Healthy Neonatal Calves Research Articles

Effects of doxapram, prethcamide and lobeline on spirometric, blood gas and acid–base variables in healthy new-born calves

A number of drugs have been used to treat asphyxia in new-born calves and the aim of the current study was to investigate the effect of commonly-used stimulant drugs on ventilation, arterial blood gas and acid base variables. A group (n=18) of new-born (3-15 h old) calves were treated in a randomised sequence with doxapram (40 mg, IV), lobeline (5mg, IV) or prethcamide (5 mL, consisting of 375 mg crotethamide and 375 mg cropropamide, buccally). Blood and spirometric measurements, using an ultrasonic spirometer, were collected prior to and 1, 5, 15, 30, 60, 90 min after administration of each drug. Doxapram caused a significant increase in the respiratory rate, peak inspiratory and expiratory flow and minute volume (V(min)) during the 90-min post-treatment study period, although maximum values occurred 1 min after treatment. The V(min) increased from 13.8 ± 5.0 L to 28.5 ± 12.3 L. Prethcamide, but not lobeline, also caused significant increases in inspiratory and expiratory volumes. The effects of doxapram on ventilation were accompanied by an increase in arterial partial pressure of oxygen (P(a)O(2)) (77.7 ± 18.8 mm Hg to 93.2 ± 23.7 mm Hg), a decrease in arterial partial pressure of carbon dioxide (P(a)CO(2)) (42.6 ± 4.9 mm Hg to 33.1 ± 6.6mm Hg), a significant increase in pH and a decrease in bicarbonate concentration and base excess 1 min after treatment. Prethcamide caused a gradual increase in P(a)O(2) and decrease in P(a)CO(2) over 90 min, whereas lobeline had no measurable effect on the investigated variables. Of the three treatments, only doxapram had a distinct stimulatory effect on respiration in healthy neonatal calves and may therefore be useful in the treatment of calf asphyxia.

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

Fetal/neonatal alloimmune thrombocytopenia is a frequent disease in humans where alloantibodies against platelet Ags lead to platelet destruction and hemorrhage. Although a role in the disease for Abs against MHC has been suspected, this has not been formally demonstrated. Since 2007, a hemorrhagic syndrome due to thrombocytopenia and designated as bovine neonatal pancytopenia (BNP) has been recognized in calves in several European countries. An inactivated antiviral vaccine is strongly suspected to be involved in this syndrome because of its highly frequent use in the dams of affected calves. In this study, we show that BNP is an alloimmune disease, as we reproduced the signs by transferring serum Abs from vaccinated BNP dams into healthy neonatal calves. Ab specificity was strongly associated with the presence of allogeneic MHC class I Abs in the dams. MHC class I staining was also observed on Madin-Darby bovine kidney cells, a cell line related to the one used to produce the vaccine Ag. Our report emphatically demonstrates that alloimmunization against MHC class I is associated with a substantial risk of developing cytopenia-associated syndromes in neonates when a cell line of the same species is used to produce an inactivated vaccine injected into the mother.

Plasma potassium-lowering effect of oral glucose, sodium bicarbonate, and the combination thereof in healthy neonatal dairy calves

Hyperkalemia is a common complication in neonatal diarrheic dairy calves and is corrected by administration of glucose or sodium bicarbonate. Although the hypokalemic effect of glucose is well established in other species, controversial results are reported for sodium bicarbonate. Our objective was to study the effect and mechanism of action of glucose and sodium bicarbonate on the potassium homeostasis of healthy neonatal dairy calves. Nine healthy neonatal Holstein-Friesian calves underwent 3 oral treatments with 2L of NaHCO3 (150mmol/L), glucose (300mmol/L), and glucose+NaHCO3 solution (300mmol/L+150mmol/L) in randomized order. Blood was obtained before treatment (T0) and at 30-min intervals thereafter. Changes between each time point and T0 were determined for all parameters. Urine was collected volumetrically to determine total renal potassium excretion over an 8-h posttreatment period. Plasma volume changes were extrapolated from changes in plasma protein concentration. Treatment and time effects were tested with repeated-measures ANOVA. Multivariate stepwise regression analysis using dummy variable coding was conducted to identify associations between changes in plasma potassium concentration ([K]) and changes in plasma glucose concentration ([glucose]), blood base excess, and plasma volume. Oral glucose and sodium bicarbonate treatments decreased [K] by 25 and 19%, respectively, whereas the combination of both compounds caused an intermediate [K] decline (22%). For the glucose treatment, the decline in [K] was only associated with changes in plasma [glucose] (partial R2=0.19). In NaHCO3-treated calves, [K] decline was associated with change of extracellular volume (partial R2=0.31) and blood base excess (partial R2=0.19). When glucose and NaHCO3 were combined, [K] decline was associated with changes in plasma volume (partial R2=0.30), BE (R2=0.22), and [glucose] (partial R2=0.03). Our results indicate that glucose lowers plasma [K] mainly through an insulin-dependent intracellular translocation of K, whereas NaHCO3 causes hypokalemia through hemodilution followed by intracellular translocation of K caused by the strong ion effect. The combination of glucose and NaHCO3 at the dosage used in this study does not have an additive hypokalemic effect. When combined, hemodilution and strong ion effect have the strongest effect on plasma [K], whereas the insulin-dependent effect of glucose appears to be blunted.

Natural <i>in utero</i> infection of neonatal calves with bovine viral diarrhoea virus on a large dairy farm in Saudi Arabia

The dairy industry is a large and important business in Saudi Arabia. Although farms are administered to high international standards, some reproduction problems, of uncertain aetiology, are encountered. The most frequently seen are conception failures, abortions, stillbirths and the birth of weak or malformed calves. These conditions are suggestive of bovine viral diarrhoea virus (BVDV) infection. Unfortunately, very little published information is available regarding the impact of this disease on cattle populations in Saudi Arabia. As a consequence, the present study was carried out and is the first of its kind in Saudi Arabia and the Gulf region. The aim of the study was to elucidate the role of in utero BVDV infection leading to the birth of weak or malformed calves on a large dairy farm in Saudi Arabia. The study was divided into two parts. Firstly, apparently healthy neonatal calves were sampled for the detection of pre-colostral serum antibodies to BVDV. The presence of these antibodies indicates exposure of the foetus to BVDV during the last two trimesters of gestation. Secondly, tissue samples from malformed neonatal calves were examined for the presence of BVDV antigens. Detection of such antigens confirms exposure of the foetus to the virus during the first trimester of gestation. The results of the investigation indicated that 36.1% of the neonatal calves were exposed to BVDV infection in utero. This is higher than what has been reported in the literature and suggests that dairy farmers in the Arabian Peninsula need to be made aware of the dangers of BVDV infections in their herds. The epidemiological significance of the results is discussed.

Isolation of pathogenic aerobic bacteria from the blood of septicaemic neonatal calves and the susceptibility of isolates to various antibiotics

An automated blood culture system (BACTEC 9240) was used for the isolation of aerobic bacteria from the blood of septicaemic neonatal calves. Blood samples were collected from 90 clinically septicaemic and 20 healthy neonatal calves and inoculated into blood culture bottles. There were 89 significant isolates from 90 positive blood cultures using the BACTEC system. Escherichia coli was the most common pathogen detected accounting for 56 (63%) out of 89 isolates. The other pathogens were beta-haemolytic streptococci (15.7%), Staphylococcus aureus (10.1%), Klebsiella sp. (5.6%) and Corynebacterium sp. (5.6%). All isolates showed a susceptibility rate of 100% to enrofloxacin, cefepim, cefoperazone/sulbactam, imipenem and meropenem while some of them were ranged from 75 to 91.7% susceptible to amoxicillin/clavulanic acid, ampicillin/sulbactam, gentamicin and cephalosporins.

Neonatal immune response of Brazilian beef cattle to vaccination with Clostridium botulinum toxoids types C and D by indirect ELISA

Types C and D strains of Clostridium botulinum are commonly related to avian and mammalian botulism. Although there are numerous vaccine recommendations, little research has been conducted to indicate the real effectiveness of vaccine timing or the ideal immunization protocol for young beef calves. Four commercially available vaccines, two bivalent (Clostridium botulinum types C and D; vaccines 1 and 2) and two polyvalent (all Clostridium spp. including Clostridium botulinum types C and D; vaccines 3 and 4), that are currently used in Brazilian herds, were tested in order to verify the maternal immune response. One hundred cows, divided into four vaccinated groups and one unvaccinated group, were given a two-dose subcutaneous immunization, at day zero, followed by a second dose given at 42 days post-vaccination, which corresponded to 40 days before birth. Serum samples (n = 75) were collected only from healthy neonatal calves at 0, 7, 45 and 90 days post-calving (DPC) and subjected to indirect ELISA using the purified C and D holotoxins as capture antigens. The serological profile showed that all vaccines were able to induce a satisfactory neonatal immune response to both holotoxins at 7 DPC. However, at 45 and 90 DPC, a significant reduction (p < 0.05) was observed in the antibody level against C and D holotoxins in all tested vaccines. Neonatal immunization in calves is compromised by significant levels of maternal antibodies so that the necessity of planning a calf vaccination program involves assessment of disease risks at the production site. Finally, our findings represent the first demonstration of maternal immunity transferred to neonatal beef calves, including immunity levels after vaccination against Clostridium botulinum toxoids C and D.

Respiratory and cardiovascular effects of doxapram and theophylline for the treatment of asphyxia in neonatal calves

Respiratory stimulants are widely used in asphyxic neonatal calves despite a lack of data about their effectiveness and indications of possible side effects. The effect of doxapram and theophylline on respiratory, cardiovascular, and acid-base variables was investigated in 10 healthy neonatal calves (Bos Taurus). A venous, a peripheral arterial, and a pulmonary arterial catheter were placed, and central venous, pulmonary, and systemic blood pressures and cardiac output were measured using thermodilution technique. Doxapram, but not theophylline, led to an immediate increase in respiratory rate (P ≤ 0.01). The arterial pCO 2 decreased to 27.1 ± 4.7 mm Hg within 30 sec after doxapram administration and to 46.3 ± 5.8 mm Hg within 120 min after theophylline administration (P < 0.0001). The systolic pulmonary pressure increased from 70 ± 8 mm Hg (mean ± SD) to 93 ± 19 mm Hg within 30 sec after doxapram, but decreased after theophylline. The pulmonary vascular resistance also increased after doxapram and decreased after theophylline (P < 0.01). Doxapram had a more pronounced and faster effect on respiratory rate and elimination of CO 2 than theophylline. Doxapram, but not theophylline, is indicated for treatment of postnatal asphyxia in calves, but there are potential cardiovascular side effects.

Nutrient uptake by viscera drained by the portal vein in neonatal calves during intravenous infusion of glutamine

Abstract Objective To quantify glutamine use by viscera drained by the portal vein in neonatal calves and to determine whether uptake could be stimulated by long-term IV infusion or long-term use of oral supplements. Animals 4 healthy neonatal calves. Procedure A femoral artery, jugular vein, and the portal vein were surgically cannulated in each calf. Blood flow in the portal vein was measured, using an ultrasonic transit-time flow probe. Calves were given an IV infusion of glutamine on days 6, 8, and 10 after surgery. Before the first infusion, calves were fed a diet of milk only. The diet was supplemented with glutamine for the second and third infusions. Glutamine was administered via the jugular vein during a 5-hour period. Venous and arterial blood samples were collected every hour for 5 hours. Results During glutamine infusion, uptake of glutamine by viscera drained by the portal vein increased in association with increased production of ammonia. Glutamine supplementation of the diet did not alter glutamine uptake. Glutamine infusion did not increase viscera uptake of indispensable amino acids. Longterm use of glutamine supplements or infusion of glutamine for periods of more than 1 hour increased glutamine uptake by viscera. Arterial leucine concentration and uptake of leucine by the viscera decreased during glutamine infusion, indicating that leucine became the limiting factor. Conclusion Glutamine administration (supplements or infusions) to calves may require that a mixture of amino acids be provided to improve effectiveness. Clinical Relevance Glutamine may be beneficial in treatments designed to promote intestinal healing in diarrheic calves. (Am J Vet Res 1999;60:446-451)

Examination of metabolism of viscera drained by the portal vein in neonatal calves, using short-term intravenous infusions of glutamine and other nutrients

Abstract Objective To quantify glutamine use in viscera drained by the portal vein in neonatal calves and to assess the relative nutritional importance of glutamine, glucose, and acetate for enterocytes. Animals 5 healthy neonatal calves. Procedure A femoral artery, jugular vein, and the portal vein were surgically cannulated in each calf. Blood flow in the portal vein was measured by use of an ultrasonographic transit-time flow probe. A series of solutions was infused on 4 days for each calf. On the infusion days, acetate, glucose, glutamine, and saline (0.9% NaCl; control) solutions were administered IV during 1-hour periods via the jugular vein. Venous and arterial blood samples were collected during the last 15 minutes of each 1-hour infusion. Results Uptake of glutamine and glucose by viscera drained by the portal vein was 0.3 ± 1.1 and 1.9 ± 3.1 µmol/kg0.75/min, respectively, during saline infusion. During acetate, glucose, and saline infusions, glucose was a greater source of energy for the intestines than was glutamine. However, during glutamine infusion, uptake of glutamine by viscera drained by the portal vein increased significantly (29.9 ± 11.2 µmol/kg0.75/min), which was associated with an increase in ammonia production (7.0 ± 0.5 µmol/kg0.75/min). Toxicosis was not associated with IV administration of glutamine. Conclusion Glutamine infusion resulted in an increase in glutamine uptake by viscera drained by the portal vein, which was associated with an increase in ammonia production and a slight increase in oxygen consumption. Clinical Relevance These solutions may be used to develop treatments that enhance healing of intestines of diarrheic calves. (Am J Vet Res 1999;60:437-445)

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-] + [HCO-3]), 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 beta-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.

Effect of endotoxin on tirilazad mesylate (U74006F) pharmacokinetic parameters in neonatal calves.

The pharmacokinetics of the 21-aminosteroid tirilazad mesylate (U74006F) were studied in both healthy and endotoxin-challenged neonatal calves. Group I calves received a 3-h intravenous (i.v.) infusion of sterile saline (250 ml) and tirilazad mesylate (1.5 mg/kg i.v.) 1 h after the start of the saline infusion. Group II calves received tirilazad mesylate 1 h after the start of a 3-h endotoxin (3.25 micrograms/kg) infusion. The data obtained indicate that tirilazad mesylate follows a biexponential equation in neonatal calves. The area-derived volume of distribution (Vdarea) was 9.68 +/- 0.759 l/kg in healthy calves and 6.53 +/- 1.20 l/kg in endotoxin-challenged calves (P < 0.05). Similarly, significant (P < 0.05) decreases in steady-state volume of distribution (Vdss) and central volume (Vc) were observed in endotoxin-challenged calves (5.32 +/- 0.979 l/kg and 1.68 +/- 0.189 l/kg, respectively) compared to healthy calves (7.58 +/- 0.834 l/kg and 2.43 +/- 0.452 l/kg, respectively). A and B were significantly larger in endotoxin-challenged calves than in healthy calves (P < 0.05). Rate constants and their associated half-lives, area under the curve and clearance were not significantly altered by endotoxin challenge. Serum thromboxane generation (ex vivo) was evaluated as a marker of the drug's physiologic activity. There was no significant difference in thromboxane generation during clotting of blood from healthy and endotoxemic calves treated with tirilazad mesylate.

Bromodeoxyuridine labeling and DNA content of pulmonary arterial medial cells from hypoxia-exposed and nonexposed healthy calves

SUMMARY Vascular medial thickening is a prominent finding in people and animals with refractory neonatal pulmonary hypertension. Smooth muscle cells are capable of 2 distinct growth responses in vivo: hypertrophy or hyperplasia. Hypertrophic smooth muscle cells may undergo dna synthesis without cell division, leading to a polyploid state. To better understand the nature of smooth muscle cell growth in healthy and pulmonary hypertensive neonatal calves, we measured incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) and total dna content in medial cells from control (pulmonary arterial pressure = 32 ± 2 mm of Hg) and hypobaric hypoxia-exposed (pulmonary arterial pressure = 120 ± 7 mm of Hg) calves. Labeling of medial cells with BrdUrd measured by flow cytometry was increased (P &lt; 0.02) in pulmonary arteries of hypoxia-exposed calves (n = 5), compared with control calves (n = 5). Immunohistochemical localization of BrdUrd indicated that BrdUrd labeling of large elastic pulmonary arteries from hypoxia-exposed calves was increased almost exclusively in the outer half of the medial wall. Increased BrdUrd labeling of muscular pulmonary arteries from hypoxia exposed calves was observed in the arterial media and adventitia, and tended to exit in clusters. Analysis of dna content by flow cytometry indicated a decrease (P &lt; 0.05) in percentage of tetraploid medial cells in pulmonary arteries from hypoxia-exposed calves, compared with control calves. Bivariate analysis for BrdUrd labeling and dna content of cells from the pulmonary arteries of hypoxia-exposed calves indicated a subpopulation of diploid cells with positive BrdUrd labeling, suggestive of dna synthesis and subsequent cell division. Results are suggestive of smooth muscle cell hyperplasia in the vascular media of hypoxia-exposed calves.

Myoelectric activity of the small intestine in enterotoxin-induced diarrhea of calves

Summary Electrodes were surgically implanted at 15-cm intervals in the jejunum and ileum of 4 healthy neonatal calves so that myoelectric activity could be recorded on 2 consecutive days. On the first day, each calf received a control treatment, and myoelectric activity was recorded for 340 minutes. Phase I was recorded for a mean of 175.8 ± 22.8 minutes (51.5%), phase II for 124 ± 27.4 minutes (36.5%), and phase III for 40.3 ± 6 minutes (11.9%). On the second day, each calf was treated with approximately 200 μg of heat-stable enterotoxin (STa) of Escherichia coli orally. All calves developed diarrhea after the administration of STa. Phase I was recorded for a mean of 92.5 ± 42.3 minutes (27.2%), phase II for 227.3 ± 52.5 minutes (66.9%), and phase III for 20.3 ± 11.4 minutes (6.0%). Increase in phase II and decrease in phases I and III after STa administration were significant (P &lt; 0.05). Duration of the migrating myoelectric complex was longer after STa administration (median, 64 minutes), compared with the control treatment (median, 54 minutes). Minute rhythms, recorded on the day of toxin administration, ranged from 49 to 153 minutes. There was no difference between the number of migrating action potential complexes on the control days (range, 1 to 10), compared with those on treatment days (range, 1 to 14). These findings are suggestive that enterotoxin-induced diarrhea of calves is accompanied by increased total spiking activity and minute rhythms in the distal portion of the jejunum and ileum.