Renal electrolyte and net acid excretion were characterized during generation and maintenance of hypochloremic metabolic alkalosis in a ruminant model. Two phases of renal response with regard to sodium and net acid excretion were documented. An initial decrease in net acid excretion was attributable to increase in bicarbonate excretion with associated increase in sodium excretion. As the metabolic disturbance became more advanced, a second phase of renal excretion was observed in which sodium and bicarbonate excretion were markedly decreased, leading to increase in net acid excretion and development of aciduria. Throughout the metabolic disturbance, chloride excretion was markedly decreased; potassium excretion also decreased. These changes were accompanied by increase in plasma renin and aldosterone concentrations. There was apparent failure to concentrate the urine optimally during the course of the metabolic disturbance, despite increasing plasma concentration of antidiuretic hormone.

Canine gastric dilatation-volvulus (GDV) is a naturally acquired condition of large-breed dogs primarily and is associated with high mortality. The clinical course suggests that reperfusion injury may be important in the pathogenesis of GDV. To evaluate the role of xanthine oxidase and iron-dependent lipid peroxidation (which are purported mechanisms of reperfusion injury) in the pathogenesis of GDV-related mortality, we created experimental GDV in 21 dogs. These dogs were then treated with either allopurinol (a xanthine oxidase inhibitor), U74006F (an experimental lipid peroxidation inhibitor), or saline solution (NaCl, 0.85%). Three of 8 dogs died in the allopurinol-treated group, none of 5 died in the U74006F-treated group, and 4 of 8 died in the saline solution-treated group. Tissue malondialdehyde concentration, a nonspecific indicator of lipid peroxidation, was significantly (P < 0.05) greater in the duodenum, jejunum, colon, liver, and pancreas of the saline-solution treated and allopurinol-treated dogs than in the same tissues of the U74006F-treated dogs after surgical correction of the GDV (ie, during reperfusion), compared with malondialdehyde concentrations determined before inducing GDV. The results of this study support the concept that lipid peroxidation associated with reperfusion injury is important in the pathogenesis and high mortality of canine GDV. Furthermore, this lipid peroxidation and mortality may be preventable by appropriate and timely treatment.

A sublethal dose of ethylene glycol was administered orally to 3 groups of dogs; dogs of a control group were given distilled water instead. Renal cortical biopsy samples were obtained from dogs of experimental and control groups at various times after treatment. Tissue was examined by use of light microscopy and transmission electron microscopy. In dogs of the control group, the light and electron microscopic appearances of tissue were within normal limits at all sample collection hours. In dogs of the experimental groups, renal corpuscular structure remained within normal limits by use of light and electron microscopy throughout the study, though morphologic change was seen in other structures of the cortex. Light microscopic lesions first appeared at 12 hours, and were similar to those reported in the literature. Ultrastructural lesions were first observed in the 5-hour samples, and similar to the light microscopic lesions, were most common in the proximal convoluted tubules (PCT). Initial PCT cellular changes included vacuolization of cells and distention of the parabasal extracellular spaces; PCT cellular lesions seen in later-hour samples included formation of apical buds and cellular rupture. Internalization or sloughing of the PCT brush border was not observed. Distal convoluted tubules (DCT) were frequently dilated and/or packed with cellular debris. A few DCT cells had degenerative or necrotic changes. In PCT and DCT, abnormal cells were frequently flanked by normal or nearly normal cells. During later hours, a few cells with types of changes first observed in early hours continued to be observed, implying ongoing response of cells to the toxin.

Ceftiofur hydrochloride was tested for effectiveness against induced colibacillosis in neonatal swine. In this model, pigs < 12 hours old were inoculated via stomach tube with a virulent, K99+, nalidixic acid-resistant strain of Escherichia coli. Six hours after challenge exposure, 1 dose of ceftiofur was administered either IM or orally in experiment 1 and orally only in experiment 2. Mortality, shedding of bacteria, fecal consistency scores, and body weight changes were monitored for 10 days. In experiment 1 (n = 383 pigs), all treatments at dosage that ranged between 0.5 and 64.0 mg of ceftiofur/kg of body weight significantly (P < 0.001) reduced mortality, bacterial shedding, and diarrhea and increased weight gain, compared with findings in untreated controls. There were no detectable differences between oral and IM routes, except that there was greater reduction in bacteria shedding associated with the oral route of administration. In experiment 2 (n = 505 pigs), ceftiofur was administered orally either once at 6 hours after challenge exposure or twice at 6 and at 48 hours after the first dose. Dosage of ceftiofur was 0, 5, 10, 20, 30, or 60 mg/kg administered once, or half the same dose was administered at each of 2 times. At the optimal dosage (10 mg/kg), a single dose was as effective as 2 doses. The single administration at all dosages reduced mortality, bacterial shedding, and diarrhea scores and increased body weight gain, compared with findings in untreated pigs (P < 0.01). In this induced infection model, the optimal treatment dosage was determined to be 10 mg/kg administered once.

The effect of ingested epidermal growth factor (EGF) on the small intestinal mucosa of conventionally weaned pigs was determined. At 21 days of age, 39 pigs were randomly distributed into suckling and weaned treatment groups that were administered 124 micrograms of EGF, 372 micrograms of EGF, or the dosing compound daily. Fecal water content was determined daily. On postweaning days 0, 3, 6, and 9, representative pigs from each group were euthanatized, and jejunal mucosa samples were collected for determination of villus-to-crypt ratio, total protein content, disaccharidase activities, and microbiological populations. At postweaning day 3, the 372-micrograms dose of EGF significantly (P less than or equal to 0.05) increased jejunal lactase and sucrase activities in the weaned pigs. Increased lactase activity was not greater than that of the suckling pig controls, whereas sucrase activity was significantly (P less than or equal to 0.05) higher than that of the suckling pig controls. Significant changes were not observed in villus-to-crypt ratio, mucosal protein content, or disaccharidase activities on other collection days.

Plasma glucocorticoid concentrations and blood gas values were determined for 6 days in 47 newborn calves that had been subjected to various obstetrical procedures at term. Concentrations of glucocorticoids were uniformly high at birth (70 to 103 ng/ml). Increasing degrees of acidosis were accompanied by increasing glucocorticoid concentrations in plasma. Plasma glucocorticoid concentrations decreased sharply during the first 6 hours after delivery and reached a plateau at 48 hours after birth (14 to 21 ng/ml). The latter was taken as an indication that adaptation had been achieved. Calves subjected to severe pulling had higher glucocorticoid concentrations at birth (110.4 ng/ml) than calves requiring no assistance (88.3 ng/ml), calves requiring only slight assistance (83.8 ng/ml), or calves that had been delivered by cesarean section (82.9 ng/ml).

A single dose of digoxin was injected, IV, into 5 mature male turkeys (0.066 mg/kg of body weight), 8 male ducks (0.066 mg/kg), and 6 roosters (0.33 mg/kg). Twenty-three serial venous blood samples were collected before (baseline) and after the administration of digoxin to turkeys, ducks, and roosters. Plasma concentrations of digoxin were determined in duplicate by a radioimmunoassay that was validated for avian species. The plasma concentrations were best fitted by a 3 (turkeys, ducks)- and 2 (roosters)-compartment open model, with first-order elimination from the central compartment. Significant (P < 0.05) kinetic differences were determined among species. Mean half-life (t1/2) for ducks, roosters, and turkeys were 8.30 +/- 2.70 (mean +/- SD), 6.67 +/- 3.50, and 23.7 +/- 4.8 hours, respectively. The volume of distribution at steady state (V(SS)) was 14.7 +/- 2.9, 3.13 +/- 0.49, and 2.27 +/- 0.36 L/kg, and total body clearance (CL) of drug was 1.54 +/- 0.43, 0.461 +/- 0.187, and 0.136 +/- 0.022 L/h/kg for ducks, roosters, and turkeys, respectively. The mean residence time was 10.3 +/- 3.9, 8.37 +/- 4.97, and 16.8 +/- 2.2 hours, respectively. Volume of distribution at steady state and CL in ducks were several fold higher than that in turkeys. The terminal half-life of digoxin determined for ducks and roosters in this study was considerably shorter than those previously reported for several mammalian species.

Pharmacokinetic variables of etomidate were determined after IV administration of etomidate (3.0 mg/kg of body weight). Blood samples were collected for 6 hours. Disposition of this carboxylated imidazole best conformed to a 2- (n = 2) and a 3- compartment (n = 4) open pharmacokinetic model. The pharmacokinetic values were calculated for the overall best-fitted model, characterized as a mixed 2- and 3-compartmental model. The first and most rapid distribution half-life was 0.05 hour and a second distribution half-life was 0.35 hour. Elimination half-life was 2.89 hours, apparent volume of distribution was 11.87 +/- 4.64 L/kg, apparent volume of distribution at steady state was 4.88 +/- 2.25 L/kg, apparent volume of the central compartment was 1.17 +/- 0.70 L/kg, and total clearance was 2.47 +/- 0.78 L/kg/h.

Norepinephrine (NE) and epinephrine (EPI) collected from dogs were sequentially and temporally measured in blood and plasma at 24 C. Heparin and EDTA anticoagulants, in combination with reduced glutathione and EDTA as a preservative, were also compared. Norepinephrine and EPI concentrations were measured by high-pressure liquid chromatography with electrochemical detection. In heparinized plasma, NE and EPI concentrations were relatively stable in the absence or presence of preservative after 24 hours at 24 C. In EDTA plasma, NE and EPI values were less stable when compared with those in heparinized samples. Norepinephrine concentrations in EDTA plasma without preservative decreased by 163.2 +/- 8.88 pg over 24 hours, compared with an 86.6 +/- 7.92 pg loss of NE in heparinized plasma. The degradation of EPI in EDTA plasma without preservative was also twofold greater, compared with that in heparinized plasma. Addition of preservative had no stabilizing effect on NE or EPI in heparinized or EDTA plasma. During long-term storage at -70 C, plasma NE and EPI values decreased < 0.6 and < 0.1 pg/d, respectively. Norepinephrine and EPI values were stable in heparinized blood for 6 hours but decreased to < 25% and < 6% of initial base line values, respectively, when plasma separation was delayed 24 hours.

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of im absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 microgram/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 microgram/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 microgram/ml and maximal steady-state serum concentrations of 18.34 and 7.70 microgram/ml, respectively.