Evaluation Of An Additive Solution For Preservation Of Canine Red Blood Cells

The effect of an additive preservative solution on canine red blood cell posttransfusion viability (PTV) and on selected canine red blood cell biochemical parameters was studied. One unit (450 mL) of blood was collected from 6 clinically normal dogs into the anticoagulant citrate phosphate dextrose, centrifuged, and the plasma removed. The red blood cells were then suspended in 100 mL of a saline, adenine, dextrose, and mannitol solution and stored at 4°C. Aliquots were removed for study at 1, 10, 20, 30, 37, and 44 days. The 24-hour PTV of autologous red blood cells was determined using a sodium chromate (⁶¹Cr) label. Red blood cell concentrations of 2,3-diphosphoglycerate (2,3-DPG), adenosine-5'-triphosphate (ATP), and pH were also determined. Canine red blood cell PTV, pH, ATP, and 2,3-DPG concentrations decreased during storage ( P < .05). The PTV decreased from 94% using day 1 red blood cells to 80% and 75% using day 37 and day 44 red blood cells, respectively ( P < .05). Although the mean PTV of the day 44 stored units equaled the Food and Drug Administration (FDA) minimum standard for human red blood cells, the PTV was substandard in 75% of the day 44 units. The FDA standard was exceeded in 83% of the day 37 units. It was concluded that 37-day-old canine red blood cells preserved with a saline, adenine, dextrose, and mannitol solution are of acceptable quality for transfusion.     

Florfenicol in non-lactating dairy cows: pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils

Serial blood samples were collected and plasma concentrations of florfenicol (FLO) were measured following the administration of an intravenous bolus of 50 mg/kg FLO to five healthy non-lactating dairy cows. A triexponential equation provided the best fit of the data for four of the five cows. The mean value for beta corresponded to a half-life of 3.2 h. The mean apparent volume of distribution was 0.67 l/kg, and the mean body clearance was 0.15 l/kg/h. The extent of binding of FLO to bovine plasma proteins was determined in vitro at concentrations of 5 micrograms/ml and 50 micrograms/ml by equilibrium dialysis and ultrafiltration. The drug was 18% and 19% bound by equilibrium dialysis, and 23% and 19% bound by ultrafiltration, at 5 micrograms/ml and 50 micrograms/ml, respectively. Phagocytosis of 32phosphorus-labelled Staphylococcus aureus by bovine blood neutrophils was compared in vitro between neutrophils incubated in phosphate-buffered saline alone or in combination with 5, 125, or 1000 micrograms/ml chloramphenicol or FLO. There was no significant effect of chloramphenicol at any concentration. Florfenicol significantly inhibited phagocytosis at all concentrations, but the percentage inhibition was small. The clinical significance, if any, of this effect of FLO remains to be demonstrated.     

Effects of 5% and 10% Guaifenesin Infusion on Equine Vascular Endothelium

Twelve horses of various breeds and either sex were anesthetized with xylazine and ketamine injected into a median or lateral thoracic vein. During anesthesia, with the horse in sternal recumbency, a 14-gauge, 8.9 cm catheter was inserted into each jugular vein by using aseptic technique. Guaifenesin in water (100 mg/kg or a maximum dose of 50 grams) was infused into one jugular vein and an equal volume of 0.9% saline solution was infused into the other jugular vein. Seven horses received 10% guaifenesin, and five horses received 5% guaifenesin. The catheters were removed before the horses recovered from anesthesia. The horses were euthanatized approximately 48 hours later, and the jugular veins were removed for histologic examination. Adherent thrombus material was observed in all veins exposed to 10% guaifenesin and in one vein exposed to 5% guaifenesin. No evidence of thrombus was observed in four veins infused with 5% guaifenesin or in those infused with saline solution. These findings are of particular significance with horses at increased risk for thrombosis or thrombophlebitis.     

Influence of preinduction methoxamine, lactated Ringer solution, or hypertonic saline solution infusion or postinduction dobutamine infusion on anesthetic-induced hypotension in horses

A controlled study of the cardiovascular responses in horses anesthetized with acepromazine (0.05 mg/kg of body weight, IV), guaifenesin (100 mg/kg, IV), thiamylal (5.0 mg/kg, IV), and halothane in O2 (1.2 to 1.4% end-expired concentration) was performed to determine whether hypotension could be prevented by use of various treatments. Six horses were given 5 treatments in a randomized sequence: no treatment (control), methoxamine (0.04 mg/kg, IV), lactated Ringer solution (20.0 ml/kg, IV), 7.5% hypertonic saline solution (4.0 ml/kg, IV), or constant infusion of dobutamine (5.0 mg/kg/min, IV) during anesthesia. Heart rate, ECG, blood pressure, central venous pressure, cardiac output, blood gas analysis, PVC, and plasma total protein concentration were measured during the study. Compared with the control value, an increase in blood pressure during halothane administration was observed after administration of lactated Ringer solution, hypertonic saline solution, or dobutamine (P less than 0.05). The improved blood pressure response to hypertonic saline solution and dobutamine was related to an increase in cardiac output, which was statistically significant (P less than 0.05). Other statistically significant differences in cardiopulmonary responses among treatments were not observed during anesthesia. The PCV was increased in response to dobutamine infusion, and plasma total protein concentration was reduced in response to administration of hypertonic saline or lactated Ringer solution.     

Short-term compatibility of furosemide with crystalloid solutions

Parenteral veterinary furosemide is a 50-mg/mL solution with a pH of 8.0-9.3. The purpose of this study was to determine whether a commonly used veterinary formulation of 50 mg/mL of furosemide solution could be diluted in vitro without precipitation. Furosemide 50 mg/mL was diluted to concentrations of 10 and 5 mg/mL with 5% dextrose in water (D5W), 0.9% saline, lactated Ringer solution (LRS), and sterile water. Acidic sterile water and basic sterile water solutions were made by the addition of hydrochloric acid and sodium hydroxide, respectively, for use as controls to assess the effect of pH extremes for each concentration. After furosemide dilution, the final pH of each sample was measured, and samples were grossly and microscopically examined for clarity and crystal formation immediately and 1, 3, 5, and 8 hours after dilution. Gross precipitation and microscopic crystals were immediately observed in the acidic controls. Solutions of 5 mg/mL in LRS and 0.9% saline became slightly cloudy immediately, but no crystals were observed microscopically for 8 hours. Solutions of 10 mg/mL in D5W, 0.9% saline, LRS, and sterile water and solutions of 5 mg/mL in D5W and sterile water and the basic control were grossly clear, and no microscopic crystals were observed for 8 hours. On the basis of the results obtained in this in vitro investigation, this veterinary formulation of furosemide 50 mg/mL can be diluted without precipitation to a concentration of 10 mg/mL with D5W, 0.9% saline, LRS, or sterile water and to 5 mg/mL with D5W or sterile water and held for 8 hours.     

Optimum conditions for the turkey lymphocyte transformation test.

Optimum conditions for turkey lymphocyte transformation tests were determined. Thrice-washed turkey buffy-coat cells obtained after slow centrifugation (40 x g, 10 minutes) responded well to mitogenic stimulation. Turkey lymphocytes isolated on Ficoll-containing separation media largely lost their ability to respond to mitogens. Maximum responses were obtained with 2 x 10(7) lymphoid cells/ml. Responses to the mitogens were greatest when bovine fetal serum was used at a 2.5% concentration or pooled turkey serum and autologous plasma were used at a 1.25% concentration. Higher concentrations of turkey serum or plasma decreased the responses when sub-optimum doses of concanavalin-A (Con A) or phytohemagglutinin-P (PHA-P) were used. Serum-free cultures gave higher stimulation indices than cultures with serum only when sub-optimum doses of Con A or PHA-P were used. Optimum mitogen concentrations varied with individual birds, timing of the culture, temperature of incubation, and serum concentration in the cultures. Responses were usually greatest with final concentrations of 5 micrograms Con A/ml, 10 micrograms PHA-P/ml, and 20 micrograms pokeweed mitogen (PWM)/ml and when the cultures were incubated in 96-well microplates at 40 C in humidified air with 5% CO2 for 40-42 hours with pulsing with 3H-thymidine during the final 16 hours of incubation.     

Optimum conditions for the chicken lymphocyte transformation test.

Optimum conditions for chicken (Gallus gallus) lymphocyte transformation tests were determined. Thrice-washed chicken buffy-coat cells obtained after slow centrifugation (40 x g for 10 minutes) responded substantially better to mitogenic stimulation than lymphocytes isolated on separation media containing Ficoll. Maximum responses were obtained with 2 x 10(7) lymphoid cells/ml. Responses to the mitogens were greatest when fetal bovine serum was used at a 5% concentration or pooled chicken serum and autologous plasma were used at a 1.25% concentration. Optimum mitogen concentrations varied with individual birds, timing of the culture, temperature of incubation, and serum concentration in the cultures. When 1.25% chicken serum was used in the cultures, responses were usually greatest with final concentrations of 30-50 micrograms/ml of concanavalin A (Con A) and 30-50 micrograms/ml of phytohemagglutinin-P (PHA-P). The optimum concentration of pokeweed mitogen (PWM) varied from 1 to 40 micrograms/ml among the birds and was practically impossible to establish in general. The incubation in humidified air with 5% CO2 was significantly better at 40 C than at 37 C. The total culture time of 40 hours including pulsing with 3H-thymidine during the final 16 hours of incubation was the best for Con A- and PHA-P-stimulated cells, whereas a longer incubation of 64 hours gave the highest results with PWM stimulations.     

Globular resistance in bovine erythrocytes

An analysis of red blood cells resistance has been conducted by exposing red corpuscles of zebu, Baoule and metis zebu x Baoule, to different saline concentrations. The statistical results show no sex influence for all breeds. In zebu, there is a difference according to the type of hemoglobin concerned. The last ones differ also from these in taurine and metis. The data analysis were realised by calculating the mean of hemolysis percentages for all samples, as with NaCl concentrations in respect of a 50 per cent hemolysis. These differences can partly explain anaemia in bovine trypanosomiasis to Trypanosoma vivax or T. congolense, which less severely affects taurine Baoule than zebus.     

Effect of hypertonic vs isotonic saline solution on responses to sublethal Escherichia coli endotoxemia in horses

Cardiovascular responses to sublethal endotoxin infusion (Escherichia coli, 50 micrograms/ml in lactated Ringer solution at 100 ml/h until pulmonary arterial pressure increased by 10 mm of Hg) were measured 2 times in 5 standing horses. In a 2-period crossover experimental design, horses were either administered hypertonic (2,400 mosm/kg of body weight, IV) or isotonic (300 mosm/kg, IV) NaCl solution after endotoxin challenges. Each solution was administered at a dose of 5 ml/kg (infusion rate, 80 ml/min). Complete data sets (mean arterial, central venous, and pulmonary arterial pressures, pulmonary arterial blood temperature, cardiac output, total peripheral vascular resistance, heart rate, plasma osmolality, plasma concentration of Na, K, Cl, and total protein, blood lactate concentration, and PCV) were collected at 0 (baseline, before endotoxin infusion), 0.25, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after initiation of the endotoxin infusion. Blood constituents alone were measured at 0.5 hour and cardiovascular variables alone were evaluated at 0.75 hour. By 0.25 hour, endotoxin infusion was completed, a data set was collected, and saline infusion was initiated. By 0.75 hour, saline solutions had been completely administered. Mean (+/- SEM) cardiac output decreased (99.76 +/- 3.66 to 72.7 +/- 2.35 ml/min/kg) and total peripheral resistance (1.0 +/- 0.047 to 1.37 +/- 0.049 mm of Hg/ml/min/kg) and pulmonary arterial pressure (33.4 +/- 0.86 to 58.3 +/- 1.18 mm of Hg) increased for both trials by 0.25 hour after initiation of the endotoxin infusion and prior to fluid administration. For the remainder of the protocol, cardiac output was increased and total peripheral resistance was decreased during the hypertonic, compared with the isotonic, saline trial.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparative study of the effects of glycerol and hydroxyethyl starch in canine red blood cell cryopreservation

Hydroxyethyl starch (HES) is a nonpenetrating extracellular cryoprotectant. In contrast to glycerol, it does not require labor-intensive removal from thawed red blood cells (RBCs) prior to transfusion. In this study, we compared glycerol and HES, and assessed HES as a substitute for glycerol in cryopreserved canine RBCs. The RBCs were preserved for 2 months in liquid nitrogen using a 20% (w/v) glycerol solution, and variable concentrations of HES solution. We evaluated the two cryoprotectants by the percentage of post-thaw hemolysis from the total free hemoglobin, saline stability, osmotic fragility, and by observing the erythrocyte morphology using a scanning electron microscope after thawing. The optimal concentration of HES was 12.5% (w/v) for the cryopreservation of canine RBCs. The thaw hemolysis, saline stability, and osmotic fragility index were 25.6 +/- 4.7%, 87.8 +/- 6.9%, and 0.445 +/- 0.024% NaCl respectively. These parameters resemble the results of RBCs frozen in a 20% (w/v) glycerol solution, which are 24.7 +/- 5.2%, 99.2 +/- 0.1%, and 0.485 +/- 0.023% NaCl respectively. From a morphological point of view, 12.5% (w/v) HES showed the best cryoprotection of RBCs compared to the other concentrations of HES. These results suggest that HES could be a possible substitute for glycerol for the cryopreservation of canine RBCs.     

Evaluation of techniques for counting bovine platelets.

Visual and electronic techniques for counting bovine platelets were investigated. The reference method used was hemacytometer counting of platelets in whole blood diluted with 0.85% NaCl solution. A whole blood platelet-rich plasma technique was imprecise and inaccurate. Isopycnic centrifugation of blood diluted in 8.01% NaCl solution (same density as platelets) was a precise technique, but the whole blood platelet count was underestimated. The most precise and accurate technique investigated was unit gravity sedimentation of a 1:100 dilution of blood with 10 ml of Isoton followed by electronic counting of platelets in the supernatant. This technique correlated very well with visual counting of bovine platelets (N = 77, y = 55 + 0.80x, r = 0.89, P less than 0.01).     

Comparison of microfilaria concentration method for Setaria digitata infection in cattle and for Dirofilaria immitis infection in dogs

Several peripheral blood microfilaria concentration methods that use Acetone (Acetone test), 2% formalin (modified Knott method), 5% Tween 20 solution, distilled water, 1% or 0.1% SDS were compared for their efficacy in detecting Setaria digitata microfilaria in cattle. The Acetone test was found to be more efficacious than the modified Knott method or the 5% Tween 20 solution test for detecting the S. digitata microfilaria in bovine blood. However, besides the Acetone test, the modified Knott method was also found to be suitable for Dirofilaria immitis microfilaria detection in dogs. SDS and distilled water were found not to be effective as hemolytic agent for the disruption of the red blood cell of both the cattle and dogs. Thus, the Acetone test is recommended for the primary screening of microfilaremia of S. digitata in cattle.     

Effects of dexamethasone and isoflupredone acetate on plasma potassium concentrations and other biochemical measurements in dairy cows in early lactation

OBJECTIVE: To determine whether administration of isoflupredone acetate (ISO) to healthy cows increases the frequency of severe hypokalemia and whether dexamethasone (DEX) has detectable mineralocorticoid properties. ANIMALS: 33 cows at 20 to 25 days of lactation. PROCEDURES: Cows were randomly allocated to 5 treatment groups and received 2 IM injections (on days 0 and 2) of sterile saline (0.9% NaCl) solution (10 mL each), an injection of ISO (20 mg) or DEX (20 mg) followed by 10 mL of saline solution, or 2 injections of ISO or DEX. Milk production was measured, physical examinations were performed, and blood and urine samples were collected daily on days 0 through 7. RESULTS: Physical examination parameters did not differ among groups; however, 1 cow developed atrial fibrillation on day 4. Both corticosteroids significantly increased plasma glucose concentrations, and ISO significantly decreased plasma potassium concentrations and increased total carbon dioxide concentrations with time. One dose of ISO decreased mean plasma potassium concentration by 25% on day 2, compared with day 0, and severe hypokalemia (serum potassium concentration < 2.3 mEq/L) developed in 1 of 6 cows. Mean plasma potassium concentration was 46% lower on day 3 than on day 0 in cows receiving 2 doses of ISO, and 5 of 7 cows became severely hypokalemic. Mean urinary fractional excretion of potassium significantly increased from that on day 0 in cows receiving 2 doses of ISO. CONCLUSIONS AND CLINICAL RELEVANCE: Both corticosteroids had glucocorticoid activity; however, only ISO had mineralocorticoid activity. Compared with saline solution, administration of 2 doses of ISO significantly increased the frequency of severe hypokalemia.     

A study on the effects of the rapid intravenous infusion of hypertonic Na and K solutions into normal conscious sheep on some cardiac characteristics and blood analytes.

Five normal, conscious, aged Merino ewes were infused with 200 ml of an aqueous solution containing 5% NaCl and 0.25% KCl (HNaK) at a mean rate of 0.024 ml/kg/s and four similar sheep with 0.9% saline at a mean rate of 0.018 ml/kg/s. Five ECG tracings were obtained over a 6-h period--two (20 s each) before, one (continuous tracing) during the infusion, and two (20 s each) afterwards. The heart was auscultated during the infusion. Seven heparinized blood samples were obtained--three before the infusion (1.5 h, 1.0 h, and immediately before), and four afterwards (immediately, 2.5 h, 4.5 h, and 24 h after). Determinations were made of changes in mean PCV, red cell counts, mean corpuscular volumes, plasma Na, K, Ca and Mg, and of erythrocyte Na and K concentrations. Analysis of variance revealed increases in heart rate when the results from both groups were combined, but no significant effects on cardiac rhythm. Auscultation revealed marked fluctuations in cardiac intensity within individual sheep and marked differences between sheep, particularly in those infused with HNaK. In the HNaK group there were significant increases in erythrocyte and plasma Na, and erythrocyte K and decreases in plasma Ca during the infusion. Plasma K increased from the termination of the infusion to 2.5 h afterwards in the saline group but decreased unexpectedly during the same period in the group infused with HNaK [corrected].     

The effects of 10% hypertonic saline, 0.9% saline and hydroxy ethyl starch infusions on hydro-electrolyte status and adrenal function in healthy conscious dogs

The purpose of this study was to investigate the influence of different saline and colloid solutions on adrenal steroid secretion in dogs. Six healthy male Beagles underwent three infusion cycles: 10 min infusion of 30 ml/kg of NaCl 0.9%, 5 ml/kg of hydroxy ethyl starch, or 5 ml/kg of NaCl 10%. Plasma osmolality, hematocrit, total solids, cortisol and aldosterone levels were measured at 0, 5, 15, 30, 60, 120, 180 and 240 min after beginning infusion. Plasma ACTH levels were measured at 0, 15 and 240 min. An identical timing of sampling was applied during a control session omitting the fluid infusion. Osmolality, sodium, chloride and cortisol levels were found to be significantly higher with hypertonic saline solute compared to control. All fluid infusions lead to lowered plasma potassium, hematocrit, total solids and aldosterone values. ACTH concentrations did not show significant changes with any of the infusion cycles. The increase in cortisol levels suggests that hypertonic saline infusion could be interesting in critical care resuscitation, particularly in patients who are suffering from relative adrenal insufficiency.     

Cardiopulmonary effects of an intravenous infusion of guaifenesin, ketamine, and xylazine in dogs

A 5% solution of dextrose in water containing 50 mg of guaifenesin, 0.25 mg of xylazine, and 1 mg of ketamine/ml was infused IV at the rate of 2.2 ml X kg-1 X hour-1 in dogs. Heart rate, systemic vascular resistance, mean arterial blood pressure, rate-pressure product, and arterial oxygen tension were not altered significantly from baseline values during 2 hours of anesthesia. Cardiac index was significantly (P less than 0.05) decreased from base-line values. Hypoventilation resulted in increased arterial carbon dioxide tension and decreased arterial pH. After the dogs were given glycopyrrolate, cardiac index returned to base line, and heart rate, mean arterial pressure, and rate-pressure product were significantly greater (P less than 0.05) than base-line values.     

Concentrations of penicillin, streptomycin, and spiramycin in bovine udder tissue liquids

Concentrations of benzylpenicillin and spiramycin adipate were determined in bovine plasma and milk and in lymph draining the udder tissue after IM or IV administration. Combined benzylpenicillin and dihydrostreptomycin sulfate concentrations were also determined in the same fluids after intramammary injection. A superficial parenchymal lymph vessel, afferent to the supramammary lymph gland of the left quarters, was cannulated with a polythene catheter from which the lymph was allowed to drain freely. After injections of 9.5 mg of benzylpenicillin/kg of body weight IM, a mean peak concentration (PC) in lymph (3.7 micrograms/ml), constituting 77% of the PC in plasma (4.8 micrograms/ml), was obtained 0.5 to 1 hour after PC in the plasma. The benzylpenicillin lymph concentration was close to that in plasma for about 7 hours after injection. Thereafter, the benzylpenicillin lymph concentration continued to exceed that in plasma, but not that in milk. After IV administration of spiramycin adipate, the lymph concentration was almost identical to that in plasma. After intramammary injection of procaine benzylpenicillin (400 mg), in combination with the same amount of dihydrostreptomycin sulfate, into 2 udder quarters each, mean PC in the lymph of 3.5 micrograms/ml and 8.4 micrograms/ml, respectively, were obtained 6 hours after injection. In plasma, the mean PC of benzylpenicillin (0.07 micrograms/ml) and of dihydrostreptomycin sulfate (0.85 micrograms/ml) were obtained after 4 and 6 hours, respectively. In milk from the nontreated quarters, a mean concentration of 5 ng of benzylpenicillin/ml was obtained, whereas dihydrostreptomycin sulfate (greater than or equal to 0.3 microgram/ml) was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenous administration of lidocaine on the thermal threshold in cats

OBJECTIVE: To determine the effects of IV administration of lidocaine on thermal antinociception in conscious cats. ANIMALS: 6 cats. PROCEDURE: 2 experiments were performed in each cat (interval of at least 2 months). In experiment 1, lidocaine pharmacokinetics were determined for each conscious cat following IV administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from experiment 1 were used to calculate appropriate doses of lidocaine that would achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL. Skin temperature and thermal threshold were determined at the start of the experiment (baseline) and at each concentration. Samples of venous blood were obtained at each target concentration for plasma lidocaine concentration determination. RESULTS: In experiment 2, actual plasma lidocaine concentrations were 0.00 +/- 0.00 microg/mL, 0.25 +/- 0.18 microg/mL, 0.57 +/- 0.20 microg/mL, 1.39 +/- 0.13 microg/mL, 2.33 +/- 0.45 microg/mL, and 4.32 +/- 0.66 microg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL, respectively. Compared with baseline values, no significant change in skin temperature or thermal threshold was detected at any lidocaine plasma concentration (or saline solution equivalent). Skin temperature or thermal threshold values did not differ between lidocaine or control treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that these moderate plasma concentrations of lidocaine did not affect thermal antinociception in cats.     

Effects of long-term administration of recombinant bovine tumor necrosis factor-alpha on glucose metabolism and growth hormone secretion in steers

OBJECTIVE: To investigate the effects of long-term administration of recombinant bovine tumor necrosis factor-alpha (rbTNF) on plasma glucose and growth hormone concentrations, and to determine whether treatment with rbTNF causes insulin resistance in steers. ANIMALS: 5 steers treated with rbTNF and 5 steers treated with saline (0.9% NaCl) solution (control). PROCEDURES: In experiment 1, rbTNF (5.0 microg/kg of body weight) or saline solution (5 ml) was administered SC daily for 12 days. Blood samples were obtained before treatment, and plasma was harvested for determination of glucose, insulin, and growth hormone (GH) concentrations. In experiment 2, insulin, glucose, or growth hormone-releasing hormone (GHRH) was administered IV on days 7, 9, and 11, respectively, after initiation of rbTNF or saline treatment in experiment 1. Plasma glucose and insulin concentrations were measured before and at various times for 4 hours after insulin or glucose administration. Plasma GH concentrations were measured at various times for 3 hours after GHRH administration. RESULTS: In experiment 1, administration of rbTNF resulted in hyperinsulinemia without hypoglycemia and decreased plasma GH concentrations. In experiment 2, plasma glucose concentrations were higher in steers treated with rbTNF and insulin than in controls. Plasma GH concentrations were lower in steers treated with rbTNF and GHRH than in controls. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged treatment with rbTNF induced insulin resistance and inhibited GHRH-stimulated release of GH in steers. Results indicate that rbTNF is a proximal mediator of insulin resistance and inhibits release of GH during periods of endotoxemia or infection.     

Tumor necrosis factor as a potential mediator of acute metabolic and hormonal responses to endotoxemia in calves

The effects of coliform endotoxin (E) and recombinant bovine tumor necrosis factor alpha (TNF) were compared with respect to clinical signs of disease and changes in plasma metabolite and pituitary and pancreatic hormone concentrations in calves. In addition, changes in plasma TNF concentration during each challenge exposure were quantitated by use of radioimmunoassay. Healthy Holstein bull calves with mean body weight of 90 kg were each given, in order, on different days, saline solution (5.0 ml, IV, day 1, n = 4), E (type 055:B5, 1.0 micrograms/kg of body weight IV, day 2, n = 4) and TNF (5.0 micrograms/kg IV, day 9, n = 3). Jugular venous blood samples, rectal temperature reading, and PCV were obtained at hourly intervals before (2 hours) and after challenge exposure. The PCV increased (P less than 0.05) after E and TNF administrations for the first 5 hours, then returned to normal in calves given E, but decreased and remained low in calves given TNF through 24 hours. Plasma triglyceride and nonesterified free fatty acids concentrations were increased through 10 hours (P less than 0.05) after E administration, whereas triglyceride and nonesterified free fatty acids concentrations were not significantly affected by TNF administration. Increase in blood glucose concentration at 1 hour after administration of E and TNF was followed by prolonged hypoglycemia that lasted through 6 hours. Changes in plasma insulin concentration paralleled the observed changes in glucose concentration, initially increased at 2 hours after E and TNF (P less than 0.05) administrations, but then tended to decrease below control values thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)