaged 767.8 and 712.5 liters/h for C and G, respectively. Animals consuming C averaged 13.6 kg dry matter from 0 to 24 h and 1.5 kg from 24 to 48 h. Rumen pH declined to 4.2 for G compared with 6.0 for C. Blood pH and HCO3 showed only slight depressions for G from 16 to 26 h, the period of lowest rumen pH. Rumen L-lactate concentration averaged 53.4 mM (peak 77 mM) and 2.1 mM for G and C, respectively. Rumen D-lactate concentration averaged 30.2 mM (peak 47 mM) for G and 1.2 mM for C. Net portal absorption of L-lactate averaged 96.6 and 164.4 mmol/h, whereas that of D-lactate averaged 10.5 and 71.8 mmol/h for C and G, respectively. Mean net portal volatile fatty acid absorptions were 442.8, 192.1, 53.8, 5.3 and 10.4 mmol/h (C) and 100.0, 47.2, 9.4, .98 and .78 mmol/h (G) for acetate, propionate, butyrate, isobutyrate and isovalerate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of eae+ Escherichia coli isolated from healthy and diarrheic calves.

Strains of Escherichia coli from 101 healthy and 114 diarrheic calves were screened by PCR for the eae (intimin) gene and Shiga toxin genes (stx). Each eae+ and eae/stx+ strain was examined for antimicrobial susceptibility, enterohemolysin activity, and the somatic O antigen was determined. An immunoassay was used to detect Shiga toxin antigens for the eae/stx+ E. coli. Significantly more (p = 0.005) of the healthy calves carried eae+ and eae/stx+ E. coli in their feces when compared to strains from diarrheic calves. Moreover, Shiga toxin antigens were detected significantly more (p = 0.001) often among the eae/stx+ strains from healthy calves when compared to eae/stx+ strains from diarrheic calves. However, significantly more (p = 0.001) of the eae+ and eae/stx+ strains from diarrheic calves were resistant to at least one of the antimicrobials tested, and the strains from diarrheic calves had a significantly (p = 0.05) higher rate of antimicrobial resistance to at least two different antimicrobial classes. No significant difference (p> or =0.05) was detected among the eae+ and eae/stx+ strains from healthy and diarrheic calves for enterohemolysin production. Serogroups O-negative, O5, O26, and O111 were predominate among both healthy and diarrheic calves.     

Ultrasonographic imaging of abomasal milk clotting and abomasal diameter in healthy and diarrheic calves

In case of diarrhea calves are treated with oral rehydration solutions (ORS), which are known to increase abomasal pH and inhibit milk clotting in vitro. Nevertheless, recent studies have shown that ORS with HCO₃^‐ ≤ 62 mmol/L do not interfere with abomasal milk clotting in healthy calves. However, in diarrheic calves, feeding ORS and milk simultaneously may disturb abomasal curd formation and exacerbate diarrhea due to faster abomasal passage of ingesta. Therefore, the aim of the present study was to ultrasonographically examine abomasal milk clotting and diameter after feeding milk and milk replacer (MR) with and without ORS to healthy and diarrheic calves. Abomasal curd formation and diameter in healthy and diarrheic calves were ultrasonographically imaged before and after feeding milk, MR and ORS prepared in milk or MR. Feeding mixtures of milk or MR with ORS did not cause any remarkable differences in the ultrasonographic images of abomasal content. Moreover, abomasal milk clotting was not disturbed due to diarrhea. Statistically significant differences of abomasal diameter after feeding between healthy and diarrheic calves indicated that abomasal emptying is delayed in diarrheic calves. Hence, further studies are needed to determine reasons for decelerated abomasal passage in calves suffering from diarrhea.     

Comparison of ventral coccygeal arterial and jugular venous blood samples for pH, pCO2, HCO3, Be(ecf) and ctCO2 values in calves with pulmonary diseases

The aim of this study was to determine whether venous blood samples can be used as an alternative to arterial samples in calves with respiratory problems and healthy calves. Jugular vein and ventral coccygeal artery were used to compare blood gas values. Sampling of the jugular vein followed soon after sampling of the ventral coccygeal artery in healthy calves (group I) and calves with respiratory problems (group II). Mean values of arterial blood for pH, pCO2, HCO3act in healthy calves were 7.475 +/- 0.004, 4.84 +/- 0.2 kPa, 28.45 +/- 1.30 mmol/L compared with venous samples, 7.442 +/- 0.006, 6 +/- 0.3 kPa, 30.93 +/- 1.36 mmol/L, respectively. In group II, these parameters were 7.414 +/- 0.01, 5.93 +/- 0.3, 27.73 +/- 1.96 mmol/L for arterial blood and 7.398 +/- 0.008, 6.85 +/- 0.2 kPa, 29.77 +/- 1.91 mmol/L for venous blood, respectively. There were no statistically significant differences between arterial and venous pH, HCO3act, Be(ecf), ctCO2 values with the exception of pCO2 (P = 0.001) in group II. In group I, correlation (r2) between arterial and venous blood pH, pCO2, HCO3act were 84.5%, 87.5%, 95.7%, respectively compared with the same parameters in group II, 80.8%, 77.1%, 70.3%. In conclusion, venous blood gas values can predict arterial blood gas values of pH, pCO2 and HCO3ecf, Be(ecf) and ctCO2- for healthy calves but only pH values in calves with acute respiratory problems (r2 value>80%).     

Studies on Diarrhea in Neonatal Calves: The Plasma Proteins of Normal and Diarrheic Calves During the First Ten Days of Age

The concentration of serum proteins and plasma fibrinogen were determined in 151 normal and 49 diarrheic calves at intervals from birth to ten days of age. There were significant differences in the concentrations of the various serum proteins in normal calves when the results were analysed at six age intervals. There was no significant relationship between the concentration of the various proteins and the season of the year.

Of the diarrheic calves, those that died had significantly lower gamma globulin concentrations than the other calves. Severely diarrheic and dehydrated calves had significantly increased serum albumin and alpha glabulin concentrations and decreased gamma globulin concentrations. No significant variation occurred in total serum protein concentration. Plasma fibrinogen concentrations were similar in normal and diarrheic calves.

     

A comparison of pH determination methods in food animal practice

The accuracy of a portable pH meter in measuring blood pH in neonatal calves, urine pH, and ruminal fluid pH in cows has been assessed. Thirty-five diarrheic and 15 healthy beef calves were used for blood gas analysis; 57 healthy dairy cows provided voided urine samples; and ruminal fluid samples were obtained from 10 dairy cows with ruminal fistulas on 4 separate days. Measurements of blood pH were obtained from an automated blood gas analyzer and the portable pH meter. Measurements of urine and ruminal fluid pH were determined with the benchtop pH meter, urinalysis strips, narrow range pH paper, and the portable pH meter. The portable pH meter was more accurate in measuring urine pH and ruminal fluid pH in cows than blood pH in neonatal calves. The urinalysis strips and the narrow range pH paper were found adequate to evaluate urine and ruminal pH.     

Pharmacokinetics and metabolic inertness of doxycycline in calves with mature or immature rumen function

The pharmacokinetic determinants of doxycycline were calculated after a single IV administration of the drug (20 mg/kg of body weight) in 5 Angus calves with mature rumen function and 4 Holstein calves with immature rumen function. Doxycycline disposition was best described by means of an open 2-compartment model. Median elimination half-life was 14.17 hours (Angus) and 9.84 hours (Holstein). Mean (+/- SEM) total body clearance was 1.07 (+/- 0.06) and 2.20 (+/- 0.21) ml/min/kg in Angus and Holstein calves, respectively. Mean extent of doxycycline binding to serum proteins was 92.3% (+/- 0.8%). The large steady-state volume of distribution (1.31 +/- 0.11 L/kg in Angus and 1.81 +/- 0.24 L/kg in Holstein calves), despite the small free fraction in serum, suggested a relatively unrestricted access of drug into the intracellular compartment and/or appreciable tissue binding. Results of mass spectrometric analysis of serum and urine from calves administered doxycycline IV revealed absence of biotransformation, because only parent drug could be detected. Thus, doxycycline may be a valuable antibiotic for use in food animals pending further studies on tissue residues, safety, and efficacy.     

Effect of dietary lactic acid on rumen lactate metabolism and blood acid-base status of lambs switched from low to high concentrate diets.

Two experiments were conducted with ruminally fistulated wether lambs to determine the effect of lactic acid addition to a hay diet on rumen lactate metabolism, blood acid-base status and subsequent adaptation to a high concentrate diet. In Exp. 1, lambs were fed mature brome hay (H), H plus 5% (w/w) D,L lactic acid (H5L) or H plus 10% lactic acid (H10L) (three lambs per treatment) for 14 days (phase I) then switched to a 90% concentrate diet for 2 days (phase II). In Exp. 2, lambs were fed alfalfa-brome hay (H) (six lambs), H plus 2.5% lactic acid (H2.5L) (six lambs) or H plus 5% lactic acid (H5L) (four lambs) during phase I, then switched to a 70% concentrate diet (3 days) followed by a 90% concentrate diet (10 days) (phase II). During both experiments rumen fluid samples were taken periodically for pH and lactate analyses and in vitro L- or D-lactate disappearance (IVLD) studies. Blood samples were taken to measure acid-base status, serum lactate, and serum calcium, magnesium and phosphorus. Dietary lactic acid enhanced IVLD during phase I of both experiments. L and D isomer IVLD rates were similar and followed zero-order kinetics. In Exp. 2, IVLD increased rapidly during phase II in response to increased concentrate level in the diet; the enhanced rates of H2.5L and H5L lambs were sustained for the first 3 days of phase II. Blood data from both experiments indicated a deleterious effect of dietary lactic acid on blood acid-base balance; however, this treatment effect was not manifested in any symptoms of acute acidosis. There was a decrease (P less than .05) in serum calcium during phase II of both experiments. In Experiment 1, serum calcium increased linearly (P less than .05) in response to dietary lactic acid level. In Exp. 1, rumen fluid total lactate and L-lactate were lower (P less than .05) for H5L vs H lambs during phase II. However, all lambs in Exp. 1 experienced acute acidosis; four of the nine lambs subsequently died. There was evidence of acidosis in Exp. 2, but there were no clear treatment effects during phase II on rumen fluid pH or lactate, or feed intake. All lambs adapted to the high concentrate diets as evidenced by rumen lactate levels and feed intakes. In both experiments, the proportion of L-lactate in rumen fluid decreased from almost 100 to about 50% of total lactate by the end of phase II.