Radionuclide angiocardiography in the normal dog: first-pass studies

The first pass of a bolus of radioactivity (99mTc) through the heart and lungs was studied in 27 anaesthetised healthy adult mongrel dogs, using a gamma camera with a computer on-line. Bodyweights ranged from 9 to 60 kg, heart rate from 108 to 150 beats min-1. Quantitative analysis revealed that the distribution volume (DV) of the labelled blood, the cardiac output (CO), the stroke volume (SV) and pulmonary blood volume (PBV) were almost proportional to the bodyweight. Specific results were: DV 120 ml kg-1, CO 136 ml kg-1, SV 1.11 ml kg-1, PBV 6.9 ml kg-1. The pulmonary transit time varied between 1.0 and 3.6 seconds. Clinical applicability of the method, including visual inspection of camera images and quantitative analysis of a time-activity curve of the lung, was demonstrated for one dog with an aortic stenosis and another with a left-to-right shunt.     

Thermodilution cardiac output determination in the guinea pig

Thermodilution cardiac output was compared with simultaneously determined aortic flow in 5 guinea pigs during thoracotomy. Total cardiac output was affected by volume expansion, adrenergic stimulation, and the volume of hemorrhage. For the equation y = mx, where y is aortic flow, x is thermodilution cardiac output, and m is the slope of the regression line, m = 0.88 +/- 0.02 (95% confidence interval). The SE of the regression was 27.8 ml/min. Thermodilution may have been overestimated because the aortic flow measurement did not take into account the coronary arterial blood flow, which is approximately 4% of total cardiac output in the guinea pig. Indicator loss (ie, temperature) also may be an important factor in the calculation of cardiac output, as determinations of thermodilution cardiac output were affected by sampling site in the guinea pig. Thermodilution appears to be a useful and reliable means of determining cardiac output in the guinea pig.     

Disposition kinetics and dosage regimen of ceftriaxone in crossbred calves (short communication).

Disposition kinetics and urinary excretion of ceftriaxone were investigated in healthy crossbred calves after its single intravenous administration (10 mg kg-1). Based on kinetic parameters, an appropriate dosage regimen of ceftriaxone in calves was calculated. The peak plasma level of ceftriaxone at 1 min was 84.0 +/- 1.55 micrograms ml-1 which declined to 0.43 +/- 0.05 microgram ml-1 at 8 h. The value of elimination half-life (t1/2 beta), volume of distribution Vd (area) and total body clearance (ClB) were 4.39 +/- 0.63 h, 1.91 +/- 0.19 L kg-1 and 0.31 +/- 0.01 L kg-1 h-1, respectively. Approximately 41 per cent of total administered drug was recovered in the urine within 24 h of its administration. The plasma protein binding of ceftriaxone was found to be concentration dependent with an overall mean of 38.55 per cent. The binding capacity of ceftriaxone to plasma proteins and the dissociation rate constant of protein-drug complex were 20.1 x 10(-8) +/- 18.4 x 10(-8) mole g-1 and 1.07 x 10(-6) +/- 0.52 x 10(-6) mole, respectively. An appropriate intravenous dosage regimen of ceftriaxone in cattle would be 12 mg kg-1 repeated at 24 h.     

Pharmacokinetics and bioavailability of spiramycin in pigs.

The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/- 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species.     

In utero infection with porcine reproductive and respiratory syndrome virus modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid of surviving piglets

It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8(+) cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8(+) cells in 2-week-old infected piglets (33.4 +/- 12.6%) was followed by a decline to 7.3 +/- 3.0 and 11.1 +/- 3.0% at 4 and 6 weeks of age. BALF of control piglets contained 1.6 +/- 0.9, 2.3 +/- 1.8 and 1.9 +/- 0.5% CD8(+) cells, only. In peripheral blood, however, the average number of CD8(+) cells remained at high levels in the infected piglets throughout the post-natal experimental period (2.8 +/- 1.9, 2.9 +/- 1.8 and 3.2 +/- 1.7 x 10(6) CD8(+) cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8(+) cells were 0.9+/-0.2, 1.9 +/- 1.7 and 1.6 +/- 0.5 x 10(6)/ml, respectively. Furthermore, the numbers of CD2(+) , CD4(+)CD8(+) and SLA-classII(+) cells, respectively, in peripheral blood, together with the levels of CD2(+) and CD3(+) cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls.The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8(+) cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV.     

Disposition kinetics and dosage of cephaloridine in calves

The disposition kinetics and dosage regimen of cephaloridine were investigated in calves following a single intravenous dose of 10 mg.kg-1. The distribution half-life and elimination half-life were 0.16 +/- 0.02 and 1.96 +/- 0.16 h, respectively. The apparent volume of distribution was 0.64 +/- 0.06 l.kg-1 and total body clearance which represents the sum of all clearance processes, was 225.2 +/- 15.1 ml.kg-1.h-1. Based on kinetic parameters, a satisfactory intravenous dosage regimen of cephaloridine in calves would be 11.0 mg.kg-1 repeated every 8 h.     

Effects of allopurinol in experimental endotoxin shock in horses

The effect of allopurinol pretreatment 12 hours before an intraperitoneal challenge with a sublethal dose of Escherichia coli endotoxin (50 micrograms kg-1) was evaluated in 18 horses. The horses were divided among three equal groups: 1-endotoxin alone; 2-5 mg allopurinol kg-1 bodyweight plus endotoxin; and 3-50 mg allopurinol kg-1 bodyweight plus endotoxin. A variety of evaluation parameters were used. No differences among the groups were noted in rectal temperature, heart rate, respiration rate, haematological values, blood PaO2, blood PaCO2, blood pH or blood bicarbonate. Significant (P less than 0.05) differences between the groups were noted as regards the changes in capillary refill time, base excess, blood glucose, blood lactate, blood beta-glucuronidase and recumbency time. The protection afforded by 5 mg allopurinol kg-1 appeared to be superior to that with 50 mg allopurinol kg-1.     

Tannic acid intoxication in sheep and mice

Acute tannic acid intoxication was studied in mice and sheep. In mice, following oral administration of 2.0 to 4.6 g of tannic acid kg-1 bodyweight, periacinar coagulative and haemorrhagic necrosis occurred in the liver. In sheep, following oral (8 g kg-1 bodyweight) administration of tannic acid, liver necrosis was not observed either histologically or detected biochemically, although transmission electron microscopy showed focal hepatocellular necrosis, steatosis and acicular crystal cleft formation. In sheep given tannic acid intraperitoneally (0.1 g kg-1 bodyweight), liver necrosis occurred and plasma sodium and glucose levels significantly (P < 0.05) decreased while packed cell volume and plasma aspartate aminotransferase, alkaline phosphatase, creatinine and bilirubin significantly (P < 0.01) rose. The results for blood-gas and acid-base determinations, blood haemoglobin and oxygenation showed significant increases in arterial blood methaemoglobin concentration (P < 0.05) and decreases in blood pH (P < 0.01) and oxyhaemoglobin concentration (P < 0.05) in sheep by 32 hours after oral dosing with 8 g of tannic acid kg-1 bodyweight. In sheep given tannic acid intraperitoneally, methaemoglobinaemia was not detected, but metabolic acidosis with a compensatory respiratory alkalosis occurred. Thus, it would appear that although tannic acid is hepatotoxic when given orally to mice or intraperitoneally to sheep, it does not produce renal or significant hepatic injury in sheep when given orally, but rather causes metabolic acidosis and methaemoglobinaemia.     

Pharmacokinetics of ceftazidime in sheep and its penetration into tissue and peritoneal fluids

Serum, tissue and peritoneal fluid concentrations of ceftazidime were studied in ewes after intravenous, intramuscular and subcutaneous administration at 50 mg kg-1 bodyweight. Tissue and peritoneal cages were implanted in the animals studied. After intravenous bolus administration, the mean serum concentration versus time profile was best described by a two-compartment open model. The distribution rate constant (alpha) was 3.5 +/- 1.1 h-1 and the half-life (t 1/2 alpha) 0.22 +/- 0.09 hour. The elimination rate constant (beta) was 0.43 +/- 0.04 h-1 and half-life (t 1/2 beta) 1.6 +/- 0.2 hours. The area under the curve was 275.7 +/- 84.0 micrograms.ml-1 h. The volume of distribution as steady state was 356.1 +/- 208.0 ml kg-1. The penetration ratio into tissue fluid was 62.6 +/- 15.1 per cent and into peritoneal fluid 61.1 +/- 16.5 per cent. After intramuscular injection, the elimination half-life was 1.7 +/- 0.2 hours, the area under the curve was 228.7 +/- 43.3 micrograms.ml-1 h. and the elimination rate constant was 0.42 +/- 0.05 h-1. The penetration ratio into tissue fluid was 68.5 +/- 37.3 per cent and into peritoneal fluid 73.3 +/- 34.4 per cent. After subcutaneous injection, the elimination half-life was 1.8 +/- 0.5 hours, the area under the curve was 231.8 +/- 65.6 micrograms.ml-1 h. and the elimination constant was 0.41 +/- 0.10 h-1. The penetration ratio into tissue fluid was 47.2 +/- 3.5 per cent and into peritoneal fluid 58.1 +/- 15.6 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Benzylpenicillin kinetics in the ewe: influence of pregnancy and lactation

Benzylpenicillin kinetics were investigated in a breed of sheep adapted to life in barren areas. Important pharmacokinetic differences, dependent on reproductive status (control, pregnancy, lactation), were demonstrated. In control ewes, the steady state volume of distribution was 0.23 +/- 0.15 litre kg-1 and the plasma clearance was 12.4 +/- 3.19 ml kg-1 min-1. During pregnancy, these two parameters were not significantly modified. During lactation, the plasma clearance and volume of distribution were significantly higher than during the control period and pregnancy (27.4 +/- 3.22 ml kg-1 min-1 and 0.696 +/- 0.20 litre kg-1, respectively (P less than 0.01). In contrast the mean residence time (25.0 +/- 4.6 minutes) was similar to those of the control period (17.54 +/- 6.25 minutes) and pregnancy (23.18 +/- 5.94 minutes). These modifications in benzylpenicillin kinetics were explained in terms of fluid balance adjustments and renal function adaptation observed during pregnancy and lactation, and it is suggested that an appropriate dosage regimen for benzylpenicillin should take into account the physiological status of the animal.     

Pharmacokinetics, urinary excretion and dosage regimen of diminazene in crossbred calves

The pharmacokinetics, urinary excretion and dosage regimen of diminazene were investigated in crossbred male calves following a single intramuscular dose (3.5 mg x kg-1). Following intramuscular administration, the pharmacokinetics of diminazene was described with a one-compartment open model. The absorption rate constant and absorption half-life were 9.86 +/- 3.06 h-1 and 0.121 +/- 0.40 h, respectively. The value of elimination half-life was 107.5 +/- 8.50 h. The apparent volume of distribution was 0.74 +/- 0.07 L x kg-1. Systemic availability following intramuscular administration was 91.7%. Approximately 65% of the administered dose of diminazene was eliminated in the urine within 24 h of its intramuscular administration. Diminazene was bound to plasma proteins to the extent of approximately 32%. The satisfactory intramuscular dosage regimen of diminazene for calves would be 2.24 mg x kg-1 followed by 1.5 mg x kg-1 at 7 days.     

Altered disposition of propylthiouracil in cats with hyperthyroidism

The oral and intravenous disposition of the anti-thyroid drug propylthiouracil (PTU) was determined in six clinically healthy cats and four cats with naturally occurring hyperthyroidism. Compared with the normal cats, the mean plasma elimination half-life of PTU was significantly (P less than 0.001) shorter in the hyperthyroid cats (77.5 +/- 5.8 minutes compared with 125.5 +/- 3.7 minutes) and the total body clearance of PTU was significantly (P less than 0.05) more rapid in the cats with hyperthyroidism (5.1 +/- 0.8 ml kg-1 min-1 compared with 2.7 +/- 0.2 ml kg-1 min-1). Following oral administration, both the bioavailability (59.7 +/- 4.9 per cent compared with 73.3 +/- 3.7 per cent) and peak plasma concentrations (14.5 +/- 1.6 micrograms ml-1 compared with 18.9 +/- 0.9 micrograms ml-1) of PTU were significantly (P less than 0.05) lower in the hyperthyroid cats than in the control cats. No difference was noted, however, between the apparent volume of distribution for PTU in the two groups of cats. Overall, results of this study indicate that the oral bioavailability of PTU is decreased and PTU disposition is accelerated in cats with hyperthyroidism.     

Effects of Draft Loaded Training on Circulatory and Blood Lactate Responses During Exercise in Horses

Five Standardbred trotters were trained on a treadmill 3 times as week for 12 weeks by intervals of draft loaded exercise. The draft load was 34 kilopond and the velocity approximately 7 m/sec -1. Standardized exercise tests with sequentially increasing speed were performed before, and after 4, 8 and 11 weeks of training. No significant effects of training were seen on heart rate response to exercise or on total blood volume, red cell volume and plasma volume when related to bodyweight, whereas less blood lactate (p<0.05) was accumulated. Blood lactate response to exercise may therefore be valuable for monitoring metabolic adaptations to training by draft loaded exercise.     

Xylazine-induced hyperglycemia in beef cattle.

Intravenous administration of xylazine to beef cattle (10 animals, 0.2 mg/kg of body weight) resulted in rapid onset (less than 15 minutes) of hyperglycemia. Plasma glucose values increased to 195 +/- 15 mg/dl and 305 +/- 10 mg/dl at 15 minutes and 3 hours, respectively. Concomitantly, plasma insulin concentrations dropped from 23 +/- 2 microU/ml before xylazine to 5.8 +/- 0.7 microU/ml and 2.4 +/- 0.3 microU/ml at 15 minutes and 3 hours, respectively. Parallel decreases (20%) were observed for percentage of hemoglobin, red blood cell number, and packed cell volume. Plasma urea nitrogen was significantly (P less than 0.01) incrased within 3 hours of xylazine administration (6.7 +/- 0.9 mg/dl vs 11.4 +/- 0.7 mg/dl). Marked changes in concentrations of plasma-free fatty acids were not observed. Alternative means of anesthesia must be considered in those instances in which biopsy material is to be used for studies of carbohydrate metabolism in vitro.     

Assessment of blood glutathione peroxidase activity in the dromedary camel

Blood glutathione peroxidase (GSH-Px) levels in 709 normal dromedary camels (442 females and 267 males) were assessed in the Canary Islands. All animals were intensively reared, and three different nutritional systems were evaluated, depending on selenium content of the diet. Mean GSH-Px level in the total population was 288.5+/-157.2 IU x g(-1) Hb. Reference ranges were estimated and enzymatic activities below 51 IU x g(-1) Hb were considered inadequate. GSH-Px activities obtained in females (298.1+/-155.7 IU x g(-1) Hb) were significantly (P = 0.037) higher than in males (272.6+/-157.2 IU x g(-1) Hb). When age groups were compared, only males between 6 and 12 months old exhibited significantly lower mean GSH-Px (P = 0.006) than females. A high correlation (r = 0.88) between serum selenium concentration and blood GSH-Px activity was estimated, and the regression equation was y = 2.5101x + 42.423. Selenium content of the diet above 0.1 mg x kg(-1) DM seems to supply adequate selenium requirements for dromedaries under intensive husbandry.     

Effects of a highly concentrated hypertonic saline-dextran volume expander on cardiopulmonary function in anesthetized normovolemic horses.

Conventional fluid resuscitation is unsatisfactory in a small percentage of equine emergency surgical cases because the large volumes of fluids required cannot be given rapidly enough to adequately stabilize the horse. In anesthetized horses, the volume expansion and cardiopulmonary effects of a small volume of highly concentrated hypertonic saline-dextran solution were evaluated as an alternative initial fluid choice. Seven halothane-anesthetized, laterally recumbent, spontaneously ventilating, normovolemic horses were treated with a 25% NaCl-24% dextran 70 solution (HSD) at a dosage of 1.0 ml/kg of body weight, IV, infused over 10 minutes, and the effects were measured for 120 minutes after infusion. Plasma volume expansion was rapid and significant (from 36.6 +/- 4.6 ml/kg to 44.9 +/- 4.8 ml/kg), and remained significantly expanded for the duration of the experiment. Packed cell volume, total blood hemoglobin, and plasma protein concentrations significantly decreased, confirming rapid and sustained volume expansion with hemodilution. Cardiac index and stroke index immediately increased and remained high for the entire study (from 69.6 +/- 15.3 ml/min/kg to 106.6 +/- 28.4 ml/min/kg, and from 1.88 +/- 0.49 ml/beat/kg to 2.50 +/- 0.72 ml/beat/kg, respectively). Systemic vascular resistance significantly decreased immediately after HSD infusion and remained decreased for the duration of the study (from 1.41 +/- 0.45 mm of Hg/ml/min/kg to 0.88 +/- 0.22 mm of Hg/ml/min/kg). Arterial and venous blood oxygen content decreased significantly because of hemodilution, but actual oxygen transport transiently increased at the 10-minute measurement before returning toward baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal clearance of endogenous creatinine and urea in sheep during summer and winter

Simultaneous measurement of the renal clearance of endogenous creatinine and exogenous inulin in eight sheep showed similar mean +/- SD (n = 32) values of 13.8 +/- 1.3 and 13.2 +/- 2.0 ml min-1 (10 kg)-1 bodyweight respectively. These results demonstrate that the renal clearance of endogenous creatinine is a satisfactory measure of glomerular filtration rate (GFR) in sheep. The plasma concentrations of endogenous creatinine and urea were significantly higher because of haemoconcentration during summer, resulting in lower GFR than in winter. Besides glomerular filtration and back diffusion, the renal handling of urea in sheep seems to involve mechanisms analogous to active tubular secretion.     

Pharmacokinetics of single doses of cefoperazone given by the intravenous and intramuscular routes to unweaned calves

Cefoperazone pharmacokinetics were studied in unweaned calves. The antibiotic was administered to 10 calves intravenously, to eight calves intramuscularly at 20 mg kg-1 and to 10 calves intramuscularly at 20 mg kg-1 together with probenecid at 40 mg kg-1. Serum concentration versus time data were analysed by non-compartmental methods based on the statistical moment theory. The intravenous data were also fitted by a linear, open two-compartment model. The terminal halflife of cefoperazone was 127.9 +/- 28.2 min (mean +/- SD) after intravenous and 136.9 +/- 19.6 min after intramuscular administration. The t1/2 was increased to 257.3 +/- 127.3 min by the co-administration of probenecid. The total body clearance was 8.16 +/- 1.60 ml min-1 kg-1 and the volume of distribution at steady state was 0.713 +/- 0.167 litre kg-1. The mean residence time values were 87.2 +/- 10.6 min after intravenous and 140.3 +/- 20.6 min after intramuscular injection and were increased to 264.5 +/- 99.8 min by the co-administration of probenecid. The estimated mean absorption time was 53.1 min and the estimated bioavailability after intramuscular administration was 76.3 per cent. The minimal inhibitory concentration (MIC90) values of cefoperazone ranged from 0.5 to 2 micrograms ml-1 for Escherichia coli, salmonella groups C, D and E and Pasteurella multocida isolates. Salmonella group B strains appeared to be highly resistant to cefoperazone with MIC90 greater than 32 micrograms ml-1. There were no significant differences between the pharmacokinetic variables calculated by statistical moment theory or compartmental analysis indicating central compartment output of cefoperazone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flumequine in the Goat: Pharmacokinetics after Intravenous and Intramuscular Administration

The pharmacokinetics of flumequine, administered intravenously and intramuscularly at a single dose of 20 mg/kg, was investigated in healthy goats. After intravenous injection, flumequine distributed rapidly (t1/2alpha = 0.87+/-0.15 h) but was eliminated slowly (t1/2beta = 7.12+/-1.27 h); mean clearance (Cl) and volume of distribution (Vdss) were 0.32+/-0.03 (L/(h x kg) and 1.22+/-029 (L/kg), respectively. After intramuscular administration, the peakserum concentration (Cmax = 7.40+/-0.5 microg/ml) was reached in about 1.5 h (Tmax) and bioavailability was about 93%. Estimated flumequine serum levels following repeated intramuscular administration of the aqueous suspension used in the study (7.23+/-0.7 microg/ml and 4.82+/-0.47 microg/ml at intervals of 8 and 12 h, respectively) indicated that to maintain serum levels above MIC values for susceptible bacteria a dosage regimen of 20 mg/kg every 12 h is necessary by the intramuscular route.