Complex Feline Disease Mapping Using a Dense Genotyping Array.

The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals.

Insights into sinus arrhythmia of the dog: Acetylcholine perfusion of canine right atrium results in beat-to-beat patterns that mimic sinus arrhythmia supporting exit block in the sinoatrial conduction pathways.

Sinus arrhythmia of the dog is unique because of the pronounced alternating beat-to-beat intervals. The clustering of these short (faster rates) and long (slower rates) intervals is not just influenced by autonomic input from breathing; sinus arrhythmia can persist in the panting or apneic dog. The multiplicity of central and peripheral influences on the sinus node complicates the unraveling of the mechanisms of sinus arrhythmia.

Comparison of the prevalence of Toxocara egg shedding by pet cats and dogs in the U.S.A., 2011-2014.

County based prevalence maps were produced using the annual data from the years 2011 through 2014 of the prevalence of Toxocara egg shedding in more than 500,000 pet cat and 2.5 million pet dog fecal samples submitted to centralized testing laboratories. Fecal examination results were obtained at these centers through examination of the samples by centrifugal floatation and microscopy, and were previously reported as annual data on the Companion Animal Parasite Council (CAPC) website.

Ranolazine effectively suppresses atrial fibrillation in the setting of heart failure.

Background: There is a critical need for safer and more effective pharmacological management of atrial fibrillation (AF) in the setting of heart failure (HF).

Methods And Results: This study investigates the electrophysiological, antiarrhythmic, and proarrhythmic effects of a clinically relevant concentration of ranolazine (5 μmol/L) in coronary-perfused right atrial and left ventricular preparations isolated from the hearts of HF dogs. HF was induced by ventricular tachypacing (2-6 weeks at 200-240 beats per minute; n=17).

A temporal window of vulnerability for development of atrial fibrillation with advancing heart failure.

Aims: Heart failure (HF) is associated with development of AF and life-threatening ventricular tachycardia and fibrillation (VT/VF). Vulnerability to development of AF and VT/VF at different stages of HF and the underlying pathophysiological mechanisms are poorly defined. The present study was designed to determine the time-course of development of electrical and structural remodelling of the atria and ventricles, and their contribution to induction of AF and VT/VF in a canine model of HF.

Change in β-catenin localization suggests involvement of the canonical Wnt pathway in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease with high prevalence in the Boxer dog population. It is characterized by replacement of the myocardium with fatty or fibro-fatty tissue. Several mechanisms for the development of ARVC have been suggested, including dysfunction of the canonical Wnt pathway, which is linked to many cellular functions, including growth and differentiation of adipocytes.

Cardiomyocyte calcium cycling in a naturally occurring German shepherd dog model of inherited ventricular arrhythmia and sudden cardiac death.

Objective: To further characterize arrhythmic mechanisms in German shepherd dogs (GSDs) affected with inherited ventricular arrhythmias by evaluating intracellular calcium cycling and expression of calcium handling genes.

Animals: Twenty five GSDs, 9 backcross dogs, and 6 normal mongrel dogs (controls) were studied. The GSDs and backcross dogs were from a research colony of inherited ventricular arrhythmias.

Physiological consequences of transient outward K+ current activation during heart failure in the canine left ventricle.

Background: Remodeling of ion channel expression is well established in heart failure (HF). We determined the extent to which I(to) is reduced in tachypacing-induced HF and assessed the ability of an I(to) activator (NS5806) to recover this current.

Method And Results: Whole-cell patch clamp was used to record I(to) in epicardial (Epi) ventricular myocytes.

Use of computed tomography and silicon endocasts to identify pulmonary veins with echocardiography.

The pulmonary veins were identified from the silicone endocast heart models of 19 dogs. Although variation in the number of the more peripheral veins on each specimen existed, all of the casts had a consistency with regards to the most proximal coalescence of the pulmonary veins as they entered the body of the left atrium. That is, the confluence of the veins formed three ostia at the atrial entry point that consisted of 1) right cranial and right middle pulmonary lobe veins; 2) right caudal, accessory, and left caudal pulmonary lobe veins; and 3) both the left cranial and left caudal pulmonary lobe veins of the left cranial lung lobe.

Interactions between TGFβ1 and cyclic strain in modulation of myofibroblastic differentiation of canine mitral valve interstitial cells in 3D culture.

Objectives: The mechanisms of myxomatous valve degeneration (MVD) are poorly understood. Transforming growth factor-beta1 (TGFβ1) induces myofibroblastic activation in mitral valve interstitial cells (MVIC) in static 2D culture, but the roles of more physiological 3D matrix and cyclic mechanical strain are unclear. In this paper, we test the hypothesis that cyclic strain and TGFβ1 interact to modify MVIC phenotype in 3D culture.

The mechanobiology of mitral valve function, degeneration, and repair.

In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation.

Fluorescence in-situ hybridization for the identification of bacterial species in archival heart valve sections of canine bacterial endocarditis.

Bacterial endocarditis (BE) is defined as inflammation of cardiac valve structures and/or the endocardium secondary to bacterial infection. Canine valvular BE is associated with significant morbidity and mortality and ante-mortem diagnosis and post-mortem identification of causative organisms is problematic. Identification of bacteria in canine BE has traditionally relied on visualization of organisms on histological sections stained with haematoxylin and eosin (HE), Gram and modified Steiner's stains.

Low-energy control of electrical turbulence in the heart.

Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure.

Ultrastructural changes in cardiac myocytes from Boxer dogs with arrhythmogenic right ventricular cardiomyopathy.

Objectives: We sought to quantify the number and length of desmosomes, gap junctions, and adherens junctions in arrhythmogenic right ventricular cardiomyopathy (ARVC) and non-ARVC dogs, and to determine if ultrastructural changes existed.

Animals: Hearts from 8 Boxer dogs afflicted with histopathologically confirmed ARVC and 6 dogs without ARVC were studied.

Methods: Quantitative transmission electron microscopy (TEM) and Western blot semi-quantification of α-actinin were used to study the intercalated disc and sarcomere of the right and left ventricles.

The effects of pentoxifylline on equine platelet aggregation.

Background: Pentoxifylline (PTX) possesses a number of vasomotor, immunomodulatory, and hemorheologic properties. Based upon the hypothesis that equine laminitis and navicular disease result from microthrombosis, the inhibitory effects of PTX on inflammatory cytokines, and its inhibitory effects on human platelet aggregation, PTX has been widely used to treat equine endotoxemia, navicular disease, and laminitis. Despite this, the effects of PTX on equine platelet aggregation have not been investigated previously.

Termination of equine atrial fibrillation by quinidine: an optical mapping study.

Objective: To perform the first optical mapping studies of equine atrium to assess the spatiotemporal dynamics of atrial fibrillation (AF) and of its termination by quinidine.

Animals: Intact, perfused atrial preparations obtained from four horses with normal cardiovascular examinations.

Materials And Methods: AF was induced by a rapid pacing protocol with or without acetylcholine perfusion, and optical mapping was used to determine spatial dominant frequency distributions, electrical activity maps, and single-pixel optical signals.

The patch clamp technique: principles and technical considerations.

The development of techniques that allow the high fidelity measurement of small scale ionic currents ushered in a new era of investigation into the role of ion channels in the physiologic and pathophysiologic function of excitable tissue. Based upon the formation of a high resistance (gigaohm) seal with the membrane of the cell being studied, these "patch clamp" techniques have improved our understanding of a wide variety of cardiac disease states with respect to diagnosis, treatment and prognosis. This review outlines the basic principles underlying the patch clamp technique, including the properties of biological membranes and ion channels, and provides an elementary summary of its application to the recording of cardiac ionic currents, with a particular focus on issues related to myocyte isolation, electrode manufacturing and the voltage clamp configuration.

Identification of C-terminal domain residues involved in protein kinase A-mediated potentiation of kainate receptor subtype 6.

Glutamate receptors are the major excitatory receptors in the vertebrate CNS and have been implicated in a number of physiological and pathological processes. Previous work has shown that glutamate receptor function may be modulated by protein kinase A (PKA)-mediated phosphorylation, although the molecular mechanism of this potentiation has remained unclear. We have investigated the phosphorylation of specific amino acid residues in the C-terminal cytoplasmic domain of the rat kainate receptor subtype 6 (GluR6) as a possible mechanism for regulation of receptor function.

Pulmonary thromboembolism in cats.

Pulmonary thromboembolism (PTE) is rarely diagnosed in cats, and the clinical features of the disease are not well known. PTE was diagnosed at postmortem examination in 17 cats, a prevalence of 0.06% over a 24-year period.

The calcimimetic R-467 potentiates insulin secretion in pancreatic beta cells by activation of a nonspecific cation channel.

The extracellular, G protein-linked Ca(2+)-sensing receptor (CaSR), first identified in the parathyroid gland, is expressed in several tissues and cells and can be activated by Ca(2+) and some other inorganic cations and organic polycations. Calcimimetics such as NPS (R)-N-(3-phenylpropyl)-alpha-methyl-3-methoxybenzylamine hydrochloride (R-467), a phenylalkylamine, are thought to activate CaSR by allosterically increasing the affinity of the receptor for Ca(2+). When tested for its effect on insulin release in C57BL/6 mice, R-467 had no effect under basal conditions but enhanced both phases of glucose-stimulated release.

A syndrome resembling idiopathic noncirrhotic portal hypertension in 4 young Doberman pinschers.

We describe 4 young male Doberman Pinschers (3 littermates and 1 unrelated dog) with a syndrome resembling idiopathic or noncirrhotic portal hypertension of humans. Each dog was evaluated for a hepatopathy resulting in portal hypertension, development of portosystemic collateral vessels, and hepatic encephalopathy. These dogs differ from previous reports of young dogs with hepatic insufficiency associated with portal hypertension and acquired portal systemic shunting by their lack of intrahepatic arteriovenous fistulae, portal vein atresia, or intrahepatic fibrosis.

Right atrioventricular valve malformation in dogs and cats: an electrocardiographic survey with emphasis on splintered QRS complexes.

The purposes of this study were 2-fold: (1) to determine the prevalence of splintered QRS complexes (Rr', RR', rR', rr') and other electrocardiographic abnormalities in dogs and cats with congenital right atrioventricular valve malformation (RAVM) and (2) to determine if the Labrador Retriever was at greater risk for RAVM and splintered QRS complexes. EKGs from 39 dogs and 6 cats with echocardiographically diagnosed RAVM were studied retrospectively. Splintered QRS complexes were commonly found in affected Labrador Retrievers (9 of 19, 47%), non-Labrador Retrievers (12 of 20, 60%), and cats (4 of 6, 67%).

Age dependence of the development of ventricular arrhythmias in a canine model of sudden cardiac death.

Objectives: The age-dependence of the development of ventricular arrhythmias was studied in German shepherd dogs with inherited ventricular arrhythmias and sudden death.

Background: A colony of German shepherd dogs has been established that exhibit inherited ventricular arrhythmias and sudden death. The incidence of arrhythmias increases with age.

Inherited ventricular arrhythmias and sudden death in German shepherd dogs.

Objectives: This report describes a unique group of German shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure.

Background: There are few spontaneous animal models of sudden death that permit intensive investigation.