Echocardiographic assessments of longitudinal left ventricular function in healthy English springer spaniels

OBJECTIVES: To establish reference intervals for echocardiographic measures of longitudinal left ventricular function in adult English springer spaniel dogs. ANIMALS: Forty-two healthy adult English springer spaniels. METHODS: Animals were prospectively recruited from a general practice population in the United Kingdom. Dogs were examined twice, at least 12 months apart, to exclude dogs with progressive cardiac disease. Mitral annular plane systolic excursion, tissue Doppler imaging (TDI) mitral annular velocities and two-dimensional speckle-tracking echocardiographic (2DSTE) left ventricular longitudinal strain and strain rate were measured. Intraoperator and intraobserver variability were examined and reference intervals were calculated. The potential effects of body weight, age and heart rate on these variables were examined. RESULTS: Intraoperator and intraobserver variability was <10% for all parameters except TDI E’ and 2DSTE variables, which were all <20%. Thirty-nine dogs were used to create reference intervals. Significant (but mostly weak) effects of age, heart rate and body weight on were detected. Reference intervals were similar to previously published values In different breeds. CLINICAL SIGNIFICANCE: Breed specific reference intervals for measures of longitudinal left ventricular function in the English springer spaniel are presented

Investigation Of Murine Esophageal Myogenesis

This work focuses on the development of the muscular layers of the murine esophagus. Considerable controversy surrounds the manner in which the muscularis externa of the esophagus develops, ever since investigators proposed the rare phenomenon of transdifferentiation as a mechanism for virtually complete replacement of smooth muscle by striated muscle that is observed in the murine esophagus. I found, using several independent levels of evidence, that transdifferentiation is an unlikely explanation for esophageal myogenesis. First, by fate-mapping smooth muscle cells, I failed to observe expression of the fate-mapping marker in any esophageal striated muscle. Second, I failed to co-localize expression of smooth-muscle-specific and striated-muscle-specific proteins in any cell undergoing differentiation into a striated muscle lineage. Finally, selective deletion of a critical striated muscle transcription factor (myogenin) in esophageal smooth muscle cells prior to the appearance of any striated muscle failed to arrest subsequent esophageal striated myogenesis. To address prior concerns of the fate of esophageal smooth muscle, I examined smooth muscle morphology in transgenic mice expressing smoothmuscle-specific eGFP, and identified 3 possible fates: (A) the incorporation of smooth muscle cells into the striated muscle stroma as ?remnant? smooth muscles; (B) compaction and persistence of smooth muscle cells in the pre- gastric region; and (C) occasional apoptosis of smooth muscle cells. Using exhaustive co-immunolabeling methods, I demonstrated that remnant smooth muscle cells are indeed a previously unidentified cell population resident within the striated esophageal musculature. Finally, I examined the origin of striated muscle precursors in a series of ex vivo experiments. I was able to maintain a functional esophageal phenotype in culture for up to 7 days, and determined that striated muscle precursors most likely populate the esophageal muscularis externa early in development, and are subsequently induced to express a myogenic program in a craniocaudal direction. Together, these findings extend the understanding of esophageal myogenesis and redress fundamental concepts of myogenesis, namely, transdifferentiation, by providing evidence of a more simple, classical myogenic program in this unique muscular organ

Felbamate as an oral add-on therapy in six dogs with presumptive idiopathic epilepsy and generalized seizures resistant to drug therapy

Background: Idiopathic or genetic epilepsy commonly affects dogs; affected dogs are often refractory to anti-seizure drug therapy. Felbamate is an anti-seizure drug with established pharmacokinetic and safety data for dogs, but little published evidence of efficacy for managing generalized seizures in this species.Aim: The purpose of this retrospective case series was to evaluate the clinical efficacy and tolerability of oral felbamate in six presumptive epileptic dogs experiencing generalized seizures.Methods: Medical records from six dogs with presumptive idiopathic/genetic epilepsy manifesting as generalized seizure activity, for which oral felbamate was used as an add-on treatment, were reviewed. The number of seizures recorded for the 3-month period immediately before instituting felbamate was recorded for each dog. Short-term (3 months) and long-term (6 months or greater) seizure frequency post-felbamate therapy was recorded for each dog and compared with baseline.Results: Overall, dogs experienced a reduction (82%) in seizures after adding felbamate in the short term, with 5/6 dogs (83%) classified as responders (50% or greater reduction in seizures) and 3/6 dogs (50%) attaining seizure-free status. Mean and median long-term follow-up times were 13 and 11 months, respectively (range: 6 to 23 months). Four of the 6 dogs (67%) remained drug responders at final follow-up, with an average seizure reduction of 98%, 2 of which remained seizure-free at 8 and 21 months. Two dogs (33%) experienced increased seizure activity during long-term follow-up (12 and 23 months) and were considered non-responders. The non-responder dogs had an average long-term seizure reduction of 33%. No dog experienced any obvious adverse effects associated with felbamate administration. However, one dog not included in the analysis because of insufficient (&lt;3 month) post-felbamate follow-up, was weaned off felbamate because of suspected hepatotoxicity.Conclusion: Our small case series suggests that oral felbamate might show promise as an add-on drug for epileptic dogs experiencing generalized seizures resistant to drug therapy. These results warrant a more controlled, prospective investigation into felbamate as a therapeutic agent for canine epilepsy

Effect of Body Position on the 6-Lead ECG of Dogs

ECGs recorded from dogs show characteristic morphology and changes in morphology with various disease states. These changes are determined by comparing individual recordings to reference ranges established from recordings obtained from normal dogs in right lateral (RL) recumbency. Using these reference ranges for ECGs recorded from dogs in other positions may not be valid. We compared ECG complexes from 39 normal dogs obtained in RL, left lateral (LL), and standing (ST) body positions. ECGs from dogs in ST position showed increased Q-wave and R-wave amplitudes in leads I and II, increased R-wave and S-wave amplitudes in leads aVR and aVL, and decreased R-wave and S-wave amplitudes in lead III when compared with recordings obtained in RL position. ECGs from dogs in LL position showed increased R-wave amplitude in leads II, III, and aVF and S-wave amplitude in lead aVL but decreased R-wave amplitude in lead aVR when compared with recordings obtained in RL position. The mean electrical axis (MEA) shifted to the left in ST position but remained within the normal range in LL position. We determined that both a change in the relative position of the recording electrodes with respect to the heart as well as a change in intrathoracic cardiac position contributed to these changes. P-wave amplitude, P-R and S-T intervals, and QRS complex durations remained unaltered by changes in body position. Our findings indicate that ECGs of dogs recorded in RL, LL, and ST positions yield dramatically different results, and investigators should use position-specific reference ranges to minimize potential misinterpretation of ECG results

Attitudes of small animal practitioners toward participation in veterinary clinical trials

To determine attitudes of small animal practitioners toward veterinary clinical trials and variables influencing their likelihood of participating in such trials

US Veterinarians' Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions

Due to the myriad of laws concerning cannabis, there is little empirical research regarding the veterinary use of cannabidiol (CBD). This study used the Veterinary Information Network (VIN) to gauge US veterinarians' knowledge level, views and experiences related to the use of cannabinoids in the medical treatment of dogs. Participants (n = 2130) completed an anonymous, online survey. Results were analyzed based on legal status of recreational marijuana in the participants' state of practice, and year of graduation from veterinary school. Participants felt comfortable in their knowledge of the differences between Δ9-tetrahydrocannabinol (THC) and marijuana, as well as the toxic effects of marijuana in dogs. Most veterinarians (61.5%) felt comfortable discussing the use of CBD with their colleagues, but only 45.5% felt comfortable discussing this topic with clients. No differences were found based on state of practice, but recent graduates were less comfortable discussing the topic. Veterinarians and clients in states with legalized recreational marijuana were more likely to talk about the use of CBD products to treat canine ailments than those in other states. Overall, CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures. Veterinarians practicing in states with legalized recreational marijuana were more likely to advise their clients and recommend the use of CBD, while there was no difference in the likelihood of prescribing CBD products. Recent veterinary graduates were less likely to recommend or prescribe CBD. The most commonly used CBD formulations were oil/extract and edibles. These were most helpful in providing analgesia for chronic and acute pain, relieving anxiety and decreasing seizure frequency/severity. The most commonly reported side-effect was sedation. Participants felt their state veterinary associations and veterinary boards did not provide sufficient guidance for them to practice within applicable laws. Recent graduates and those practicing in states with legalized recreational marijuana were more likely to agree that research regarding the use of CBD in dogs is needed. These same groups also felt that marijuana and CBD should not remain classified as Schedule I drugs. Most participants agreed that both marijuana and CBD products offer benefits for humans and expressed support for use of CBD products for animals

Pharmacokinetics of Single-Dose Oral Pregabalin Administration in Normal Cats

Objective: To describe the pharmacokinetic parameters of oral pregabalin in normal cats after single oral dosing.Animals: Six healthy adult research cats.Procedures: Following sedation and indwelling catheter placement, one oral (4 mg/kg) dose of pregabalin was administered. Blood samples were collected at 0, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 h after administration. Plasma pregabalin concentrations were measured by high-performance liquid chromatography and subjected to pharmacokinetic analysis using commercial software.Results: Four of six cats developed moderate sedation after pregabalin administration. The peak pregabalin concentration was 8.3 ± 1.6 μg/ml which occurred at 2.9 ± 1.2 h. Elimination half-life was 10.4 ± 2.6 h and area under the curve was 133.9 ± 71.5 μg-h/ml. Time above the minimum therapeutic concentration for seizure control in dogs and people (2.8 μg/ml) was 17.6 ± 6.2 h. Using these data, predicted minimum, maximum and average steady state concentrations were calculated for 12 and 24 h dosing intervals.Conclusions and Clinical Relevance: Pregabalin (4 mg/kg) administered orally to cats results in plasma concentrations within the range considered to be efficacious for seizure control in dogs and humans between 1.5 and at least 12 h. Because of moderate sedative side effects in the majority of cats at this dose and high calculated maximum steady state concentrations, a lower dose, given more frequently (1–2 mg/kg q 12 h), should be evaluated in prospective clinical studies

The genetic basis of hypertrophic cardiomyopathy in cats and humans

Mutations in genes that encode for muscle sarcomeric proteins have been identified in humans and two breeds of domestic cats with hypertrophic cardiomyopathy (HCM). This article reviews the history, genetics, and pathogenesis of HCM in the two species in order to give veterinarians a perspective on the genetics of HCM. Hypertrophic cardiomyopathy in people is a genetic disease that has been called a disease of the sarcomere because the preponderance of mutations identified that cause HCM are in genes that encode for sarcomeric proteins (Maron and Maron, 2013). Sarcomeres are the basic contractile units of muscle and thus sarcomeric proteins are responsible for the strength, speed, and extent of muscle contraction. In people with HCM, the two most common genes affected by HCM mutations are the myosin heavy chain gene (MYH7), the gene that encodes for the motor protein β-myosin heavy chain (the sarcomeric protein that splits ATP to generate force), and the cardiac myosin binding protein-C gene (MYBPC3), a gene that encodes for the closely related structural and regulatory protein, cardiac myosin binding protein-C (cMyBP-C). To date, the two mutations linked to HCM in domestic cats (one each in Maine Coon and Ragdoll breeds) also occur in MYBPC3 (Meurs et al., 2005, 2007). This is a review of the genetics of HCM in both humans and domestic cats that focuses on the aspects of human genetics that are germane to veterinarians and on all aspects of feline HCM genetics

The term "Pilot Study" is misused in veterinary medicine: a critical assessment

Authors commonly use the term ‘Pilot Study’ in the veterinary literature. The term has a specific definition in medical literature, but is not defined in veterinary literature. Therefore, we sought to examine the frequency of the use of the term and the characteristics of studies using the term in the article title, and derive the intended meaning of the term. We identified all articles in veterinary literature using the term in the article title between 2008 and 2017. We then examined specific characteristics of articles published between 2008 and 2012. We found use of the term is increasing (P<0.0001). Of articles using the term between 2008 and 2012, only 20 per cent led to a larger, more comprehensive verifying study. Most garnered few citations, but 75 per cent were cited in review articles. Pilot studies had a median sample size of 10 subjects. We found comparable studies for each pilot study that did not incorporate the term into their titles. None of the authors of any of the pilot studies defined the term or explained why their study was termed a ‘pilot study’. Journals and authors used the term haphazardly. Our findings indicate that the term ‘Pilot Study’ is meaningless because it meets no specific, consistently adhered-to criteria. We believe that authors use the term as a means of ‘Deficiency signaling’ to editors, reviewers and readers. We recommend that authors and journals abandon the term in veterinary literature because it serves no purpose, is not used consistently and might harm veterinary medicine.Non

Left ventricular volume estimates by two-dimensional echocardiography

Data are presented in XL. All initial measurements are in mm unless otherwise specified.This dataset comprises 224 dogs, imaged for a study to be published.Non