Objective: To identify a subantimicrobial dose of doxycycline hyclate (SDD) and for the treatment of periodontitis in dogs. Animals: 20 healthy Beagles for measurement of serum doxycycline concentration and 15 Beagles with periodontitis for evaluation of the efficacy of the SDD. Procedures: 5 dogs each received doxycycline hyclate PO at a dose of 1, 2, 3, or 5 mg/kg. Blood samples were collected before and after administration, and serum concentrations of doxycycline were measured via high-performance liquid chromatography. Mean serum doxycycline concentrations were calculated, and SDDs were identified. In a separate trial, the identified SDDs (1 or 2 mg/kg) were administered PO once a day for 1 month to dogs with periodontitis (n = 5/group) and a control group (5) was fed vehicle only during the same period. Degree of gingival attachment and bleeding on probing (present or absent) were recorded. Gingival samples were collected before and after the 1-month period from the same anatomic sites. Degree of matrix metalloproteinase inhibition in gingival samples was determined via gelatin zymography and compared among treatment groups. Results: Mean serum doxycycline concentrations in healthy dogs that received 1 or 2 mg of doxycycline/kg were consistently significantly lower than the minimal inhibitory doxycycline concentration for treatment of periodontitis throughout the 24-hour posttreatment period. Zymographic intensities were lower in dogs given 1 and 2 mg/kg than in the control dogs, and the degree of gingival attachment and bleeding significantly improved in dogs given 2 mg/kg, compared with in the control dogs and dogs given 1 mg of doxycycline/kg. Conclusions and Clinical Relevance: A doxycycline dosage of 2 mg/kg daily appeared to be an appropriate subantimicrobial regimen for dogs with periodontitis. Furthermore, this dosage may be suitable for long-term treatment of gelatinolytic inflammatory diseases such as periodontitis in this species.

Objective: To compare quantitative magnetic resonance (QMR), dual-energy x-ray absorptiometry (DXA), and deuterium oxide (D2O) dilution methods for measurement of total body water (TBW), lean body mass (LBM), and fat mass (FM) in healthy cats and to assess QMR precision and accuracy. Animals: Domestic shorthair cats (58 and 32 cats for trials 1 and 2, respectively). Procedures: QMR scans of awake cats performed with 2 units were followed by administration of D2O tracer (100 mg/kg, PO). Cats then were anesthetized, which was followed by QMR and DXA scans. Jugular blood samples were collected before and 120 minutes after D2O administration. Results: QMR precision was similar between units (coefficient of variation < 2.9% for all measures). Fat mass, LBM, and TBW were similar for awake or sedated cats and differed by 4.0%, 3.4%, and 3.9%, respectively, depending on the unit. The QMR minimally underestimated TBW (1.4%) and LBM (4.4%) but significantly underestimated FM (29%), whereas DXA significantly underestimated LBM (9.2%) and quantitatively underestimated FM (9.3%). A significant relationship with D2O measurement was detected for all QMR (r2 > 0.84) and DXA (r2 > 0.84) measurements. Conclusions and Clinical Relevance: QMR was useful for determining body composition in cats; precision was improved over DXA. Quantitative magnetic resonance can be used to safely and rapidly acquire data without the need for anesthesia, facilitating frequent monitoring of weight changes in geriatric, extremely young, or ill pets. Compared with the D2O dilution method, QMR correction equations provided accurate data over a range of body compositions.

This study investigated the effects of 70% nitrous oxide (N(2)O) on the minimum alveolar concentration (MAC) of isoflurane (ISO) that prevents purposeful movement, the MAC of ISO at which there is no motor movement (MAC(NM)), and the MAC of ISO at which autonomic responses are blocked (MAC(BAR)) in dogs. Six adult, healthy, mixed-breed, intact male dogs were anesthetized with ISO delivered via mask. Baseline MAC, MAC(NM), and MACBAR of ISO were determined for each dog using a supra-maximal electrical stimulus (50 V, 50 Hz, 10 ms). Nitrous oxide (70%) was then administered and MAC and its derivatives (N(2)O-MAC, N(2)O-MAC(NM), and N(2)O-MAC(BAR)) were determined using the same methodology. The values for baseline MAC, MAC(NM), and MAC(BAR) were 1.39 ± 0.14, 1.59 ± 0.10, and 1.72 ± 0.16, respectively. The addition of 70% N(2)O decreased MAC, MAC(NM), and MAC(BAR) by 32%, 15%, and 25%, respectively.

Objective: To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production. Animals: 29 adult horses of various ages and breeds and either sex. Procedures: In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed for MMP-2 and MMP-9 activities via zymography. In part 2, horses received doxycycline (n = 5), oxytetracycline (5), flunixin meglumine (5), or pentoxifylline (4) before and for up to 12 hours after administration of LPS. Plasma was obtained and analyzed, and results were compared with results from the LPS-infused horses of part 1. Results: Administration of LPS significantly increased MMP-2 and MMP-9 activities in the venous circulation of horses. All MMP inhibitors significantly decreased LPS-induced increases in MMP activities but to differing degrees. Pentoxifylline and oxytetracycline appeared to be the most effective MMP-2 and MMP-9 inhibitors, whereas doxycycline and flunixin meglumine were more effective at inhibiting MMP-2 activity than MMP-9 activity. Conclusions and Clinical Relevance: IV administration of LPS to horses caused increased venous plasma activities of MMP-2 and MMP-9. These MMP activities were reduced by pentoxifylline and oxytetracycline, suggesting that further evaluation of these medications for treatment and prevention of MMP-associated diseases in horses is indicated.

Objective: To measure the effect of warm compress application on tissue temperature in healthy dogs. Animals: 10 healthy mixed-breed dogs. Procedures: Dogs were sedated with hydromorphone (0.1 mg/kg, IV) and diazepam (0.25 mg/kg, IV). Three 24-gauge thermocouple needles were inserted to a depth of 0.5 cm (superficial), 1.0 cm (middle), and 1.5 cm (deep) into a shaved, lumbar, epaxial region to measure tissue temperature. Warm (47°C) compresses were applied with gravity dependence for periods of 5, 10, and 20 minutes. Tissue temperature was recorded before compress application and at intervals for up to 80 minutes after application. Control data were collected while dogs received identical sedation but with no warm compress. Results: Mean temperature associated with 5 minutes of heat application at the superficial, middle, and deep depths was significantly increased, compared with the control temperature. Application for 10 minutes significantly increased the temperature at all depths, compared with 5 minutes of application. Mean temperature associated with 20 minutes of application was not different at the superficial or middle depths, compared with 10 minutes of application. Temperature at the deep depth associated with 10 minutes of application was significantly higher, compared with 20 minutes of application, but all temperature increases at this depth were minimal. Conclusions and Clinical Relevance: Results suggested that application of a warm compress should be performed for 10 minutes. Changes in temperature at a tissue depth of 1.5 cm were minimal or not detected. The optimal compress temperature to achieve therapeutic benefits was not determined.

Objective-To assess effects of in vitro meloxicam exposure on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis Sample-Femoral head cartilage from 16 dogs undergoing total hip replacement Procedures-Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG, chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1β, tumor necrosis factor-α, cyclooxygenase-1, cyclooxygenase-2, and nducible nitric oxide synthase gene expression were evaluated. Comparisons between tissues cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and 30.0 μg/mL for up to 30 days were performed by means of repeated-measures analysis. Results-Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA concentrations. Expression of ADAMTS-5 was significantly decreased in all groups on all days, compared with the day 0 value. On day 3, culture medium PGE2 concentrations were significantly lower in all meloxicam-treated groups, compared with values for controls, and values remained low. Culture medium MMP-3 concentrations were significantly lower on day 30 than on day 3 in all meloxicam-treated groups. Conclusions and Clinical Relevance-Results suggested that in vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days did not induce matrix degradation or stimulate MMP production. Meloxicam lowered PGE2 release from this tissue, and effects on tissue chondrocyte content and matrix composition were neutral.

Objective-To validate the use of a human enzyme immunoassay (EIA) kit for measurement of plasma antidiuretic hormone (ADH) concentration in dogs and evaluate plasma ADH concentrations in dogs with congestive heart failure (CHF) attributable to acquired cardiac disease, compared with findings in healthy dogs. Animals-6 healthy dogs and 12 dogs with CHF as a result of chronic degenerative valve disease or dilated cardiomyopathy. Procedures-Plasma samples from the 6 healthy dogs were pooled and used to validate the EIA kit for measurement of plasma ADH concentration in dogs by assessing intra-assay precision, dilutional linearity, and spiking recovery. Following validation, plasma ADH concentrations were measured in the 6 healthy dogs and in the 12 dogs with CHF for comparison. Results-The EIA kit measured ADH concentrations in canine plasma samples with acceptable intra-assay precision, dilutional linearity, and spiking recovery. The intra-assay coefficient of variation was 11%. By use of this assay, the median plasma concentration of ADH in dogs with CHF was 6.15 pg/mL (SD, 3.2 pg/mL; range, 4.18 to 15.47 pg/mL), which was significantly higher than the median concentration in healthy dogs (3.67 pg/mL [SD, 0.93 pg/mL; range, 3.49 to 5.45 pg/mL]). Conclusions and Clinical Relevance-Plasma ADH concentrations in dogs can be measured with the tested EIA kit. Plasma ADH concentrations were higher in dogs with CHF induced by acquired cardiac disease than in healthy dogs. This observation provides a basis for future studies evaluating circulating ADH concentrations in dogs with developing heart failure.

Lawsonia intracellularis infection causes proliferative enteropathy (PE) in many mammalian species, with porcine and equine proliferative enteropathy (PPE and EPE) known worldwide. Hamsters are a well-published animal model for PPE infection studies in pigs. There is no laboratory animal model for EPE infection studies and it is not known whether there is species-specificity for equine or porcine isolates of L. intracellularis in animal models. The objective of this study was to determine whether it is possible to generate typical EPE lesions in hamsters after inoculation with an equine strain of L. intracellularis (EPE strain) and whether it is comparatively possible to generate PPE lesions in rabbits after inoculation with a porcine strain of L. intracellularis (PPE strain). In 2 separate trials, 4-week-old and 3-week-old weanling golden Syrian hamsters were challenged with EPE strains and compared to uninfected (both trials) and PPE-infected controls (Trial 2 only). Concurrently, 6 female New Zealand white juvenile rabbits were infected with PPE strain and observed concomitantly to 8 similar rabbits infected with EPE strain for a different experiment. Hamsters and rabbits were observed for 21 to 24 days post-infection (DPI), depending on the experiment. Neither infected species developed clinical signs. The presence of disease was assessed with diagnostic techniques classically used for pigs and horses: immune-peroxidase monolayer assay on sera; quantitative polymerase chain reaction (qPCR) detection of molecular DNA in feces; and hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) on intestinal tissues. Our results showed that EPE-challenged hamsters do not develop infection when compared with PPE controls (IHC, P = 0.009; qPCR, P = 0.0003). Conversely, PPE-challenged rabbits do not develop typical intestinal lesions in comparison to EPE-challenged rabbits, with serological response at 14 DPI being significantly lower (P = 0.0023). In conclusion, PPE and EPE strains appear to have different host-specificities for hamsters and rabbits, respectively.

Objective—To determine the cardiopulmonary effects of 3 doses of isoflurane, with and without controlled mechanical ventilation and noxious stimulation, in healthy adult New Zealand white rabbits. Animals—6 adult female rabbits. Procedures—Each rabbit was administered isoflurane in oxygen at each of 3 anesthetic doses (1.0, 1.5, or 2.0 times the published minimum alveolar concentration of 2.07%). At each anesthetic dose, blood gas and cardiopulmonary measurements were obtained before and during application of a supramaximal noxious stimulus. Effects of spontaneous and mechanical ventilation were assessed during separate anesthetic episodes. Results—Mean ± SEM isoflurane concentrations used were 2.11 ± 0.04%, 3.14 ± 0.07%, and 4.15 ± 0.06%. During spontaneous ventilation, the rabbits’ Paco2 and mixed venous Pco2 significantly increased with concomitant reductions in both arterial and mixed venous pH as isoflurane concentration increased. Cardiac output and vascular resistance did not change significantly. Noxious stimulation minimally affected measured cardiopulmonary variables. During mechanical ventilation, significant reductions in arterial blood pressures and cardiac output occurred with increasing isoflurane dose. Systemic vascular resistance index at the highest anesthetic dose was significantly lower than the value at the lowest anesthetic dose. During noxious stimulation, systolic arterial blood pressure and cardiac output significantly increased at the 2 lower isoflurane concentrations, but not at the highest concentration. Conclusions and Clinical Relevance—In rabbits, isoflurane-induced dose-dependent cardiopulmonary depression was attributable to vasodilation and negative inotropy. At an isoflurane concentration of 4.15% with mechanical ventilation, cardiovascular depression was severe; use of unnecessarily high isoflurane concentrations in this species should be avoided.

Objective: To determine 2-deoxy-2-fluoro (fluorine 18)-d-glucose (18FDG) biodistribution in the coelom of bald eagles (Haliaeetus leucocephalus). Animals: 8 healthy adult bald eagles. Procedures: For each eagle, whole-body transmission noncontrast CT, 60-minute dynamic positron emission tomography (PET) of the celomic cavity (immediately after 18FDG injection), whole-body static PET 60 minutes after 18FDG injection, and whole-body contrast CT with iohexol were performed. After reconstruction, images were analyzed. Regions of interest were drawn over the ventricular myocardium, liver, spleen, proventriculus, cloaca, kidneys, and lungs on dynamic and static PET images. Standardized uptake values were calculated. Results: Kidneys had the most intense 18FDG uptake, followed by cloaca and intestinal tract; liver activity was mild and slightly more intense than that of the spleen; proventricular activity was always present, whereas little to no activity was identified in the wall of the ventriculus. Activity in the myocardium was present in all birds but varied in intensity among birds. The lungs had no visibly discernible activity. Mean ± SD standardized uptake values calculated with representative regions of interest at 60 minutes were as follows: myocardium, 1. 6 ± 0.2 (transverse plane) and 1.3 ± 0.3 (sagittal plane); liver, 1.1 ± 0.1; spleen, 0.9 ± 0.1; proventriculus, 1.0 ± 0.1; cloaca, 4.4 ± 2.7; right kidney, 17.3 ± 1.0; left kidney, 17.6 ± 0.3; and right and left lungs (each), 0.3 ± 0.02. Conclusions and Clinical Relevance: The study established the biodistribution of 18FDG in adult eagles, providing a baseline for clinical investigation and future research.