Publications by authors named "Meg Sleeper"

Sudden cardiac death in the young (SCDY) is a devastating event that often has an underlying genetic basis. Manchester Terrier dogs offer a naturally occurring model of SCDY, with sudden death of puppies as the manifestation of an inherited dilated cardiomyopathy (DCM). We performed a genome-wide association study for SCDY/DCM in Manchester Terrier dogs and identified a susceptibility locus harboring the cardiac ATP-sensitive potassium channel gene .

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Humans have a larger energy budget than great apes, allowing the combination of the metabolically expensive traits that define our life history. This budget is ultimately related to the cardiac output, the product of the blood pumped from the ventricle and the number of heart beats per minute, a measure of the blood available for the whole organism physiological activity. To show the relationship between cardiac output and energy expenditure in hominid evolution, we study a surrogate measure of cardiac output, the aortic root diameter, in humans and great apes.

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Captive chimpanzees (Pan troglodytes) mature earlier in body mass and have a greater growth rate compared to wild individuals. However, relatively little is known about how growth parameters compare between chimpanzees living in different captive environments. To investigate, body mass was measured in 298 African sanctuary chimpanzees and was acquired from 1030 zoological and 442 research chimpanzees, using data repositories.

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Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part of a proactive monitoring plan, zoological managers and veterinarians often elect to perform electrocardiograms (ECGs) on their great ape populations. ECGs noninvasively evaluate cardiac electrical activity, and are thereby capable of providing information regarding heart function.

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Cardiovascular disease (CVD) has been identified as a major cause of mortality in all four great ape taxa in zoologic institutions. In an effort to better understand and treat CVD in captive great apes, a program called the Great Ape Heart Project (GAHP), based at Zoo Atlanta, collects and maintains a database of echocardiograms and other relevant medical information relating to the cardiac health status of great apes. Cardiac health assessments have become standard practice among North American zoos that house great apes and are recommended by all four great ape Species Survival Plans (SSP) for the assessment of CVD in captive great apes.

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Objectives: The aim of this study was to determine the pharmacokinetics of furosemide in cats following intravenous (IV), oral and transdermal administration.

Methods: This study used six healthy adult cats in a three-phase design to compare plasma furosemide concentrations in cats that received one IV 2 mg/kg dose of furosemide, one oral 2 mg/kg dose of furosemide and 3 days of q12h dosing with 2 mg/kg furosemide transdermally applied to the ear pinna.

Results: After IV administration the elimination half-life was (mean and coefficient of variation) 2.

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A 2-year-old male intact Belgian Malinois was presented for exercise intolerance. A grade III/VI left basilar systolic murmur was detected. Echocardiography revealed moderate right atrial and ventricular dilation and increased pulmonic outflow velocity.

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Gene therapy is a procedure resulting in the transfer of a gene into an individual's cells to treat a disease. One goal of gene transfer is to express a functional gene when the endogenous gene is inactive. However, because heart failure is a complex disease characterized by multiple abnormalities at the cellular level, an alternate gene delivery approach is to alter myocardial protein levels to improve function.

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Equine Cardiovascular Therapeutics.

Vet Clin North Am Equine Pract

April 2017

Heart disease can be defined as any abnormality of the heart whether it is a cardiac dysrhythmia or structural heart disease, either congenital or acquired. Heart failure occurs when a cardiac abnormality results in the inability of the heart to pump enough blood to meet the body's needs. Heart disease can be present without leading to heart failure.

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Cardiovascular disease is a leading cause of death in captive chimpanzees and is often associated with myocardial fibrosis, which increases the risk of cardiac arrhythmias. In this case report, we present a 36-y-old male chimpanzee (Pan troglodytes) diagnosed with frequent ventricular premature complexes (VPC). We placed a subcutaneous implantable loop recorder for continual ECG monitoring to assess his arrhythmias without the confounding effects of anesthetics.

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Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes.

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A 10-year-old male neutered cavalier King Charles Spaniel with a 1-year history of degenerative mitral valve disease presented for dyspnea and severe weakness. He was diagnosed with congestive heart failure, systolic dysfunction, presumptive myocardial infarction and a left atrial thrombus based on thoracic radiographs, electrocardiogram and echocardiographic findings. Clinical signs also suggested right foreleg embolism.

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Objective: To determine whether echocardiographic variables differed between successful (elite) and less successful (nonelite) Arabian endurance horses.

Animals: 34 Arabian horses that competed in endurance racing.

Procedures: Horses were assigned to either an elite or nonelite group on the basis of results of a previous competition, and a standardized echocardiographic examination was performed on each horse within 1 to 4 weeks after that competition.

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This study evaluated whether acepromazine or methadone reduced behavioral parameters, overall excitement, and activity associated with midazolam administration to healthy dogs. Dogs received midazolam (M) alone [M: 0.25 mg/kg body weight (BW)] or with methadone (MM) (MM: 0.

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Objective: To generate reference ranges for echocardiographic variables in clinically normal adult chimpanzees (Pan troglodytes).

Design: Retrospective cohort study.

Animals: 88 clinically normal adult chimpanzees.

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Objective: To determine whether measurement of blood cardiac troponin I (cTnI) concentrations with a cage-side analyzer could be used to differentiate cardiac from noncardiac causes of dyspnea in cats.

Design: Prospective, multicenter study.

Animals: 44 client-owned cats with dyspnea and 37 healthy staff-owned cats.

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Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into the blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT).

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Mucopolysaccharidosis VII (MPS VII) is due to the deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiovascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed.

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Dystrophin-deficient muscles suffer from free radical injury, mitochondrial dysfunction, apoptosis, and inflammation, among other pathologies that contribute to muscle fiber injury and loss, leading to wheelchair confinement and death in the patient. For some time, it has been appreciated that endurance training has the potential to counter many of these contributing factors. Correspondingly, numerous investigations have shown improvements in limb muscle function following endurance training in mdx mice.

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Objective: To assess the effectiveness of the vertebral heart scale (VHS) system to differentiate congestive heart failure from other causes of dyspnea in cats.

Design: Retrospective case series.

Animals: 67 cats with acute respiratory distress.

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Objective: To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy.

Sample: Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy).

Procedures: Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs.

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Mucopolysaccharidosis (MPS) VI is due to a deficiency in the activity of N-acetylgalactosamine 4-sulfatase (4S), also known as arylsulfatase B. Previously, retroviral vector (RV)-mediated neonatal gene therapy reduced the clinical manifestations of MPS I and MPS VII in mice and dogs. However, sulfatases require post-translational modification by sulfatase-modifying factors.

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Three eight-week-old Golden Retriever puppy littermates were evaluated because of left basilar systolic murmurs and were diagnosed with primary infundibular stenosis. Pedigree analysis in this line was also performed to identify a mode of inheritance. All dogs were asymptomatic at the time of diagnosis; two of the three had congenital lesions in addition to primary infundibular stenosis.

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Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated in the mdx mouse, restoration of cardiac dystrophin expression in large animal models of Duchenne muscular dystrophy (DMD) has proven to be a challenge. In large animals, investigators have focused on using intravenous injection of antisense oligonucleotides (AO) to mediate exon skipping. In this study, we sought to optimize restoration of cardiac dystrophin expression in the golden retriever muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA) carrying antisense sequence to target the exon splicing enhancers of exons 6 and 8 and correct the disrupted reading frame.

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Cardiovascular disease in general, and cardiac arrhythmias specifically, is common in great apes. However, the clinical significance of arrhythmias detected on short-duration electrocardiograms is often unclear. Here we describe the use of an implantable loop recorder to evaluate cardiac rhythms in 4 unanesthetized adult chimpanzees (Pan troglodytes), 1 with a history of possible syncope and 3 with the diagnosis of multiform ventricular ectopy (ventricular premature complexes) and cardiomyopathy.

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