The effect of hypercapnia on the arrhythmogenic dose of epinephrine (ADE) was investigated in 14 horses. Anesthesia was induced with guaifenesin and thiamylal sodium and was maintained at an end-tidal halothane concentration between 0.86 and 0.92%. Base-apex ECG, cardiac output, and facial artery blood pressure were measured and recorded. The ADE was determined at normocapnia (arterial partial pressure of carbon dioxide [Pa(CO2)] = 35 to 45 mm of Hg), at hypercapnia (Pa(CO2) = 70 to 80 mm of Hg), and after return to normocapnia. Epinephrine was infused at arithmetically spaced increasing rates (initial rate = 0.25 micrograms/kg of body weight/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate, to the nearest 0.25 micrograms/kg/min, at which 4 premature ventricular complexes occurred in a 15-second period. The ADE (mean +/- SD) during hypercapnia (1.04 +/- 0.23 micrograms/kg/min) was significantly (P < 0.05) less than the ADE at normocapnia (1.35 +/- 0.38 micrograms/kg/min), whereas the ADE after return to normocapnia (1.17 +/- 0.22 micrograms/kg/min) was not significantly different from those during normocapnia or hypercapnia. Baseline systolic and diastolic arterial pressures and cardiac output decreased after return to normocapnia. Significant differences were not found in arterial partial pressure of O2 (Pa(O2)) or in base excess during the experiment. Two horses developed ventricular fibrillation and died during normocapnic determinations of ADE. Hypercapnia was associated with an increased risk of developing ventricular arrhythmias in horses anesthetized with guaifenesin, thiamylal sodium, and halothane.

Right atrial (RA), right ventricular (RV), pulmonary artery (PA), and pulmonary artery wedge (Paw) pressures were examined, using catheter-mounted micromanometers, in 8 healthy horses at rest and during galloping on a treadmill at belt speeds of 8, 10, and 13 m/s. The in vivo signals from the micromanometers were matched with those from conventional fluid-filled catheter transducers leveled at the scapulohumeral joint. Thirty minutes after completing control exercise measurements, furosemide was administered IV at a dosage of 1 mg/kg of body weight, and resting, as well as exercise, measurements were repeated 4 hours later. Studies also were performed on a separate day, when only postfurosemide resting and exercise data were collected. Prefurosemide and postfurosemide heart rate values for rest (37 +/- 2 beats/min, mean +/- SEM), as well as for exercise (213 +/- 5 beats/min at 13 m/s), were similar. Prefurosemide mean RA, PA, and PAW pressures were increased significantly (P < 0.05) from resting values of 8 +/-2, 31 +/- 2, and 18 +/- 2 mm of Hg, respectively, to 44 +/- 4, 89 +/- 5, and 56 +/- 4 mm of Hg with exercise at 13 m/s. Furosemide administration resulted in marked diuresis, and resting mean RA, PA, and PAW pressures decreased significantly (P < 0.05) to 1 +/-1, 27 +/- 2, and 11 +/- 2 mm of Hg, respectively, 4 hours after furosemide administration. Although pressures increased markedly with exercise (corresponding values being 31 +/- 5, 79 +/- 6, and 44 +/- 4 mm of Hg), these 4-hour postfurosemide exercise values were significantly (P < 0.05) less than those recorded with prefurosemide exertion. Intravascular pulmonary capillary pressure, calculated as the average of mean PA and PAW pressures, during prefurosemide exercise (73 +/- 5 mm of Hg) significantly (P < 0.05) exceeded that during exercise performed 4 hours after furosemide administration (61 +/- 5 mm of Hg). Attenuation by furosemide of the exercise-induced increase in pulmonary capillary pressure may have a role in limiting or reducing the extent of exercise-induced pulmonary hemorrhage in horses.

The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml mean, 880.2 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 +/- 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 +/- 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 +/- 0.598 ng-min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 +/- 0.308 ng-min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 +/- 2.55 ml/min/kg), compared with that on day 1 6.16 +/- 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital. Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital.

Sequential assessments of pancreatic structure and function were performed on a female German Shepherd Dog bred from parents with exocrine pancreatic insufficiency (EPI), to monitor development of pancreatic acinar atrophy in this breed. Determinations of serum trypsin-like immunoreactivity (TLI), results of N-benzoyl-L-tyrosyl-P-aminobenzoic acid test, fecal soy bean stimulation test (SST), and gross and histologic examinations of the pancreas did not provide evidence of exocrine pancreatic disease up to 13 months of age. However, electron microscopy revealed degenerative abnormalities of acinar cells that were already apparent at 6 weeks and became more extensive with age. Examination of the pancreas at 22 months of age also indicated no gross or histologic abnormalities, but electron microscopy revealed widespread degenerative changes, including dilatation of the rough endoplasmic reticulum and extensive fusion of zymogen granules affecting most of the acinar cells. Serum TLI concentration nm markedly reduced at that time, indicative of EPI, but the dog remained healthy and results of the SST were normal. Within 1 month, the dog had developed clinical signs of EPI, and not only serum Tli concentration, but also results of the N-benzoyl-L-tyrosyl-P-aminobenzoic acid test and SST were compatible with severe loss of exocrine pancreatic tissue. This loss was confirmed by gross and histologic examination of the pancreas at 25 months, which revealed typical features of pancreatic acinar atrophy, including scattered and disorganized exocrine cells in the small remnants of pancreatic tissue. These findings indicate that in German Shepherd Dogs, pancreatic acinar atrophy may involve interference with normal intracellular processing of

To investigate the feasibility of using changes in body or mammary temperature to detect mastitis, radiotransmitters were implanted midway between rear udder quarters and in the peritoneal cavity of 5 Holstein cows (1 to 3 months in lactation) housed in an environmental chamber (16 +/- 2 C; lights on 7:00 AM to 11:00 PM). After a 6-week control period, Escherichia coli endotoxin (0.5 mg) was injected after the morning milking into left rear teat cisterns via the teat canal. Wisconsin mastitis test score and somatic cell count in all quarters increased significantly (P < 0.01) by the next milking. Effects were greatest in the endotoxin-exposed quarters. Milk yields for all quarters decreased significantly (P < 0.01) by the first milking after endotoxin injection. Udder and body temperatures at milkings were similar and were not affected by treatment. When temperatures were averaged for the 5 cows for each of 120 time points/d, average temperatures, relative to time of injection of endotoxin, were increased by 0.5 C above baseline at 2.75 hours, peaked at + 2.9 C at 6.50 hours, and remained high through 9.25 hours after injection. Power spectra calculated for individual cows on a daily basis universally indicated an increase in power at low frequencies on the day of injection. Subsequently, Streptococcus agalactiae (200 colony-forming units) was injected into right rear teat cisterns. Wisconsin mastitis test score increased at the second milking after injection. Cell count and quarter milk yield decreased by the third milking. As with endotoxin, injection of S agalactiae could not be detected via a change in temperature at milkings. Of the 5 cows, 3 had a peak in temperature after injection of S agalactiae. Average temperatures for these 3 cows relative to time of injection, were increased by 0.5 C above baseline at 24.25 hours, peaked at + 1.4 C at 26.25 hours, and remained high through 28.75 hours after injection. Power spectra calculated for the day in which a temperature peak was detected for these 3 cows indicated an increase in power at low frequencies, compared with spectra for all other days. Similar increases in power were also detected for the 2 cows that did not have temperature peaks. When clinical signs of mastitis are obvious at milking, there is little advantage of using body temperature for detection of infection. When clinical signs are not obvious, body temperature is often only minimally increased. Thus, monitoring body temperature at milkings adds little to the ability to detect mastitis. Of more interest is the ability to detect transient temperature increases that often develop in association with less-severe infections. Also, as early treatment increases the likelihood of successful treatment, detection of the onset of temperature increases would be advantageous for treatment of severe infections. Detection of a transient temperature peak requires taking temperature readings every 2 hours. To detect mastitis when a temperature peak does not occur requires measurement every 15 minutes to calculate power spectra. The ability to detect the onset of acute clinical infections and subclinical infections, using frequent temperature readings, indicates that development of a practical radiotelemetry system for use on farms may be warranted, depending on cost. The added potential of using body temperature to monitor general health and to detect estrus enhances the economic feasibility of developing such a system.

Cytologic and bacteriologic responses, and changes in cytokine activity were evaluated in secretions of Staphylococcus aureus-infected mammary glands after treatment of heifers with recombinant bovine interferon gamma (rbIFN gamma) or interleukin 2 (rbIL-2). Two groups of 4 heifers each, experimentally infected with 10(7) colony-forming units (CFU) of S aureus, were injected in 2 quarters via the teat canal, with 10(5) U of rbIFN gamma (trial 1) or 7.5 X 10(5) U of rbIL-2 (trial 2) 2 weeks after experimentally induced infection; control quarters received phosphate-buffered saline solution. Mammary secretion samples were taken on days 0, 1, 2, 3, 4, 7, and 14 after cytokine infusion. Secretions were diluted 1:10 and used to perform somatic cell counts (SCC), differential cell counts, and CFU enumerations, and to determine the number of leukocytes expressing major histocompatibility complex class-II (MHC II) antigens. In addition, mammary secretion samples taken on days 0, 1, and 2 were processed to obtain skimmed milk for evaluation of rbIFN gamma- and rbIL-2-like activities. Treatment with rbIFN gamma did not influence SCC, or differential or bacteria counts, or the number of leukocytes expressing MHC II antigens. However, rbIL-2 stimulated leukocytosis, which may have reduced bacteria counts early in the trial; treatment with this cytokine also increased the neutrophil, macrophage, lymphocyte, and eosinophil counts in secretions. Similarly, numbers of MHC II-positive leukocytes were greater in rbIL-2-treated quarters vs controls. Compared with day 0, IFN gamma-like activity was increased on only day 1 in both trials. Interleukin-2-like activity was not influenced in the rbIFN gamma trial, but was increased on days 1 and 2 in the rbIL-2 trials. Results indicated that neither cytokine may have had a major influence on the course of established S aureus infections. However, the increased SCC in rbIL-2-treated quarters may have accounted for the reduction in CFU throughout the trial after treatment with this cytokine. Greatest cytokine-like activity was observed on day 1; however, the consequences of cytokine activity, such as the sustained eosinophilia after rbIL-2 treatment, were detected over the 14-day trial period, indicating possible prolonged action.

One hundred two dogs without known gastric lesions were evaluated to establish a reference range of gastric rugal fold thickness (millimeters). Mucosal folds were measureable for 63 examinations, and the length of the second lumbar vertebra was measured for 61 of the 63 (centimeters). Body weight was available in the case records of 29 dogs. Measurements of the mucosal folds were related to body weight (n = 29) and length of the second lumbar vertebra (n = 61) by use of linear regression analysis. Reference range of normal gastric mucosal fold thickness, 1 to 8 mm, was defined by this study for dogs of any breed weighing between 2 and 50 kg.

Reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free sheep (Cheviot and Suffolk breeds) to measure scrapie transmission via the embryo (using offspring from embryos of scrapie-inoculated donors and scrapie-free recipients) and via the uterus (using offspring from embryos of scrapie-free donors and scrapie-inoculated recipients taken by cesarean section). Two control groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie-inoculated parents (positive), also were included. All sheep were observed for clinical signs of scrapie until death or for a minimum of 60 months. Final diagnosis was made on the basis of histopathologic findings or results of mouse inoculation and/or proteinase-K-resistant protein analysis. Thirty to 61% of the scrapie-inoculated donor/recipient sheep within groups developed scrapie within 8 to 44 months after inoculation. None of the scrapie-free donor/recipients, including those gestating embryos from scrapie-inoculated donors, developed scrapie. Also, none of the offspring observed to larger than or equal to 24 months of age from reciprocal cross, via embryo (0/67), or via the uterus (0/25), or from the negative-control group (0/33) developed scrapie. Fifty-six of the offspring via embryo, 19 of these via the uterus, and 31 negative controls survived to larger than or equal to 60 months of age. Of the 21 sheep in the positive-control group, 2 (9.5%) developed scrapie, 1 at 31 months of age and 1 at 42 months of age. In the Cheviot offspring, the percentage of sheep carrying the short incubation allele ranged from 24 to 44% and the percentage in the Suffolk offspring ranged from 61 to 83%. These proportions indicate high degree of susceptibility to the disease. Results indicate that under the conditions of these experiments, scrapie was not transmitted to the offspring via the embryo or the uterus.

Brain capillary function was assessed in 4- to 6-week-old calves given lead acetate (15 mg/kg of body weight) orally for 7 to 8 days. Neurologic signs of lead poisoning included CNS depression, blindness, and hyperesthesia. Brain capillaries were isolated from cerebral cortex of control and lead-treated calves and evaluated for metabolic indicators, ion transport, and prolyl hydroxylase activity. In lead-treated calves, the rate of glucose metabolism was less than half that in controls. Ion efflux of 45Ca or 36Cl from endothelial cell suspensions was not affected by lead treatment. Prolyl hydroxylase activity in endothelium and proline-to-hydroxyproline ratio in endothelial basement membranes were similar in control and lead-poisoned calves. Results indicate that lead may inhibit energy metabolism, but not ion transport or collagen biosynthesis in brain capillaries of calves and, compared with suckling rats, damage to the blood-brain barrier is less important. In calves, neuronal tissue may be the primary target for the CNS effects of lead.

Although feline immunodeficiency virus (FIV) and the unrelated retrovirus feline leukemia virus (FeLV) are associated with acquired immune deficiency in cats, experimental and field evidence indicates that coinfection with both viruses may lead to more serious disease syndrome. A third feline retrovirus, feline syncytium-forming virus (FeSFV), which is far more prevalent than either FIV or FeLV and is considered nonpathogenic in nature, is consistently coisolated from sick, FIV-infected cats. To determine the potential role of FeSFV in enhancement of FIV-mediated disease, persistent FeSFV infection was established in 14 of 24 nine-month-old cats. Four months later, half the FeSFV-infected and half the noninfected cats were inoculated with blood obtained from a cat persistently infected with the Petaluma strain of FIV. At postinoculation week 17, 1 male cat infected with only FIV died of bacterial bronchopneumonia that could have been attributed to FIV-induced acquired immune deficiency-like syndrome. However, none of the remaining cats had clinical illness, whether infected with either virus alone or coinfected with both viruses. As early as postinoculation week 6, decreases were observed in the CD4+ to CD8+ T-lymphocyte ratio of both groups of cats inoculated with FIV. Infection with FeSFV had no effect on the CD4, to CD8+ T-cell ratio. Mitogen stimulation assays and total WBC count were unaffected by FeSFV infection, although an increase in numbers of neutrophils from FeSFV-infected cats was consistent, especially when compared with the decrease observed after FIV infection. Overall, results of the study indicate that coinfection with FeSFV may not enhance progression of the FIV-induced early stages of disease and that the positive correlation between FeSFV and FIV-induced acquired immune deficiency-like syndrome is attributable to a common mode of transmission, rather than to a synergistic effect of coinfection.