Healthy Beagle Dogs Research Articles

Basal glucose excretion in dogs: The impact of feeding, obesity, sex, and age.

BackgroundThe urine glucose (UG) measurements are an integral part of urinalyses, especially in dogs with polyuria and polydipsia. A positive dipstick result is considered pathologic for disease. This paradigm has been challenged by new ultrasensitive tests, where the manufacturers recommend tolerating slightly positive results. It implies that, as in other species, basal urine glucose losses can exceed the lower limits of detection using ultrasensitive glucose dipsticks in healthy dogs.ObjectivesWe aimed to determine whether glucose is routinely detectable using a sensitive quantitative wet chemistry method in the urine of nondiabetic, nonazotemic dogs, and investigate the impact of food intake, obesity, sex, castration status, and age.MethodsSerial UG measurements were performed in healthy clinic‐owned Beagle dogs that were randomly fasted or fed. Glucose was measured in morning urine samples from normal‐weight healthy and obese dogs, and the university's electronic database was searched for quantitative UG measurements (Gluco‐quant Enzyme Kit/Roche Diagnostics).ResultsSmall amounts of glucose were detected in 555 (99.1%) of 560 urine samples analyzed. All urine samples from the clinic‐owned Beagle dogs, as well as from privately owned obese and normal‐weight healthy dogs that tested positive for glucose. The median (range) UG concentration obtained from the university's electronic database was 0.39 (0‐1.55) mmol/L, and 2.2% of the samples tested negative. Feeding, obesity, gender, castration status, and age did not affect UG concentrations.ConclusionsStudies, including a larger number of healthy dogs, are warranted to define a cut‐off between physiologic and pathologic glucosuria.

Safety studies and viral shedding of intramuscular administration of oncolytic vaccinia virus TG6002 in healthy beagle dogs

BackgroundCancer is a leading cause of mortality for both humans and dogs. As spontaneous canine cancers appear to be relevant models of human cancers, developing new therapeutic approaches could benefit both species. Oncolytic virotherapy is a promising therapeutic approach in cancer treatment. TG6002 is a recombinant oncolytic vaccinia virus deleted in the thymidine kinase and ribonucleotide reductase genes and armed with the suicide gene FCU1 that encodes a protein which catalyses the conversion of the non-toxic 5-fluorocytosine into the toxic metabolite 5-fluorouracil. Previous studies have shown the ability of TG6002 to infect and replicate in canine tumor cell lines, and demonstrated its oncolytic potency in cell lines, xenograft models and canine mammary adenocarcinoma explants. Moreover, 5-fluorouracil synthesis has been confirmed in fresh canine mammary adenocarcinoma explants infected with TG6002 with 5-fluorocytosine. This study aims at assessing the safety profile and viral shedding after unique or repeated intramuscular injections of TG6002 in seven healthy Beagle dogs.ResultsRepeated intramuscular administrations of TG6002 at the dose of 5 × 107 PFU/kg resulted in no clinical or biological adverse effects. Residual TG6002 in blood, saliva, urine and feces of treated dogs was not detected by infectious titer assay nor by qPCR, ensuring the safety of the virus in the dogs and their environment.ConclusionsThese results establish the good tolerability of TG6002 in healthy dogs with undetectable viral shedding after multiple injections. This study supports the initiation of further studies in canine cancer patients to evaluate the oncolytic potential of TG6002 and provides critical data for clinical development of TG6002 as a human cancer therapy.

Simultaneous UPLC-MS/MS Determination of 6-mercaptopurine, 6-methylmercaptopurine and 6-thioguanine in Plasma: Application to the Pharmacokinetic Evaluation of Novel Dosage forms in Beagle Dogs

6-Mercaptopurine (6-MP) is widely used to treat pediatric acute lymphoblastic leukemia (ALL). Mini-tablets of 5 mg per tablet were developed for precision individual therapy for children and individuals with poor thiopurine S-methyltransferase (TPMT) or nucleoside diphophate-linked moiety X-type motif 15 (NUDT15) metabolism. This study investigated the pharmacokinetic profiles of mini-tablets and conventional tablets with an improved ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. After giving 8 healthy beagle dogs 50 mg 6-MP in different dosage forms, plasma samples collected at different time points were analyzed for pharmacokinetic evaluation. The samples were precipitated by methanol with 0.05% formic acid and separated on a Waters Atlantis T3 column (2.1 × 150 mm, 3 μm particles) using 0.1% formic acid in water and methanol at a flow rate of 0.4 mL/min in 4 min. This method showed good linearity, accuracy, precision and stability with a detection range of 5.0-500.0 ng/mL for 6-MP, 6-methylmercaptopurine (6-MMP) and 6-thioguanine (6-TG). The main parameters, half-life of apparent terminal disposition, maximum observed plasma concentration, total AUC extrapolated to infinity, AUC since initiation of the experiment, mean residence time, distribution volume and clearance were 1.62 ± 0.87 hours, 90.58 ± 60.43 ng/mL, 151.20 ± 94.18 ng·h/mL, 292.06 ± 184.02 ng·h2/mL, 1.90 ± 0.92 hours, 864.08 ± 538.52 L, and 432.75 ± 360.64 L/h for conventional tablets and 1.70 ± 1.10 hours, 84.15 ± 39.50 ng/mL, 147.70 ± 51.80 ng·h/mL, 300.92 ± 124.48 ng·h2/mL, 2.07 ± 0.50 hours, 756.90 ± 324.00 L, and 340.75 ± 125.81 L/h for minitablets, respectively. Paired t-tests showed no significant difference in any of the evaluated pharmacokinetic parameters between the two types tablets (P > 0.05). Two dosage forms showed the same pharmacokinetic characteristics. This developing, novel formulation will help to provide a more accurate and optimal dosing regimen of 6-MP for humans in the future.

Assessing the Safety, Tolerability, Pharmacokinetics, and Biodistribution of Novel Oral Formulations of Amphotericin B following Single- and Multiple-Dose Administration to Beagle Dogs.

The purpose of this study was to assess the safety, tolerability, pharmacokinetics (PK), and biodistribution of novel oral amphotericin B (AmpB) formulations following single- and multiple-oral-dose administration to healthy beagle dogs. The liquid formulation of AmpB was administered to three male dogs, and the capsule formulations of AmpB were administered to each of two groups of six male dogs. Blood was collected for pharmacokinetic evaluation on days 1, 2, and 3 (up to 72 h postdosing). Dogs receiving the capsule formulations further received a single oral dose of 100 mg once daily for three more days, and on the 4th day, blood samples were taken at 24 h postdosing and the dogs were humanely sacrificed with the removal of organs, from which tissue samples were taken for analysis of the AmpB content. Multiple-dose studies were completed for 7 or 14 days with daily doses of up to 1,000 mg/day with the capsule formulations. All oral formulations of AmpB following both single- and multiple-dose administration were well tolerated in the dogs, and there were no relevant adverse signs observed, such as changes in hematologic, coagulation, or biochemistry parameters; loss of weight; changes in food or water intake; or signs of gastrointestinal distress. The oral absorption of AmpB from the liquid formulation and the capsule formulations were similar, with no significant differences. The tissue distributions of AmpB were similar following repeated doses of the two capsule formulations to dogs. Following 14 days of treatment with the iCo-010 liquid formulation and the iCo-019 and iCo-022 capsule formulations, the range of values of the maximum observed plasma concentration (Cmax) was 53.2 to 62.3, 24.9 to 66.4, and 36.7 to 85.2 ng/ml, respectively; the range of values of the time to Cmax was 4 to 12, 4 to 24, and 2 to 24 h, respectively; and the range of values of the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration was 2,635 to 3,071, 1,053 to 2,517, and 1,443 to 3,713 ng · h/ml, respectively. We have developed a safe novel oral AmpB formulation suitable for future efficacy studies.

Investigations on Metabolic Changes in Beagle Dogs Fed Probiotic Queso Blanco Cheese and Identification of Candidate Probiotic Fecal Biomarkers Using Metabolomics Approaches.

Intake of probiotic cheese improves the intestinal health of humans and animals. However, metabolic changes in the intestines of dogs in response to the ingestion of probiotic cheese have not been evaluated. Thus, we aimed to determine the metabolic changes in healthy beagle dogs fed queso blanco cheese with added Lactobacillus reuteri KACC 92293 and Bifidobacterium longum KACC 91563 (QCLB) and to identify potential fecal biomarkers to distinguish the metabolic changes based on intake of probiotic cheese through metabolomics approaches. The dogs were randomly divided into three groups and fed a regular diet without any cheese (control), a diet with queso blanco cheese (QC), or one with QCLB for eight weeks. The concentrations of acetic, propionic, and 4-aminobutyric acids were increased in the QCLB group compared to those in the control group. Additionally, higher levels of propionic acid and lower levels of xylose were found in the QCLB group compared to those in the QC group. This is the first report on the identification of metabolic changes in beagle dogs fed queso blanco cheese with added L. reuteri KACC 92293 and B. longum KACC 91563. We also found that metabolomics approaches can be useful for identifying potential fecal markers in dogs fed probiotic cheese.

Efficacy and safety of bimatoprost 0.01% formulated in tight junction modulation technology compared to marketed benzalkonium chloride preserved bimatoprost 0.01% ophthalmic solution in healthy beagle dogs

Background: This study was undertaken to compare the efficacy and safety of the new technology tight junction modulation (TJM) bimatoprost 0.01% (TJM-bimatoprost), containing polyhexamethylene biguanide hydrochloride as a preservative, and marketed bimatoprost 0.01% (BKC-bimatoprost) in healthy beagle dogs.Methods: This was a cross-over study and all animals in the study were assigned to one of two treatment arms to receive either TJM-bimatoprost (n=6) or BKC-bimatoprost (n=6) ophthalmic solution. Dosing for period 1 was started on day 3 (8 am everyday) and it continued till day 12. Assessments were carried out every day at 8 am, 9 am, 2 pm and 8 pm throughout the study period till day 17.Results: For the pooled analysis (n=12 in each group) of period 1 and 2, there was a significant decrease (p<0.001) in mean intra-ocular (IOP) 1 hour post administration as compared to the baseline and this trend continued all throughout the study in both treatment arms. Twenty fours after last dose, on day 12, IOP measurements were 14.20±1.59 mmHg and 13.89±1.5 mmHg in the TJM-bimatoprost and the BKC-bimatoprost group respectively. The analysis of the primary end point revealed that 95% confidence interval for the between group differences in mean IOP values were well within the pre-defined equivalence margin of ±1.5 mmHg. In terms of safety, there was no difference in mean pupillary diameter in the TJM-bimatoprost and BKC-bimatoprost group.Conclusions: The results of this study enhance our understanding of the proprietary TJM technology by establishing efficacy and safety of TJM-bimatoprost in animal models.

Effects of Sedation by Intramuscular Administration of Medetomidine on Canine Abdominal Vascular System and Hepatic Parenchyma Imaging Using Enhancement Dynamic Computed Tomography

This prospective crossover study compared the effects of intramuscular administration of medetomidine for sedation on parameters of the abdominal vascular system, measured by enhancement computed tomography (CT), to those of propofol-induced sevoflurane maintenance anesthesia, as a control, in five clinically healthy adult male beagle dogs (11.4–12.8 kg). Each animal underwent both protocols at a 1-week interval. The enhancement (HU) and time to peak enhancement on CT were measured for the aorta (AO), caudal vena cava (CVC), portal vein (PV), and hepatic parenchyma (HP). The contrast effects in the AO, PV, and HP were significantly delayed under medetomidine sedation compared to the control anesthesia protocol. Particularly, the contrast effect in the PV and HP was significantly delayed under sedation, appearing approximately 1 min after contrast medium injection. This delay likely reflects the peripheral vasoconstrictive effect of medetomidine. We noted a generally early high contrast enhancement of the CVC under medetomidine sedation, likely contributed by the induced bradycardia. Therefore, findings obtained on contrast enhancement CT under medetomidine sedation may be different from those obtained under propofol-induced sevoflurane maintenance anesthesia. These differences are important to consider when using the findings to inform diagnosis.

Cisternal versus lumbar cerebrospinal fluid lactate concentration in healthy dogs

The analysis of cerebrospinal fluid biomarkers provides a wide range of information about the neurological health of a patient. Lactate is a metabolic precursor necessary for brain gluconeogenesis. When oxidative impairment or mitochondrial damage is present, lactate alteration occurs. The rostro-caudal dynamics of cerebrospinal biomarkers along the craniospinal axis in humans and horses was demonstrated in other studies. To the authors’ knowledge, no clinical study has, so far, investigated the cerebrospinal fluid lactate concentration in dogs in association with the puncture site. The purpose of this study was to compare the cerebellomedullary cistern and lumbar cistern cerebrospinal fluid lactate concentrations in healthy dogs. Cerebellomedullary and lumbar cerebrospinal fluids were collected for the cell count, total protein determination and lactate analysis from ten healthy Beagle dogs. The results revealed a significantly increased lumbar cerebrospinal fluid lactate concentration when compared with the cerebellomedullary cistern level. The results included: the total nucleated cell count < 5 cells/µl, the red blood cell count < 500 cell/µl, the total proteins < 0.3 g/l, as well as the cerebellomedullary lactate values (1.44 ± 0.06 mM/l) and the lumbar cistern lactate values (1.58 ± 0.1 mM/l). The results of this study highlight useful data that help to understand the physiological lactate variations depending on the cerebrospinal fluid puncture site.

Bone Regeneration Capability of 3D Printed Ceramic Scaffolds.

In this study, we evaluated the bone regenerative capability of a customizable hydroxyapatite (HA) and tricalcium phosphate (TCP) scaffold using a digital light processing (DLP)-type 3D printing system. Twelve healthy adult male beagle dogs were the study subjects. A total of 48 defects were created, with two defects on each side of the mandible in all the dogs. The defect sites in the negative control group (sixteen defects) were left untreated (the NS group), whereas those in the positive control group (sixteen defects) were filled with a particle-type substitute (the PS group). The defect sites in the experimental groups (sixteen defects) were filled with a 3D printed substitute (the 3DS group). Six dogs each were exterminated after healing periods of 4 and 8 weeks. Radiological and histomorphometrical evaluations were then performed. None of the groups showed any specific problems. In radiological evaluation, there was a significant difference in the amount of new bone formation after 4 weeks (p < 0.05) between the PS and 3DS groups. For both of the evaluations, the difference in the total amount of bone after 8 weeks was statistically significant (p < 0.05). There was no statistically significant difference in new bone between the PS and 3DS groups in both evaluations after 8 weeks (p > 0.05). The proposed HA/TCP scaffold without polymers, obtained using the DLP-type 3D printing system, can be applied for bone regeneration. The 3D printing of a HA/TCP scaffold without polymers can be used for fabricating customized bone grafting substitutes.

A moisturizer formulated with glycerol and propylene glycol accelerates the recovery of skin barrier function after experimental disruption in dogs.

BackgroundMoisturizers are foundational therapies for human atopic dermatitis. In veterinary medicine, the use of moisturizers has been recommended by an expert committee to alleviate skin dryness that would occur, for example, in canine atopic dermatitis (cAD). However, little is known regarding the effects of moisturizers on the skin barrier.Hypothesis/ObjectivesTo investigate the effects of a moisturizer on skin barrier recovery in a canine model of chronic mechanical barrier disruption.AnimalsSix healthy beagle dogs maintained in a laboratory setting.Methods and materialsA model of chronic skin barrier disruption was simulated by tape stripping on both sides of the thorax. The moisturizer then was applied twice daily for one week to one side of the thorax, while the other hemithorax was left untreated. The effects were evaluated by measurement of transepidermal water loss (TEWL) at various times during skin barrier recovery, and by histological assessment of the disrupted skin one week after moisturizer application.ResultsOverall, TEWL was reduced, epidermal thickness was lower, stratum corneum thickness was greater and the intensity of the dermal inflammatory infiltrate was reduced for treated sites.Conclusions and clinical importanceThese results suggest a potential benefit of the moisturizer for improving skin barrier function, which is frequently altered in chronic inflammatory dermatoses such as cAD.

Effects of Queso Blanco cheese containing Bifidobacterium longum KACC 91563 on fecal microbiota, metabolite and serum cytokine in healthy beagle dogs

The study describes the effects of administration of Queso Blanco cheese containing Bifidobacterium longum on the fecal microbiota, metabolite and serum cytokine in healthy beagle dogs. Twelve healthy beagle dogs were randomly divided in three groups of four dogs each:a control group, not fed with any cheese, and groups fed with Queso Blanco cheese with B. longum KACC 91563 (QCB) or without B. longum (QC) for 8 weeks. Fecal microbiota was analyzed using a culture-based method and 16s rRNA gene sequencing. Serum cytokine levels, activation of natural killer cells, and proliferation of peripheral blood mononuclear cells were determined. SPME-GC-MS method was used to determine the concentrations of short chain fatty acids and indole in dog feces. Administration of QCB for 4 weeks significantly increased the Bifidobacterium. QCB supplementation for 8 weeks reduceds Enterobacteriaceae and Clostridium perfringens (p < 0.05). The abundance of Fusobacterium, Blautia and Collinesella in QCB group were reduced as compared with the control group. Serum TNF-α and IL-6 levels at 8 weeks significantly increased in QCB group as compared with QC group. There was no change in the concentrations of total short chain fatty acids by B. longum at 0 and 4 weeks. At week 8, the acetic acid, propionic acid and butyric acid of the QCB and QC groups were significantly decreased compared to the control group. In conclusion, our results demonstrate that administration of QCB had positive effects on fecal microbiota and immune response in beagle dogs. We suggest that Queso Blanco cheese containing B. longum KACC 91563 could be used as a functional food for companion animals.

Effect of a lactate-guided conditioning program on heart rate variability obtained using 24-Holter electrocardiography in Beagle dogs.

The dogs’ responses to training exercise are seldom monitored using physiological variables, and cardiac autonomic regulation (CAR) is a relevant determinant of endurance-training adaptation. There are studies in the literature establishing that regular exercise could interfere with CAR in dogs, measured by heart rate and vagal-derived indexes of heart-rate-variability (HRV). However, few studies were found using a prescribed training program based on the lactate threshold (LT) to determine HRV by a 24-h Holter analysis. The purpose of this study was to test whether an endurance-training program (ETP) guided individually by LT raises time-domain measures of HRV in healthy Beagle dogs. Twenty dogs were assigned to two groups: control (C) and trained (T). The dogs from group T underwent an incremental exercise test (IET) to determine their LT. Both LT and velocity corresponding to the LT (VLT) was determined by visual inspection. T group performed an eight-week endurance-training program consisting of treadmill runs set to 70–80% of the VLT. Next, dogs from the group T have submitted to IET again. The maximal velocities (Vmax) at which achieved by the trained dogs in both IETs were determined. The group S did not undergo IETs or ETP. HRV was determined by the 24-hour-Holter at rest, before and on the 2°, 4°, 6° and 8° training weeks. To examine the HR impact on HRV, standard HRV variables were normalized to prevailing HR. VLT and Vmax rose in group T, indicating an improvement of dogs’ aerobic and anaerobic capacity. The normalized standard HRV indexes were relatively attenuated since these variables had a reduction in the degree of correlation concerning an average HR. The ETP resulted in decreased resting heart rate and increased time-domain indices, highlighting the log-transformed square root of the mean sum of the squared differences between R–R intervals (Ln rMSSD). The lactate-guided endurance-training program could lead to better parasympathetic cardiac modulation in Beagle dogs.

Novel contrast agent Visphere™ is feasible for contrast-enhanced ultrasonography in dogs.

Contrast-enhanced ultrasonography provides a more functional diagnostic image than conventional ultrasonography. This prospective exploratory study compared the novel contrast agent, Visphere™ , with commercial contrast agents in five healthy Beagle dogs. Visphere™ has the smallest diameter and highest concentration compared with Sonazoid® and SonoVue® . Each dog received an intravenous injection of Visphere™ , Sonazoid® , or SonoVue® . Images were recorded for 300, 600, and 60 s in the heart, liver, and left kidney, respectively. The mean pixel values of the regions of interest for each organ were expressed as time intensity curves (TIC). The agents all improved the visualization of left ventricular endocardial border delineation in the heart, and had similar TICs and clinical useful durations. In contrast, Visphere™ expressed the highest mean pixel value in the liver parenchyma at an early observation time and maintained the intensity until 600 s, like Sonazoid® . The renal evaluation results indicated there were no statistically significant differences in time-to-peak for the renal cortex or medulla among the agents. Compared with the other two agents, SonoVue® had the lowest peak enhancement for the renal cortex and medulla. No dogs had any adverse reactions during or after the study. All three agents provided adequate results for left ventricular endocardial border delineation, and Visphere™ may have the same potential as Sonazoid® to detect and characterize hepatic lesions. Visphere™ and Sonazoid® may offer better visualization quality to evaluate renal function. In conclusion, the novel contrast agent, Visphere™ , is comparable with commercial agents and could be applied in different major organs in dogs.

MRI perfusion analysis using freeware, standard imaging software

BackgroundPerfusion-weighted imaging is only scarcely used in veterinary medicine. The exact reasons are unclear. One reason might be the typically high costs of the software packages for image analysis. In addition, a great variability concerning available programs makes it hard to compare results between different studies. Moreover, these algorithms are tuned for their usage in human medicine and often difficult to adapt to veterinary studies.In order to address these issues, our aim is to deliver a free open source package for calculating quantitative perfusion parameters. We develop an “R package” calculating mean transit time, cerebral blood flow and cerebral blood volume from data obtained with freely imaging software (OsiriX Light®). We hope that the free availability, in combination with the fact that the underlying algorithm is open and adaptable, makes it easier for scientists in veterinary medicine to use, compare and adapt perfusion-weighted imaging analysis.In order to demonstrate the usage of our software package, we reviewed previously acquired perfusion-weighted images from a group of eight purpose-breed healthy beagle dogs and twelve client-owned dogs with idiopathic epilepsy. In order to obtain the data needed for our algorithm, the following steps were performed: First, regions of interest (ROI) were drawn around different, previously reported, brain regions and the middle cerebral artery. Second, a ROI enhancement curve was generated for each ROI using a freely available PlugIn. Third, the signal intensity curves were exported as a comma-separated-value file. These files constitute the input to our software package, which then calculates the PWI parameters.ResultsWe used our software package to re-assess perfusion weighted images from two previous studies. The clinical results were similar, showing a significant increase in the mean transit time and a significant decrease in cerebral blood flow for diseased dogs.ConclusionWe provide an “R package” for computing the main perfusion parameters from measurements taken with standard imaging software and describe in detail how to obtain these measurements. We hope that our contribution enables users in veterinary medicine to easily obtain perfusion parameters using standard Open Source software in a standard, adaptable and comparable way.

Evaluation of the Autonomic Nervous System in a Canine Model of Chronic Embolic Pulmonary Hypertension.

Sildenafil improves autonomic dysfunction caused by pulmonary hypertension (PH) in humans, but its effect is unknown in dogs with PH. This prospective study aimed to evaluate the autonomic nervous system function of a canine model of chronic embolic PH (CEPH) and the autonomic nervous system function of a canine model of CEPH in which sildenafil was administered. This study used five clinically healthy female beagle dogs. Evaluation parameters included hemodynamic parameters, heart rate (HR) and heart rate variability (HRV). Each evaluation parameter was compared before and after creating the CEPH model (before, BL; after, CEPHBL) and between the CEPHBL model and after the administration of sildenafil (1mg/kg, BID) in the CEPH model dogs (CEPHSil). In the CEPHBL model, the hemodynamic parameters indicated cardiac hypofunction, and HR was significantly increased and HRV was significantly decreased compared with BL. Further, in the CEPHSil model, the hemodynamic parameters suggested improvement in cardiac function, and HRV was significantly increased. From the results of the CEPH model dogs, autonomic dysfunction was shown to occur in PH dogs. In addition, the administration of 1mg/kg of sildenafil to CEPH model dogs may improve autonomic dysfunction.

Evaluation of Azygos Vein to Aorta Ratio using Multi-Detector Computed Tomography in Dogs

The purpose of this study is to evaluate the azygos vein to aorta diameter ratio (AV/AO ratio) in healthy dogs and dogs with diseases that may cause azygos vein dilation. The normal groups included eleven healthy beagle dogs and eleven small breed dogs. The abnormal group included 43 dogs that had diseases with high right atrial pressure (RA group), obstruction of cranial or caudal vena cava (CVC group) and porto-azygos shunt group (PSS group). The diameter of AV and AO were measured at three sites on thoracic CT images; the level of the cranial endplate of 12th thoracic vertebra (TV level), the tracheal bifurcation (TB level) and the insertion to the cranial vena cava (CrVC level). The AV/AO ratio at the CrVC level had significantly higher values than those at the TV and TB levels in the normal groups. The AV/AO ratios of TV and TB levels in the CVC group and the values at all measurement sites of the PSS group were significantly higher than the normal groups. AV/AO ratio will be a useful factor for the evaluation of various clinical conditions that change the AV diameter with respect independent to the body weight in dogs.

Resting state networks of the canine brain under sevoflurane anaesthesia.

Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs’ brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases.

Valores de referência de tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e fibrinogênio em cães hígidos da raça beagle

Background: Hemostasis is a process of blood coagulation with the function of preventing hemorrhagic processes in the organism. The Coagulation Time (CT), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen, Thrombin Time (TT), Increased Fibrin Degradation Products (IFDP) and D-Dimers are laboratory tests that can be used to evaluate the coagulation cascade. Objectives: The present study aimed to determine the reference values of PT, APTT and Fibrinogen by semi-automatic methodology with laboratorial kits. Methods: Blood samples were collected from 22 healthy beagle dogs and immediately centrifuged and citrated plasma stored at -20oC for posterior analysis. PT, APTT and fibrinogen were measured using commercial kits in a semi-automatic coagulometer by the viscosity detection system. Results: Mean values obtained were 6.0 ± 7.3 seconds for PT, 8.4 ± 16.9 seconds for APTT, and 10.2 ± 26.4 seconds for Fibrinogen. Conclusion: It is concluded that the values obtained in this work can be used as reference for healthy Beagles.

Biomechanical Effects of Tibial Plateau Levelling Osteotomy on Joint Instability in Normal Canine Stifles: An In Vitro Study.

The aim of the study was to determine the changes in biomechanical characteristics following tibial plateau levelling osteotomy (TPLO) using simulated manual tests. Twenty-one stifles from healthy Beagle dogs that had undergone TPLO or had not (control) were first tested in the intact form, and then the cranial cruciate ligament (CrCL) was transected in each to provide four test situations: control-intact, control-CrCL-transected, TPLO-intact and TPLO-CrCL-transected. The stifles were then analysed using a robotic joint biomechanical testing system. The craniocaudal drawer, axial rotation and proximal compression tests were applied. The craniocaudal displacement during the drawer test was not significantly different between the control-intact and TPLO-intact. However, the displacement was significantly greater in the TPLO-CrCL-transected than in the control-intact. In the axial rotation test, the internal-external (IE) rotation was significantly greater in the TPLO-intact than in the control-intact. Similarly, the IE rotation was significantly greater in the TPLO-CrCL-transected than in the control-CrCL-transected. In the proximal compression test, craniocaudal displacement was not significantly different among the control-intact, TPLO-intact and TPLO-CrCL-transected. These findings suggest that TPLO influences the tension of the collateral ligaments and might generate laxity of the tibiofemoral joint. Instability after the osteotomy might be associated with the progression of osteoarthritis.

Tragus Nerve Stimulation Suppresses Post-Infarction Ventricular Arrhythmia by Modulating Autonomic Activity and Heterogeneities of Cardiac Receptor Distribution.

BackgroundImbalanced cardiac autonomic control and cardiac receptors redistribution contribute to the arrhythmogenic substrate under the myocardial infarction (MI) condition. Stimulating the auricular branch of vagus nerve (AB-VNS) has been proven to reduce post-infarction ventricular arrhythmia (VAs), but its potential mechanisms were largely unknown.This study aimed to investigate whether long-term intermittent low-intensity AB-VNS could produce a protective effect on modulating autonomic activities and abnormal redistribution of autonomic nerve efferent receptors in a MI canine model.Material/MethodsTwelve healthy beagle dogs underwent ligation of the left anterior descending coronary artery to establish a MI model and were randomized into 2 groups: an AB-VNS group, (AB-VNS for 4 weeks) and a control group (sham stimulation for 4 weeks). Dynamic electrocardiogram recording, neural recording, catecholamine concentration, and histological studies were conducted subsequently.ResultsCompared to the control group, the AB-VNS group had significantly suppressed post-infarction VAs, reduced low frequency (LF) power and increased high frequency (HF) power. In the AB-VNS group, with the progression of reduced cardiac sympathetic activities and augmented cardiac parasympathetic activities, the catecholamine concentration in heart tissue declined in the peripheral infarction area and right ventricle (RV); tyrosine hydroxylase (TH)-positive neurons decreased in the inferior cardiac sympathetic nerve, and choline acetyltransferase (ChAT)-positive neurons increased in the cervical vagus nerve. Expression of TrkA and P75NGFR were reduced in the peripheral MI (peri-MI) and non-MI area with AB-VNS. The mRNA expression of adrenergic and nicotinic receptors (β1-AR, β3-AR, and CHRNA7) significantly declined in the peri-MI and non-MI area of the AB-VNS group.ConclusionsChronic intermittent low-intensity AB-VNS effectively suppressed post-infarction VAs by potentially rebalancing extracardiac intrathoracic autonomic activities, reducing excessive cardiac sympathetic denervation, and attenuating the heterogeneities of cardiac efferent nerve receptors distribution.