First reported case of a histiocytic sarcoma in an Armenian hamster (Cricetulus migratorius).

A 14-month-old male Armenian hamster (Cricetulus migratorius) presented with a spontaneous, subcutaneous, firm mass (4.0 × 2.0 × 1.5 cm) on the ventral neck extending towards the cheek pouch causing multifocal small oral ulcerations. This animal was immunized subcutaneously on the dorsal neck for the development of monoclonal antibodies seven months before presentation. The animal was euthanized and necropsy was performed. Histopathology of the mass showed a well demarcated, multilobulated, unencapsulated, highly cellular, neoplastic mass composed of spindle cells arranged in interlacing streams and bundles, with a moderate amount of fibrovascular stroma. The neoplastic cells exhibited indistinct cell borders and a moderate to large amount of eosinophilic, fibrillar cytoplasm, marked anisocytosis and anisokaryosis, binucleated and multinucleated cells, and high mitotic rate. Based on the histomorphologic features of the mass, and the presence of renal tubular hyaline globules and myeloid hyperplasia in the bone marrow, a diagnosis of histiocytic sarcoma was made. The presumptive diagnosis was confirmed by immunohistochemistry, upon which the neoplastic cells showed strong immunoreactivity for the histiocytic cell markers Iba1 and CD11b. Histiocytic sarcomas have been reported in Syrian (Mesocricetus auratus) and Siberian dwarf (Phodopus sungorus) hamsters but, to our knowledge, the current report represents the first case of histiocytic sarcoma described in an Armenian hamster. It is plausible to consider the animal's experimental immunization history and the development of the histiocytic sarcoma to be related. An association between adjuvanted vaccines and soft-tissue sarcomas has been described in cats and referred to as feline injection-site sarcomas.

Myocardial transcription of inflammatory and remodeling markers in cats with hypertrophic cardiomyopathy and systemic diseases associated with an inflammatory phenotype.

Feline hypertrophic cardiomyopathy (HCM) is characterized by macrophage-driven myocardial remodeling processes in a pro-inflammatory environment. To further investigate the mechanisms behind these processes, the myocardial transcription of cytokines and remodeling enzymes was comparatively assessed in cats with HCM and cats without cardiac diseases. Sixty-seven cats were included, 17 cats with HCM (including 5 with atrial thrombus; AT), and 50 cats without cardiac diseases. The latter comprised 10 control cats (no cardiac or relevant systemic disease), 34 cats with diseases suspected to be associated with a systemic inflammatory state of which 18 suffered from feline infectious peritonitis (FIP), and 6 cats with multicentric lymphoma. Samples from atria, ventricular free walls and interventricular septum were examined using quantitative reverse transcriptase PCR. The overall highest myocardial marker transcriptions were observed in cats with multicentric lymphoma, FIP and HCM, followed by diseases likely associated with a systemic inflammatory state, and control cats. Inflammatory marker transcription predominated in the myocardium of cats with systemic inflammatory diseases, whereas in HCM the transcription of remodeling enzymes prevailed. Sex significantly influenced the myocardial transcription of several remodeling enzymes. These results suggest a versatile myocardial response depending on the disease and illustrates the relevance of sex for the cardiac response to cardiac and systemic disease in cats. A systemic inflammatory state appears to elicit an inflammatory phenotype in the myocardium, whereas in HCM, the myocardium mediates its own remodeling. In HCM, the identified markers might be involved in the ongoing remodeling processes causing structural and functional changes.

A Novel Hybrid Membrane VAD as First Step Toward Hemocompatible Blood Propulsion.

Heart failure is a raising cause of mortality. Heart transplantation and ventricular assist device (VAD) support represent the only available lifelines for end stage disease. In the context of donor organ shortage, the future role of VAD as destination therapy is emerging. Yet, major drawbacks are connected to the long-term implantation of current devices. Poor VAD hemocompatibility exposes the patient to life-threatening events, including haemorrhagic syndromes and thrombosis. Here, we introduce a new concept of artificial support, the Hybrid Membrane VAD, as a first-of-its-kind pump prototype enabling physiological blood propulsion through the cyclic actuation of a hyperelastic membrane, enabling the protection from the thrombogenic interaction between blood and the implant materials. The centre of the luminal membrane surface displays a rationally-developed surface topography interfering with flow to support a living endothelium. The precast cell layer survives to a range of dynamically changing pump actuating conditions i.e., actuation frequency from 1 to 4 Hz, stroke volume from 12 to 30 mL, and support duration up to 313 min, which are tested both in vitro and in vivo, ensuring the full retention of tissue integrity and connectivity under challenging conditions. In summary, the presented results constitute a proof of principle for the Hybrid Membrane VAD concept and represent the basis for its future development towards clinical validation.

Canine Dilated Cardiomyopathy: Diffuse Remodeling, Focal Lesions, and the Involvement of Macrophages and New Vessel Formation.

Dilated cardiomyopathy (DCM) is among the most common cardiac diseases in dogs. Its pathogenesis is not fully understood, but myocardial remodeling and inflammation are suspected to be involved. The present study aimed to characterize the pathological processes in canine DCM, investigating morphological changes in association with the expression of relevant cytokines and remodeling markers. The myocardium of 17 dogs with DCM and 6 dogs without cardiac diseases was histologically evaluated, and selected cases were further examined by immunohistochemistry, morphometry, and reverse transcription quantitative PCR. In DCM, the myocardium exhibited subtle but statistically significant diffuse quantitative changes. These comprised increased interstitial collagen deposition and macrophage numbers, as well as an overall reduced proportion of contractile tissue. This was accompanied by a significant increase in myocardial transcription of intracellular adhesion molecule (ICAM) 1, inflammatory cytokines, and remodeling enzymes. Laser microdissection showed that cardiomyocytes transcribed most relevant markers including ICAM-1, tumor necrosis factor α, transforming growth factor ß (TGF-ß), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of MMP (TIMP) 1 and TIMP-2. In addition, there were multifocal cell-rich lesions characterized by fibrosis, neovascularization, macrophage infiltration, and cardiomyocyte degeneration. In these, macrophages were often found to express ICAM-1, TGF-ß, and vascular endothelial growth factor; the former two were also expressed by cardiomyocytes. These results characterize the diffuse myocardial remodeling processes that occur in DCM. The observed multifocal cell-rich lesions might result from reduced tissue perfusion. Macrophages and cardiomyocytes seem to actively contribute to the remodeling processes, which ultimately lead to cardiac dilation and dysfunction. The precise role of the involved cells and the factors initiating the remodeling process still needs to be identified.

Feline Hypertrophic Cardiomyopathy: The Consequence of Cardiomyocyte-Initiated and Macrophage-Driven Remodeling Processes?

vHypertrophic cardiomyopathy (HCM) is the most commonly diagnosed cardiac disease in cats. The complex pathophysiology of HCM is still far from clear, but myocardial remodeling is a key process, and cardiomyocyte disarray, interstitial fibrosis, leukocyte infiltration, and vascular dysplasia are described histopathologic features. The present study systematically investigated the pathological processes in HCM, with the aim to shed more light on its pathogenesis. Hearts from 18 HCM cases and 18 cats without cardiac disease (controls) were examined, using light and transmission electron microscopy, immunohistochemistry, and morphometric approaches to identify and quantify the morphological changes. Reverse transcription-quantitative polymerase chain reaction was applied to provide additional mechanistic data on remodeling processes. In HCM, the left and right ventricular free wall and septal myocardium exhibited a significantly reduced overall cellularity, accompanied by a significant increase in interstitial Iba1-positive cells with macrophage morphology. In addition, the myocardium of almost half of the diseased hearts exhibited areas where cardiomyocytes were replaced by cell-rich fibrous tissue with abundant small and medium-sized vessels. HCM hearts also showed significantly higher transcription levels for several inflammatory and profibrotic mediators. Our findings suggest that HCM is the consequence of cardiac remodeling processes that are the result of cardiomyocyte damage and to which macrophages contribute by maintaining an inflammatory and profibrotic environment.

Myocardial leptin transcription in feline hypertrophic cardiomyopathy.

Leptin is an adipokine, which is in humans with cardiac disease suspected to be involved in myocardial remodeling and thrombus formation. In cats, however, it is not known whether leptin plays a role in cardiac disease, i.e. hypertrophic cardiomyopathy (HCM) and the presence of an atrial thrombus (AT). The objective of the study was therefore to establish whether leptin is transcribed in the feline myocardium and to compare myocardial leptin mRNA concentrations in cats with HCM with and without AT, and in cats without cardiac diseases. Myocardial samples from 15 cats with HCM (five of these with AT), and 12 cats without cardiac diseases were investigated for leptin mRNA expression using quantitative reverse transcriptase PCR, and the transcription levels were correlated with those obtained for a range of cytokines and remodeling parameters. Leptin mRNA expression was detected in the myocardium in all heart regions, with generally higher concentrations in the atria than in the ventricles. Cats with HCM exhibited higher atria and ventricular leptin transcription than cats without cardiac diseases, but reduced ventricular transcription levels in the presence of AT. A positive correlation between leptin, cytokine and remodeling marker transcription levels was observed. The present study shows that leptin is constitutively transcribed in the feline myocardium. The observed increase in leptin mRNA concentrations in the myocardium from cats with HCM and the reduction when an AT is present suggests varying gene activation in different stages of the disease and a potential involvement of leptin in the feline cardiac remodeling process.