This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO2) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO2) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO2 to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO2 and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species.

The objective of this study was to determine whether post-vaccination antibody titers vary according to body weight in adult dogs. Antibody titers against canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine adenovirus type 1 (CAdV-1) were measured for 978 domestic adult dogs from 2 to 6 y of age. The dogs had been vaccinated approximately 12 mo earlier with a commercial combination vaccine. The dogs were divided into groups according to their weight. It was found that mean antibody titers in all weight groups were sufficient to prevent infection. Intergroup comparison, however, revealed that CPV-2 antibody titers were significantly higher in the Super Light (< 5 kg) group than in the Medium (10 to 19.9 kg) and Heavy (> 20 kg) groups and were also significantly higher in the Light (5 to 9.9 kg) group than in the Heavy group. Antibody titers against CDV were significantly higher in the Super Light, Light, and Medium groups than in the Heavy group. There were no significant differences among the groups for the CAdV-1 antibody titers.

Objective-To evaluate cross protection provided by administration of contagious ecthyma vaccines against strains of orf virus in goats. Animals-126 Boer-Spanish crossbred goats (3 to 20 days old). Procedures-85 goats were vaccinated with a goat-derived contagious ecthyma vaccine. Of these, 41 were challenge exposed with the virus strain for the contagious ecthyma vaccine, 40 were challenge exposed with a more virulent field strain of orf virus, and 4 were lost to predation or died. Another 41 goats were vaccinated with a vaccine produced from a more virulent field strain of orf virus; of these, 18 were challenge exposed with the virus strain of the goat-derived contagious ecthyma vaccine, 18 were challenge exposed with the more virulent field strain of orf virus, and 5 were lost to predation or died. Results-Vaccination with the goat-derived contagious ecthyma vaccine did not significantly reduce the number of goats with lesions or lesion severity caused by challenge exposure with the more virulent field strain of orf virus. Vaccination with the vaccine produced from the more virulent field strain of orf virus significantly reduced the number of goats with lesions attributable to challenge exposure with the virus strain of the goat-derived contagious ecthyma vaccine, but it failed to significantly reduce lesion severity. Conclusions and Clinical Relevance-Vaccination did not result in cross protection for the 2 strains of orf virus. This may have been attributable to antigenic differences and may be a factor in outbreaks of contagious ecthyma in vaccinated goats.

Objective: To determine the effects of exercise on the distribution and pharmacokinetics of technetium Tc 99m medronate (99mTc-MDP) following intra-articular (IA) injection in horses. Animals: 5 horses. Procedures: 1 antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5), and the contralateral ACJ was evaluated in the nonexercised group (5) after a minimum washout period of 7 days. Following IA injection of 99mTc-MDP (148 MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma and scintigraphic radioactivity were determined over time, and pharmacokinetic parameters were generated via noncompartmental and compartmental analyses. Each horse was monitored via physical and lameness examination and ACJ synovial fluid analysis before injection and at days 1, 2, 3, and 7. Results: Lameness was not observed. Mean ± SD synovial fluid WBC count increased at day 1 (exercised, 721 ± 234 cells/μL; nonexercised, 948 ± 223 cells/μL), but returned to baseline at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the exercised group (16.00 ± 2.35 minutes) than the nonexercised group (43.75 ± 3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves revealed a greater negative slope in the exercised group within the first 25 minutes. There was no difference in absorption or elimination rate constants in a 2-compartment model. Conclusions and Clinical Relevance: IA injection of 99mTc-MDP was safe and effective for evaluating synovial solute distribution. Exercise significantly increased early transfer of 99mTc-MDP from the ACJ into plasma, although absorption and elimination rate constants were not affected. Exercise may affect synovial clearance and withdrawal times of medications administered IA.

Objective: To determine whether the extent of disease in dogs with lymphoma can be assessed via flow cytometry and to evaluate the suitability of fine-needle aspirates from the liver and spleen of dogs for flow cytometric examination. Animals: 44 dogs with multicentric B-cell (n = 35) or T-cell lymphoma (9) and 5 healthy control dogs. Procedures: Peripheral blood and bone marrow samples and fine-needle aspirates of lymph node, liver, and spleen were examined via flow cytometry. Logarithmically transformed T-cell–to–B-cell percentage ratio (log[T:B]) values were calculated. Thresholds defined by use of log(T:B) values of samples from control dogs were used to determine extranodal lymphoma involvement in lymphoma-affected dogs; results were compared with cytologic findings. Results: 12 of 245 (5%) samples (9 liver, 1 spleen, and 2 bone marrow) had insufficient cellularity for flow cytometric evaluation. Mean log(T:B) values of samples from dogs with B-cell lymphoma were significantly lower than those of samples from the same site in dogs with T-cell lymphoma and in control dogs. In dogs with T-cell lymphoma, the log(T:B) of lymph node, bone marrow, and spleen samples was significantly higher than in control dogs. Of 165 samples assessed for extranodal lymphoma involvement, 116 (70%) tested positive via flow cytometric analysis; results agreed with cytologic findings in 133 of 161 (83%) samples evaluated via both methods. Conclusions and Clinical Relevance: Results suggested that flow cytometry may aid in detection of extranodal lymphoma involvement in dogs, but further research is needed. Most fine-needle aspirates of liver and spleen were suitable for flow cytometric evaluation.

Objective: To determine whether feeding-induced activation of translation initiation factors, specifically protein kinase B, ribosomal protein S6 kinase (S6K1), ribosomal protein S6 (rpS6), and eukaryotic initiation factor 4E binding protein 1, in horses is affected by age. Animals: 6 yearlings, six 2-year-old horses, and 6 mature horses. Procedures: After an 18-hour period of feed withholding, horses consumed a high-protein meal (2 g/kg) at time 0 and 30 minutes (postprandial state) or continued to have feed withheld (postabsorptive state). Blood samples were collected for the duration of the experimental procedures and used to determine plasma concentrations of glucose, insulin, and amino acids. At 90 minutes, biopsy specimens were collected from a gluteal muscle and used to measure phosphorylation of translation initiation factors. Results: Plasma glucose, insulin, and amino acid concentrations were elevated for the postprandial state, compared with results for the postabsorptive state, regardless of age. Phosphorylation of protein kinase B, S6K1, rpS6, and eukaryotic initation factor 4E binding protein 1 was increased for the postprandial state. There was an effect of age with increased phosphorylation of S6K1 at Thr389 and rpS6 at Ser235/236 in the yearlings and mature horses, compared with results for the 2-year-old horses. Conclusions and Clinical Relevance: Food consumption resulted in an increase in the activation of translation initiation factors, with the highest degree of responsiveness in the yearlings. This indicated that increased muscle accretion seen during growth could be a result of increased rates of muscle protein synthesis in response to a meal stimulus.

Objective: To determine expression of microRNA (miRNA) in urinary bladder samples obtained from dogs with grossly normal urinary bladders, inflammatory bladder disease, or transitional cell carcinoma (TCC) and in cells of established canine TCC cell lines. Sample: Samples of grossly normal bladders (n = 4) and bladders from dogs with inflammatory bladder disease (13) or TCC (18), and cells of 5 established canine TCC cell lines. Procedures: Expression of 5 miRNAs (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) that target p53, Rb, or Bcl-2 protein pathways was determined for bladder samples and cells via quantitative real-time PCR assay. Effects of cisplatin (5μM) on proliferation and miRNA expression of cells were determined. Results: Expression of miR-34a and miR-106b was significantly higher in TCC samples than it was in samples of grossly normal bladders. Expression of miR-34a, miR-16, miR-103b, and miR-106b was higher in TCC samples than it was in bladder samples from dogs with inflammatory bladder disease. Cells of established canine TCC cell lines that had the lowest growth after cisplatin treatment had increased miR-34a expression after such treatment. Conclusions and Clinical Relevance: Findings of this study indicated results of miRNA expression assays can be used to distinguish between samples of grossly normal bladders and bladders of dogs with inflammatory bladder disease or TCC. This finding may have clinical relevance because currently available diagnostic tests cannot be used to differentiate these tissues, and inflammatory bladder disease and TCC are both prevalent in dogs. Validation of miRNA expression assays as diagnostic tests may be warranted.

Objective-To compare daily endogenous cortisol production rate and the pharmacokinetics of an IV bolus of hydrocortisone between neonatal foals and adult horses. Animals-10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses. Procedures-Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered IV to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid IV bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals. Results-The mean +/- SD 24-hour cortisol concentration was significantly lower in foals (20 +/- 4 ng/mL) than in horses (26 +/- 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 +/- 320 ng/kg/d) than in horses (2,140 +/- 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 +/- 1.11 L/kg) and total body clearance (1.39 +/- 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 +/- 343 ng/mL) than did horses (0.58 +/- 0.15 L/kg, 0.349 +/- 0.065 L/kg/h, and 8,934 +/- 3,843 ng/mL, respectively). Conclusions and Clinical Relevance-Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.

Objective: To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses. Animals: 10 client-owned horses with IMMK. Procedures: Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained). Equine IgG, IgM, and IgA antibodies were used to detect corneal immunoglobulin via direct immunofluorescence (10 eyes). Serum and aqueous humor (AH) samples from 3 horses with IMMK were used to detect circulating and intraocular IgG against corneal antigens via indirect immunofluorescence on unaffected equine cornea. Results: Percentage scores (scale, 0 to 4) of cells expressing CD3 (median, 2.35 [range, 0.2 to 3.7]; mean ± SD, 2.36 ± 1.08) were significantly greater than scores of cells expressing CD79a (median, 0.55 [range, 0 to 1.5]; mean, 0.69 ± 0.72). All samples stained positively for CD4- and CD8-expressing cells, with no significant difference in scoring. All samples stained positively for IgG, IgM, and IgA. No serum or AH samples collected from horses with IMMK reacted with unaffected equine cornea. Conclusions and Clinical Relevance: Pathogenesis of superficial stromal IMMK included cell-mediated inflammation governed by both cytotoxic and helper T cells. Local immunoglobulins were present in affected corneas; however, corneal-binding immunoglobulins were not detected in the serum or AH from horses with IMMK.

Objective: To determine whether withholding of food affects autonomic nervous system balance by analysis of heart rate (HR), HR variability (HRV), and frequency of second-degree atrioventricular block in horses. Animals: 5 healthy Thoroughbreds. Procedures: For two 24-hour periods in a crossover study, food was withheld from horses or horses were maintained on their regular feeding schedule (control conditions) in their stalls and Holter monitor ECG recordings were obtained. The ECGs were analyzed by use of fast-Fourier transformation, and power spectrum densities were calculated for low-frequency (0.01 to 0.07 Hz) and high-frequency (0.07 to 0.6 Hz) variations in HR. Serum cortisol and plasma ACTH, norepinephrine, and glucose concentrations were measured at predetermined time points. Results: Withholding of food resulted in significantly lower HR and more frequent second-degree atrioventricular block (the frequency of which was inversely related to the HR), compared with findings for control conditions. Circadian rhythms were similar during food-withholding and control conditions; peak HR was detected from 7:00 pm to 8:00 pm, and the lowest HR was detected in the early morning. During food-withholding conditions, the low-frequency and high-frequency components of HRV were significantly higher, and the low-frequency-to-high-frequency ratio was lower than during control conditions. Serum cortisol concentration was higher and plasma glucose concentration was lower at 6:00 pm in horses when food was withheld, compared with findings during control conditions. Conclusions and Clinical Relevance: Indices of HRV seemed to be sensitive to changes in autonomic nervous activity and may be useful as clinical indices of the neuroendocrine response to stressors in horses.