Comparison of various doses of carbon 13-labeled aminopyrine for a carbon 13-labeled aminopyrine demethylation blood test in healthy dogs

OBJECTIVE: To determine an optimal dose of carbon 13 ((13)C)-labeled aminopyrine for use in a (13)C-aminopyrine demethylation blood test in healthy dogs. ANIMALS: 9 adult dogs. PROCEDURES: Food was withheld from each dog for 12 hours. A 2-mL baseline blood sample was obtained from each dog and placed into an evacuated tube containing sodium heparin. Carbon 13-labeled aminopyrine was administered IV at doses of 1, 2, 5, or 10 mg/kg. Additional blood samples (2 mL) were obtained and placed into evacuated tubes containing sodium heparin 30, 45, 60, and 75 minutes after (13)C-aminopyrine administration. Hydrochloric acid was used to extract CO(2) from blood samples. The extracted gas was analyzed by fractional mass spectrometry to determine the percentage dose of (13)C administered as (13)C-aminopyrine and recovered in extracted gas (PCD). RESULTS: Gross evidence of clinical adverse effects was not detected in any dog after administration of (13)C-aminopyrine. The mean coefficient of variation (CV) for PCD was significantly lower than the mean CV for the summation of PCD values up to a given sampling time (CUMPCD). Mean PCD values among the 4 doses for each sample time were not significantly different. Administration of (13)C-aminopyrine at a dose of 2 mg/kg resulted in the lowest interindividual variability. CONCLUSIONS AND CLINICAL RELEVANCE: The PCD is superior to CUMPCD for the quantification of aminopyrine demethylation. Administration of (13)C-(13)C-aminopyrine at a dose of 2 mg/kg is appropriate for use in the (13)C-aminopyrine demethylation blood test in healthy dogs.     

Preliminary studies of a canine 13C-aminopyrine demethylation blood test.

The objectives of this study were to determine whether a 13C-aminopyrine demethylation blood test is technically feasible in clinically healthy dogs, whether oral administration of 13C-aminopyrine causes a detectable increase in percent dose/min (PCD) of 13C administered as 13C-aminopyrine and recovered in gas extracted from blood, and whether gas extraction efficiency has an impact on PCD. A dose of 2 mg/kg body weight of 13C-aminopyrine dissolved in deionized water was administered orally to 6 clinically healthy dogs. Blood samples were taken from each dog 0, 30, 60, and 120 min after administration of the 13C-aminopyrine. Carbon dioxide was extracted from blood samples by addition of acid and analyzed by fractional mass spectrometry. None of the 6 dogs showed any side effects after 13C-aminopyrine administration. All 6 dogs showed a measurable increase of the PCD in gas samples extracted from blood samples at 30 min, 60 min, and 120 min after 13C-aminopyrine administration. Coefficients of variation between the triplicate samples were statistically significantly higher for the %CO2, a measure of extraction efficiency, than for PCD values (P < 0.0001). The 13C-aminopyrine demethylation blood test described here is technically feasible. Oral administration of 13C-aminopyrine did not lead to gross side effects in the 6 dogs. Clinically healthy dogs show a measurable increase of PCD in gas extracted from blood samples after oral administration of 13C-aminopyrine. Efficiency of CO2 extraction from blood samples does not have an impact on PCD determined from these blood samples. This test may prove useful to evaluate hepatic function in dogs.     

Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease

The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.     

Kinetic analysis of demethylation of 13C-aminopyrine in healthy dogs

OBJECTIVE: To describe the kinetics of demethylation of 13C-aminopyrine in healthy dogs for use in determining the most appropriate time for collection of blood samples for a 13C-aminopyrine demethylation blood test for evaluation of hepatic function. ANIMALS: 9 healthy dogs. PROCEDURES: A 2-mL baseline blood sample was collected into an evacuated heparinized tube, and 13C-aminopyrine was administered to each dog (2 mg/kg, IV). Additional 2-mL blood samples were collected 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240, 300, and 360 minutes after 13C-aminopyrine administration. The CO2 was extracted from blood samples by addition of a strong acid, and the percentage dose of 13CO2 (PCD) in the extracted gas was determined by fractional mass spectrometry. RESULTS: No dogs had gross evidence of adverse effects, and all had an increase in PCD after IV administration of 13C-aminopyrine. The PCD had the least variability among 5 variables used to evaluate hepatic demethylating capacity. Peak PCD was detected at 30 minutes in 1 dog, 45 minutes in 5 dogs, 60 minutes in 2 dogs, and 75 minutes in 1 dog. The mean PCD for the 9 dogs peaked at 45 minutes after 13C-aminopyrine administration. CONCLUSIONS AND CLINICAL RELEVANCE: PCD appears to be the preferable variable for evaluation of hepatic demethylating capacity. Intravenous administration of 13C-aminopyrine leads to a consistent increase in PCD. Mean PCD peaked 45 minutes after administration, suggesting that blood sample collection 45 minutes after 13C-aminopyrine administration may be appropriate for use in estimating hepatic demethylating capacity.     

Changes in blood pressure following escalating doses of phenylpropanolamine and a suggested protocol for monitoring

This prospective, cross-over, blinded study evaluated the effect of various doses of phenylpropanolamine (PPA) on blood pressure in dogs. Dogs were randomized to receive a placebo or 1 of 3 dosages of immediate release PPA, q12h for 7 days [1 mg/kg body weight (BW), 2 mg/kg BW, or 4 mg/kg BW] in a cross-over design. Blood pressure was recorded every 2 h, for 12 h, on days 1 and 7. There were significant increases in systolic, diastolic, and mean blood pressure following administration of PPA at 2 mg/kg BW and 4 mg/kg BW. A significant decrease in heart rate was also noted at all PPA dosages, but not in the placebo. Administration of PPA was associated with a dose response increase in blood pressure. Dosages of up to 2 mg/kg BW should be considered safe in healthy dogs.     

Effectiveness and disposition of the newly developed cephalosporin cefquinome in puerperal septicemia and toxemia in gilts]

Epizootiological, clinical, bacteriological and haematological studies were carried out to assess the effectiveness of the recently developed cephalosporin preparation Cefquinome in the treatment of the puerperal septicaemia and toxaemia syndrome. Cefquinome was administered at three different doses (1, 2 and 4 mg/kg BW) to 188 sows with feverish puerperal illness. Amoxicillin (7 mg/kg BW) was used as a control drug. In 41% of cases endometritis was a monoinfection whereas in 70% of mammary infections mixed infections were diagnosed. Results showed that for therapy of puerperal septicaemia and toxaemia Cefquinome at doses of 2 mg/kg BW and 4 mg/kg BW is clearly more effective than the control drug Amoxicillin and Cefquinome at its lowest dose of 1 mg/kg BW.     

Technical note: effect of corticotropin-releasing hormone on adrenocorticotropic hormone and cortisol in steers

The objective of this study was to determine an appropriate exogenous dose of bovine corticotropin-releasing hormone (bCRH) to stimulate the physiological effects of the hypothalamic-pituitary-adrenal axis in steers as a method to test the sensitivity of the pituitary and adrenal gland. Twenty 14-mo-old Holstein-Friesian steers were blocked by weight (443.7+/-2.5 kg) and randomly allotted to receive either saline (control) or bCRH (0.1, 0.3, 1.0, or 1.5 microg/kg BW). Animals were housed in a slatted-floor facility (n = 5 per pen). Indwelling jugular catheters, for both the administration of bCRH and blood collection, were fitted on d -1 of the experiment. Saline and bCRH were administered i.v. at time 0. Serial blood samples were collected at -15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, and 180 min relative to time 0. Following administration of 0.1 microg of bCRH/kg BW, the peak ACTH response was not significantly different from pretreatment baseline concentrations (mean concentrations as measured at -15 and 0 min before bCRH administration). Mean ACTH concentrations from 0 to 180 min following 0.1 microg of bCRH/kg BW were not significantly different (P = 0.177) from controls. Administration of 0.3, 1.0, and 1.5 microg of bCRH/kg BW increased (P < 0.05) peak ACTH above pretreatment concentrations, and mean ACTH from 0 to 180 min for these treatments were greater (P < 0.05) than for controls. Peak cortisol responses to all bCRH treatments were greater (P < 0.05) than those to pretreatment concentrations. Mean cortisol concentrations from 0 to 180 min were greater (P < 0.05) in all bCRH-treated steers than in controls, but there were no significant differences among the bCRH treatments. The ratio of mean cortisol to mean ACTH for all bCRH doses tested differed (P < 0.05) from control values, indicating reactivity of the adrenals. In conclusion, bCRH challenge may be a useful method for testing the sensitivity of the hypothalamic-pituitary-adrenal axis in steers subjected to stressful husbandry conditions, and a minimum dose of 0.3 microg of bCRH/kg BW is required to stimulate physiological effects of stressor hormones.     

Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine

The experiments were conducted to determine the effects of the administration of growth hormone-releasing peptide-2 (GHRP-2, also named KP102), both orally by gavage and in feed, on the release of growth hormone (GH) in swine and to investigate whether attenuation of the GH response occurs after short-term treatment with the peptide in feed. In the first experiment, saline or GHRP-2 at doses of 1, 4.5 and 9 mg/kg body weight (BW) was dissolved in 15 ml saline and administered orally as a bolus by gavage to cross-bred castrated male swine (n = 6). Orally administered GHRP-2 stimulated dose-related increases in peak concentrations of GH, with a return to basal by 120 min. After administering GHRP-2 orally, peak concentrations of GH and areas under the GH response curves (GH AUCs) for 180 min were higher (P < 0.05) than those in saline controls. In Experiment 2, GHRP-2 at doses of 0 (served as control), 1, 4.5 and 9 mg/kg BW was mixed in 150 g of feed and offered to cross-bred castrated male swine (n = 6) at 0900 hr and 1700 hr daily for a 3-d period. Administration of 1 mg/kg BW GHRP-2 to swine in feed failed to stimulate the release of GH, but GHRP-2 at doses of 4.5 and 9 mg/kg BW significantly (P < 0.05) increased plasma concentrations of GH after initial and final treatments at 0900 hr on Days 1 and 3 of treatment, respectively. Peak concentrations of GH and GH AUCs for 180 min after the initial and final treatments in the 4.5 and 9 mg/kg BW GHRP-2-treated swine were higher (P < 0.05) than those in controls. After 3 d of treatment with GHRP-2 in feed at doses of 4.5 and 9 mg/kg BW, GH responses to the peptide were maintained. The results of the present study indicate that the administration of GHRP-2 orally by gavage and in feed stimulates the release of GH in swine, and that the GH-releasing effect of the peptide does not become desensitized after short-term administration in feed.     

Dose effect and benefits of glycopyrrolate in the treatment of bradycardia in anesthetized dogs.

This study evaluated the effectiveness of glycopyrrolate (0.005 or 0.01 mg/kg body weight (BW)) in anesthetized dogs (n = 40) for reversal of bradycardia (< 65 beats/min). Following random intravenous (i.v.) treatment, heart rate was determined at 5 min and, if it was < or = 70 beats/min, the lower dose was repeated. A 2-way analysis of variance considered dose and animal size (< or = 10 kg, > 10 kg) effects (P < 0.05). Glycopyrrolate produced a significant increase in heart rate and infrequent tachycardia (< or = 150 beats/min), which was not dose-related. The size of the dog produced a significant effect on baseline heart rate (higher in small), rate following the first dose (lower in small), and requirement for retreatment (47% in small, 13% in large). In a separate group of anesthetized dogs (n = 20), the blood pressure effect of glycopyrrolate (0.01 mg/kg BW, i.v.) treatment of bradycardia (65-85 beats/min, weight-adjusted) was studied. A significant increase in systolic, diastolic, and mean blood pressure was produced. In conclusion, the effective dose of glycopyrrolate treatment is size-related and produces a beneficial effect on blood pressure.     

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.     

Effect of anticholinergics (atropine, glycopyrrolate) and prokinetics (metoclopramide, cisapride) on gastric motility in beagles and labrador retrievers

The effect of atropine, glycopyrrolate, metoclopramide and cisapride on the antral motility was investigated in eight dogs (four Beagles and four Labradors) using passive telemetry. Both anticholinergics induced a pronounced and lasting reduction of the intensity and frequency of the contractions. A definite dose-related inhibition of the antral motility was seen in Beagles, similar for both active substances. Low doses of atropine (0.02 mg/kg BW i.m.) and glycopyrrolate (0.005 mg/kg BW i.m.) completely inhibited the gastric motility for at least 30 min, whereas higher doses (0.04 or 0.01 mg/kg BW) caused a cessation of activity for more than 3 h. In Labradors, the effects of both active substances were not so dose related and the effect of glycopyrrolate lasted at least 6 h, whereas the effect of atropine gradually decreased after 3 h. A distinct breed difference regarding the effect of the two prokinetics on the antral motility was also observed. In Beagles, the prokinetics, at a low dose (metoclopramide 0.3 mg/kg BW, cisapride 0.2 mg/kg BW), resulted in a significant increase in the amplitude integral. Higher doses (metoclopramide 0.6 mg/kg BW, cisapride 0.5 mg/kg BW) also increased the integrals of the pressure profiles, but significantly less than with the lower doses. In Labradors, both medications, mainly at higher doses, resulted in an increase of the contraction amplitudes. The low dose had no (cisapride) or only a transient effect (metoclopramide). The frequency of the antral contractions was not at all influenced by cisapride, and only in Beagles metoclopramide resulted in a dose-related increase. It is not clear if the different results in Labradors and Beagles are because of breed or body weight.     

Growth hormone response to growth hormone-releasing hormone in beef cows divergently selected for milk production

In dairy cattle, increased circulating growth hormone has been associated with selection for greater milk yield. This study tested the hypothesis that beef cows divergently selected for milk production would have differing GH responses to a challenge dose of GHRH. Growth hormone response to a challenge of GHRH was measured in 36 Angus-sired cows ranging from 6 to 10 yr of age. The cows were classified as high milking (n = 16) or low milking (n = 20), on the basis of their sires' milk EPD. Mean milk EPD (in kilograms) were 16.6 and -14.4 for high and low milking cows, respectively. Milk production was estimated by the weigh-suckle-weigh procedure. Blood samples were taken immediately before and 10 min after a clearance dose of 4.5 microg of GHRH/100 kg BW (injected i.v.) and, 3 h later, immediately before and 10 min after a challenge dose of either 1.5 or 4.5 microg of GHRH/100 kg BW. Each animal received both challenge doses, and the doses were randomly assigned across 2 d of blood collection. Serum concentrations of GH and IGF-I were measured by RIA. Serum IGF-I was measured in the baseline blood sample on d 1 of blood collection. A positive relationship (r = 0.35; P = 0.03) was observed between the cows' rankings for each dose of GHRH; that is, high responders to the low dose were high responders to the high dose. Growth hormone response to the 4.5 microg/100 kg BW challenge dose of GHRH was positively related to sire milk EPD (R2 = 0.09; P = 0.03). Response of GH to the 1.5 microg GHRH/100 kg BW challenge dose also tended to be related (P = 0.08) to sire milk EPD of high milking cows. In addition, IGF-I concentrations of high milking cows were inversely related (R2 = 0.24; P = 0.04) to sire milk EPD. Growth hormone response to GHRH challenge may have potential as an additional tool in the evaluation of milk production in beef cattle.     

The role of procaine in adverse reactions to procaine penicillin in horses

Procaine penicillin is a commonly used antibiotic in equine medicine but its use is associated with a substantial incidence of adverse reactions. Soluble procaine concentrations were determined by HPLC in several commercially available procaine penicillin preparations, including some that were involved in adverse reactions. The mean (+/- SEM) soluble procaine concentrations in the veterinary preparations was 20.18 +/- 5.07 mg/ml, which was higher than the concentration in the only procaine penicillin preparation for use in humans in Australia of 7.3 mg/ml. Heating the veterinary procaine penicillin preparations to 50 degrees C for 1 day led to a significant (P less than 0.01) increase in the amount of soluble procaine. Heating to 50 degrees C for 7 days also produced a significant (P less than 0.02) increase. Soluble procaine tended to return to baseline concentrations when veterinary procaine penicillin preparations were heated to 50 degrees C for 2 days then stored for 7 days at room temperature. Administration of procaine HCl intravenously (IV) at 2, 5, and 10 mg/kg produced behavioural, locomotor and vascular reactions, which were clinically similar to those reported in adverse reactions to procaine penicillin. The more severe reactions occurred at higher doses, although different horses responded variably at the same dose. Some adverse reactions lead to recumbency but none were fatal. The blood procaine concentrations 1 min after IV administration averaged 19.0 +/- 12.6 and 25.3 +/- 16 micrograms/ml at 2.5 mg/kg and 5 mg/kg, respectively. Ten min after administration, blood procaine concentrations were significantly higher (P less than 0.001) in the 5 mg/kg group than in the 2.5 mg/kg group. Intramuscular (IM) procaine HCl at 5 mg/kg produced significantly lower (P less than 0.001) blood concentrations than similar IV doses, and, in contrast to the IV doses, the amount of procaine in the blood was significantly higher 5 and 10 min after administration than it was after 1 min. Mild excitatory reactions in 4/5 horses were noted 5 to 10 min after IM administration. Administration of diazepam 20 s before procaine HCl prevented the excitatory adverse reaction in 2/2 horses, but administration after the procaine did not influence the outcome.     

Effects of intravenously administered glycopyrrolate in anesthetized horses.

The purpose of this study was to determine the heart rate (HR) and blood pressure (BP) effect of glycopyrrolate in anesthetized horses with low HR (< or = 30 beats/min). The horses were randomly treated with glycopyrrolate (2.5 micrograms/kg body weight (BW)) or saline, intravenously (i.v.) (n = 17). If HR failed to increase (by > 5 beats/min within 10 min), glycopyrrolate (same dose) was administered. Heart rate increased by > 5 beats/min in 3 out of 9 horses following the initial glycopyrrolate treatment. Overall changes in HR and mean BP were not significantly different, while systolic and diastolic BP increased significantly (P < 0.025 using a Bonferroni corrected paired t-test). On the 2nd treatment, 3 out of 7 horses given 2.5 micrograms/kg BW glycopyrrolate, and 4 out of 5 horses given 5.0 micrograms/kg BW (total dose) showed an increase in heart rate of > 5 beats/min, which was significant. A significant increase in BP was produced following treatment with 2.5 micrograms/kg BW, but not following 5.0 micrograms/kg BW. A final increase in HR, of > 5 beats/min, was associated with a significant rise in BP (P < 0.05 using an unpaired t-test). In conclusion, an increase in HR can occur with 2.5 to 5.0 micrograms of glycopyrrolate/kg BW, i.v., and results in improvement in BP in anesthetized horses.     

Sodium chlorate reduces the presence of Escherichia coli in feces of lambs and ewes managed in shed-lambing systems

Our objective was to establish doses of orally administered NaClO(3) that reduced the presence of generic Escherichia coli in intestines of ewes and neonatal lambs managed in a shed-lambing system. Neonatal lambs (n = 32; age = 7.1 ± 1.2 d; BW = 6.8 ± 1.0 kg) and yearling ewes (n = 44; BW = 74.8 ± 5.6 kg) were used in 2 experiments. In both experiments, lambs and ewes were randomly assigned to 1 of 4 groups, and groups were randomly assigned to 1 of 4 treatments. In Exp. 1, neonatal lambs were given single, aqueous, oral doses of saline (control; NaCl, 30 mg·kg of BW(-1)) or 30, 60, or 90 mg of NaClO(3)·kg(-1) of BW. At 25.9 ± 1.3 h after treatment, lambs were euthanized, and intestinal contents were collected aseptically. In Exp. 2, ewes were given single, aqueous, oral doses of saline (NaCl, 150 mg·kg of BW(-1)) or 150, 300, or 450 mg of NaClO(3)·kg(-1) of BW. At 24.0 ± 0.8 h after treatment, fecal samples were collected aseptically from the rectum of each ewe. For both experiments, generic E. coli were enumerated from intestinal contents and feces within 4 to 12 h after collection. In Exp. 1, the effect (P = 0.08) of NaClO(3) on the presence of generic E. coli in colon contents was dose-dependent. This effect was linear (P < 0.01) and negative, which indicated that as NaClO(3) dose increased, generic E. coli that could be isolated from colon contents decreased. Specifically, lambs dosed with 60 and 90 mg of NaClO(3)·kg(-1) of BW had fewer E. coli cfu·g(-1) of content than control lambs (P < 0.06). Lambs dosed with 90 mg of NaClO(3)·kg(-1) of BW had fewer E. coli cfu·g(-1) of content than lambs dosed with 30 mg of NaClO(3)·kg(-1) of BW (P = 0.09). Sodium chlorate dose did not influence (P = 0.58) the presence of generic E. coli in contents collected from the cecum. In Exp. 2, the effect (P < 0.0001) of NaClO(3) on the presence of E. coli in fecal contents from ewes was dose-dependent. This effect was quadratic (P < 0.0001) and negative; ewes dosed with 150, 300, and 450 mg of NaClO(3)·kg(-1) of BW had fewer E. coli cfu·g(-1) of feces than control ewes. No differences in E. coli cfu·g(-1) of feces were detected between NaClO(3) treatments (P = 0.88 to 0.97). Based on these results, a single oral dose of at least 60 and 150 mg of NaClO(3)·kg(-1) of BW in neonatal lambs and yearling ewes, respectively, significantly decreased the presence of generic E. coli in contents from the lower intestine.     

Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.     

Effect of spiramycin and tulathromycin on abomasal emptying rate in milk-fed calves

Impaired abomasal motility is common in cattle with abomasal disorders. The macrolide erythromycin has been demonstrated to be an effective prokinetic agent in healthy calves and in adult cattle with abomasal volvulus or left displaced abomasum. We hypothesized that 2 structurally related macrolides, spiramycin and tulathromycin, would also be effective prokinetic agents in cattle. Six milk-fed, male, Holstein-Friesian calves were administered each of the following 4 treatments: spiramycin, 75 000 IU/kg BW, IM, this dose approximates 25 mg/kg BW, IM; tulathromycin, 2.5 mg/kg BW, SC; 2 mL of 0.9% NaCl (negative control); and erythromycin, 8.8 mg/kg BW, IM (positive control). Calves were fed 2 L of cow’s milk containing acetaminophen (50 mg/kg body weight) 30 min after each treatment was administered and jugular venous blood samples were obtained periodically after the start of sucking. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration. Spiramycin, tulathromycin, and the positive control erythromycin increased abomasal emptying rate compared to the negative control. We conclude that the labeled antimicrobial dose of spiramycin and tulathromycin increases the abomasal emptying rate in healthy milk-fed calves. Additional studies investigating whether spiramycin and tulathromycin exert a prokinetic effect in adult cattle with abomasal hypomotility appear indicated.     

Elicitation of release of luteinizing hormone by N-methyl-d,l-aspartic acid during three paradigms of suppressed secretion of luteinizing hormone in the female pig.

Two experiments were conducted to determine the minimal effective dose during lactation and site of action of N-methyl-d,l-aspartic acid (NMA) for elicitation of release of luteinizing hormone (LH) in female pigs. In the first experiment, three doses of NMA were given to lactating primiparous sows in which endogenous LH was suppressed by suckling of litters. In the second experiment, ovariectomized gilts were pretreated with estradiol benzoate or porcine antisera against GnRH to suppress LH and then given NMA to determine if it elicited secretion of LH directly at the anterior pituitary or through release of GnRH. In experiment 1, 3 lactating sows (17 +/- 1.5 d postpartum) were each given three doses of NMA (1.5, 3.0 and 5.0 mg/kg body weight [BW]; IV) on 3 consecutive days in a Latin Square design. Blood samples were collected every 10 min from -1 to 1 hr from injection of NMA. NMA at 1.5 and 3.0 mg/kg did not affect (p greater than .5) secretion of LH; however, 5 mg NMA/kg elicited a 114% increase (p less than .001) in circulating levels of LH during 1 hr after treatment. In experiment 2, 8 ovariectomized gilts were given either estradiol benzoate (EB; 10 micrograms/kg BW; IM n = 4) to suppress release of GnRH or porcine antiserum against GnRH (GnRH-Ab; titer 1:8,000; 1 ml/kg BW; IV; n = 4) to neutralize endogenous GnRH. Gilts infused with GnRH-Ab were given a second dose of antiserum 24 hr after the first. Gilts were then given NMA (10 mg/kg BW; IV) 33 hr after EB or initial GnRH-Ab. Blood samples were drawn every 6 hr from -12 to 24 hr from EB or GnRH-Ab treatments, and every 10 min from -2 to 2 hr from NMA. Serum LH declined (p less than .001) after EB (from 1.87 +/- .2 ng/ml at 12 hr before EB to 0.46 +/- .02 ng/ml during 24 hr after EB) and GnRH-Ab (from 1.97 +/- .1 to 0.59 +/- .02 ng/ml). In gilts treated with EB, the area under the curve (AUC) for the LH response (ng.ml-1.min) 1 hr after NMA (38.7 +/- 3) was significantly greater (p less than .01) than the 1 hr prior to NMA (21.3 +/- 1.5). Treatment with NMA had no effect (p greater than .5) on secretion of LH in gilts infused with GnRH-Ab.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of serum folates of preruminant and ruminant calves to a dietary supplement of folic acid.

The effect of dietary supplemental folic acid on serum folates of preruminant and ruminant calves was studied. In Trial 1, doses of 0, .07, .14, .28, and .56 mg of folic acid per kilogram of BW were added to the milk of preruminant calves. In Trial 2, doses of 0, .5, 1, 2, and 4 mg of folic acid per kilogram of BW were incorporated into the concentrates of ruminant heifers. In the first part of each trial, serum folates were determined in blood samples taken 0, 1, 2, 4, 8, 16 (both trials), and 32 h (Trial 2) after a single meal supplemented with folic acid. In the second part of the two trials, the supplement of folic acid was given in feed during seven consecutive days. Blood samples were taken the day before the trial and subsequently every day during 7 d. In preruminant and ruminant calves, the area under the curve and the peak of concentration of serum folates after a meal increased with the dose ingested (P less than or equal to .05, linear and quadratic effect of doses, respectively) but the amount of folic acid needed to obtain a similar response was lower for preruminant than for ruminant calves. In preruminants, the time to reach the maximal concentration was 3 to 4 h after the meal, whatever the dose ingested (P less than or equal to .05), whereas in ruminants this time decreased with the dose ingested (quadratic effect of treatment, P less than or equal to .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in cats

OBJECTIVE: To compare cardiovascular effects of equipotent infusion doses of propofol alone and in combination with ketamine administered with and without noxious stimulation in cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with propofol (loading dose, 6.6 mg/kg; constant rate infusion [CRI], 0.22 mg/kg/min) and instrumented for blood collection and measurement of blood pressures and cardiac output. Cats were maintained at this CRI for a further 60 minutes, and blood samples and measurements were taken. A noxious stimulus was applied for 5 minutes, and blood samples and measurements were obtained. Propofol concentration was decreased to 0.14 mg/kg/min, and ketamine (loading dose, 2 mg/kg; CRI, 23 microg/kg/min) was administered. After a further 60 minutes, blood samples and measurements were taken. A second 5-minute noxious stimulus was applied, and blood samples and measurements were obtained. RESULTS: Mean arterial pressure, central venous pressure, pulmonary arterial occlusion pressure, stroke index, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, partial pressure of oxygen in mixed venous blood, pH of arterial blood, PaCO2, arterial bicarbonate concentration, and base deficit values collected during propofol were not changed by the addition of ketamine and reduction of propofol. Compared with propofol, ketamine and reduction of propofol significantly increased mean pulmonary arterial pressure and venous admixture and significantly decreased PaO2. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of propofol by CRI for maintenance of anesthesia induced stable hemodynamics and could prove to be clinically useful in cats.