Pathological features of primary cardiac myxoid tumour in dogs: a review of 11 cases (2002-2022).

This report documents the pathological features of primary cardiac myxoid tumour (MT) in 11 dogs. Macroscopically, all the tumours were located in the tricuspid valve (TV), its septal leaflet being predominantly affected. Therefore, it appears that the TV is the most common site of occurrence for cardiac MT in dogs. Two gross anatomical types of canine valvular MT were evident. Seven of the 11 tumours were round or oval with a smooth or gently lobulated and glistening surface, while the other four were gelatinous, multilobulated and polypoid, with an irregular surface. Microscopically, in nine cases the tumours had an abundant myxoid matrix within which elongated spindle-shaped cells with no remarkable cytological atypia were sparsely embedded, suggesting a benign character (ie, myxoma). In the other two cases the tumours consisted of variably dense, haphazardly arranged, interlacing streams of anaplastic spindle-shaped or polygonal cells containing many mitotic figures, indicative of a malignant form of myxoma (ie, myxosarcoma). Isolated or clustered collections of myxoma cells (eg, cords, rings, syncytia) characteristic of human atrial myxoma were only rarely evident or lacking in all 11 cases, indicating that rarity or absence of such structural features may be specific to valvular MTs. Immunohistochemical findings were indicative of smooth muscle differentiation of the neoplastic cells. Tumour embolization to the intrapulmonary arteries and/or tumour implantation on the endocardium of the right heart chambers was evident only in the four cases of irregular-surfaced MT.

The anatomical basis of third-degree atrioventricular block in dogs with atrioventricular valve endocardiosis.

The cardiac conduction system was examined histologically in 13 canine cases of atrioventricular (AV) valve endocardiosis with third-degree AV block. In all cases, gross examination revealed marked thickening and distortion of the base of the central fibrous body (CFB) and varying degrees of endocardial thickening of the upper portion of the ventricular septum (VS) as well as marked thickening of the mitral and tricuspid valve leaflets due to myxomatous degeneration. Microscopically, the thickened and distorted CFB had encased or trapped, either partly or totally, the underlying penetrating and branching portions of the AV bundle. The myxomatous and/or fibrofatty tissue, which had proliferated at the base of the extensive CFB, protruded into or encroached on the AV bundle, causing severe (51-75%) to very severe (76% or more) reduction of the conduction fibres. The upper portions of the left and right bundle branches were involved in the endocardial thickening due to degenerative and fibrotic changes at the uppermost VS; however, both bundle branches were much less severely affected than the AV bundle, the degree of reduction of the conduction fibres ranging from mild (25% or less) to moderate (26-50%). These observations suggest that the sites most vulnerable to lesions in the AV conduction system are the penetrating and branching portions of the AV bundle, which would represent the anatomical basis for third-degree AV block in canine cases of AV valve endocardiosis.

Cardiac Inflammatory Myofibroblastic Tumours in Three Young Adult Cats.

Inflammatory myofibroblastic tumours (IMTs) of the heart are described in three young adult cats (case 1, 3.5 years old; case 2, 2.7 years old; case 3, 1.8 years old) that died due to pleural and pericardial effusions resulting from congestive heart failure. At necropsy, cardiac masses, measuring 4 × 3 × 2.5 cm (case 1), 3.5 × 2.5 × 2 cm (case 2) and 3 × 2.5 × 2 cm (case 3), were located mainly in the right auricle (case 1) and atrial septum (cases 2 and 3) with variable extension into the surrounding tissue. Histologically, the atrial masses in all three cats comprised proliferation of spindloid mesenchymal cells and an inflammatory infiltrate of plasma cells and lymphocytes in variable amounts of myxoid background. The spindloid cells were uniform and characterized by pale eosinophilic cytoplasm and a vesicular nucleus containing prominent nucleoli, with no remarkable cytological atypia or mitotic activity. Immunohistochemically, these cells were positive for vimentin and α-smooth muscle actin in all cases, supporting a myofibroblastic origin. The histopathological and immunohistochemical features were consistent with those of IMTs in humans and animals. There have been no previous reports of such tumours occurring in the heart of the cat.

Histological Features of the Atrioventricular Conduction System in Cats with High-Grade Atrioventricular Block.

The histopathological features of the atrioventricular (AV) conduction system of nine cats with high-grade atrioventricular block (H-AVB) were compared with those of 22 cases of third-degree atrioventricular block (3-AVB). All nine H-AVB cats had experienced syncopal attacks of variable severity and had been diagnosed electrocardiographically. The AVB, which was permanent in all cases, had been observed for 15-1,981 days (average 663 days) before death. Histological examination of the AV conduction system revealed moderate (25-50%) or severe (>50%) loss of conduction fibres associated with fibrous replacement in the regions of the branching portion of the AV bundle and the upper portion of the left bundle branch in almost all of the H-AVB cases and in all the 3-AVB cases. Comparison of lesion severity in each region in the H-AVB and 3-AVB cases revealed that the branching portion of the AV bundle was less severely affected in the H-AVB cases. This finding might explain why the H-AVB cases had intermittent block of AV conduction while the 3-AVB cats had permanent block.

Glycogen storage disease in a young cat with heart failure.

An 8-month-old domestic short-haired female cat presented with acute tachypnea, poor growth, hypothermia, and lethargy. Thoracic radiography showed cardiomegaly with mild pleural effusion, and transthoracic echocardiography identified dilatation of both atria and left ventricular systolic dysfunction. Although clinical signs improved temporarily with treatment, the cat died of pulmonary edema 135 days after the first visit. At necropsy, the heart was grossly enlarged. Microscopic examination of the heart identified severe vacuolization of cardiac muscle cells in histologic sections stained with hematoxylin and eosin. Examination of periodic acid-Schiff stained preparations of formalin-fixed heart tissue disclosed coarse granules within vacuoles that disappeared on predigestion with diastase, indicating that they were glycogen. On the basis of these findings, a necropsy diagnosis of glycogen storage disease type II (Pompe disease) was made. This report is the first case of a young cat with clinical signs closely resembling infantile Pompe disease of humans.

Clinical and necropsy evaluation of endocardial fibroelastosis in a mixed-breed cat with left side heart failure.

A two-month-old, male intact, mixed-breed cat weighing 0.6 kg was presented with respiratory distress and anorexia. From the transthoracic echocardiographic, reduced fractional shortening (FS) and increased endocardial echogenicity were recognised with severe congestive heart failure (CHF). The kitten was administered an antibiotic and pimobendane under oxygen supplementation in an ICU cage. However, the respiratory condition worsened and the cat died the next day, and the subsequent necropsy and histopathology examinations confirmed endocardial fibroelastosis (EFE). There is a lack of information regarding the antemortem cardiac function evaluated by tissue Doppler imaging (TDI) in EFE cases. We report on the echocardiographic findings including the TDI in the EFE cat with a concomitant necropsy and histopathology confirmation in this paper. The echocardiographic findings showed presence of a ventricular false tendon within the left ventricle, a decrease in the left ventricular contractility (FS 11.1%, and a marked CHF). In this case, the echocardiographic findings were consistent with the human counterpart. However, these findings were like those of dilated cardiomyopathy and, hence, non-specific to EFE. As a result, veterinarians should keep in mind that endocardial fibroelastosis might be a possible reason for respiratory distress resulting from CHF with a low fractional shortening in young cats.

The Anatomical Substrate for Sick Sinus Syndrome in Dogs.

The hearts of 28 dogs, clinically diagnosed as having symptomatic sick sinus syndrome (SSS), were examined post mortem, with a particular focus on the sinus node (SN) region. The affected dogs were divided into two groups according to the findings of ambulatory electrocardiography: 16 dogs with severe sinoatrial (SA) block and/or sinus arrest (group A) and 12 dogs with long sinus or atrial pauses due to SA block and/or sinus arrest accompanied by atrial tachyarrhythmias (group B). The most significant histopathological changes found in both SSS groups were extensive destruction of the SN characterized by depletion of nodal cells with fatty or fibrofatty replacement and interruption of contiguity between the SN and the surrounding atrial myocardium. Furthermore, in group B, the SN lesions were combined with fibrosis of the atrial myocardium. The results of this investigation improve our understanding of the close relationship between the electrocardiogram findings and pathological alterations in each group. Because most human cases of SSS are due to degenerative fibrosis of the SN, the loss and disappearance of nodal cells with a corresponding increase in fatty or fibrofatty tissue, may be specific to canine cases of SSS.

Pathological Features of Persistent Atrial Standstill Syndrome in Three Dogs.

The hearts of three dogs, clinically diagnosed as having persistent atrial standstill syndrome (PAS), were studied post mortem. The most significant gross findings in the hearts of all three dogs were dilatation and marked reduction in the thickness of both atrial walls. Histopathologically, all three had widespread progressive loss of the atrial myocardium with replacement by fatty or fibrofatty tissue, consistent with atrial myopathy. The lesion mainly affected the upper half of both atria and was more severe in the epimyocardium and midmyocardium than in the endomyocardium. On the basis of these observations, it is proposed that the atrial myopathy commences in the upper regions of both atria and progresses downwards, as has been demonstrated electrophysiologically in PAS in humans, and extends from the epicardium towards the endocardium.

Pathology and Proteomics-Based Diagnosis of Localized Light-Chain Amyloidosis in Dogs and Cats.

Amyloidosis is classified according to the amyloid precursor protein, and accurate diagnosis of the amyloidosis type may guide appropriate treatment. Immunohistochemistry and Congo red staining are the most frequently used methods used to distinguish types of amyloidosis, but problems with specificity and sensitivity indicate the need for an alternative diagnostic method. In this study, we evaluated laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) for the diagnosis of amyloid light-chain (AL) amyloidosis in animals. Plasmacytomas with amyloid deposits from 15 dogs and 2 cats were subjected to Congo red staining with or without potassium permanganate pretreatment, immunohistochemistry for kappa and lambda light chains, and LMD-LC-MS/MS. Congo red staining was diagnostic in 12 of 17 cases based on resistance to potassium permanganate pretreatment, but in 5 of 17 cases the pretreatment unexpectedly reduced Congo red staining or abrogated the birefringence and a definitive diagnosis could not be reached. Immunohistochemistry detected kappa or lambda light chains in 6 of 17 cases. With LMD-LC-MS/MS, immunoglobulin lambda light chain was detected in all 17 cases. The amyloid signature proteins ApoA-I, ApoA-IV, and ApoE were detected in 9, 1, and 3 of the 15 canine cases by LMD-LC-MS/MS, but not in the feline cases. In conclusion, LMD-LC-MS/MS consistently determined the amyloid type in all examined specimens, while Congo red staining after potassium permanganate treatment and immunohistochemistry were less sensitive tests.

Increased proportion of apoptotic cells in cat kidney tissues infected with feline morbillivirus.

In order to study potential pathogenic mechanisms of feline morbillivirus (FeMV) in infected kidney cells, we performed a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and an immunofluorescence assay (IFA) with an anti-FeMV P protein antibody on a total of 38 cat kidney tissues, 12 of which were positive for FeMV. Among these samples, we detected significantly larger numbers of apoptotic cells in FeMV-positive tissues than in FeMV-negative tissues, and in these tissues, a substantial percentage of TUNEL-positive (TUNEL+) cells contained the FeMV P protein (mean, 37.4; range, 17.4-82.9), suggesting that induction of apoptosis may be an important mechanism for pathological changes associated with FeMV infection in cat kidney tissues.

Invasion of Pheochromocytoma from the Caudal Vena Cava to the Right Ventricular Cavity in a Dog.

Pheochromocytomas are catecholamine-secreting tumors that are composed of neuroectoderm-derived chromaffin cells. An 8-year-old miniature dachshund with abdominal distension was diagnosed with a neuroendocrine tumor with invasion from the caudal vena cava to the right ventricular cavity. The dog died due to hypotensive shock from the vagal reflex, and on autopsy, an extra-adrenal pheochromocytoma (paraganglioma) was diagnosed in the caudal abdomen. At autopsy, the tumor plug of the caudal vena cava was confirmed. To the best of our knowledge, this is the first case report that echo-captured the extension of pheochromocytoma in the right ventricle and shows it in a figure and video file.

Long-term management of high-grade atrioventricular block using cilostazol in a cat.

CASE SUMMARY: A 12-year-old neutered female domestic shorthair cat was admitted for syncope. Clinical signs and electrocardiography revealed high-grade atrioventricular (AV) block. Treatment with cilostazol ameliorated the clinical signs and arrhythmia. However, the high-grade AV block recurred on several occasions. After 640 days, the cat presented again with clinical deterioration owing to reoccurrence of the arrhythmia and it died 11 days later. Histopathological examination revealed a loss of conduction cells within the His bundle. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of high-grade AV block treated with cilostazol in a cat. Treatment with cilostazol prolonged survival for 650 days without pacemaker implantation. Histological findings suggested that the AV block was related to fibrosis of the impulse conduction system.

Changes in copper, zinc and cadmium distributions in the liver of Formosan squirrels with characteristic high copper accumulation.

We discovered previously that Formosan squirrels (Callosciurus erythraeus) accumulate copper (Cu) in their livers at levels averaging 1700 µg per dry g (approximately 420 µg per wet g). In the current study, we investigated the relationship between Cu accumulation and hepatic injury, and we determined the distribution and chemical form of Cu in the liver supernatant. In particular, we explored the role of metallothionein in the liver supernatant. We observed no significant differences in hepatic Cu concentration between squirrels that showed pathological changes in the liver and those that did not. Serum alanine aminotransferase activity did not increase with increasing hepatic Cu concentration. These results suggest that abnormal Cu accumulation in the livers of Formosan squirrels does not induce severe hepatic injury. We found that 26.7% of the Cu in the liver was distributed to the supernatant, and only 11.0% of the Cu in the liver was bound to metallothionein, suggesting that metallothionein in the hepatic supernatant does not contribute to detoxification of excess Cu in Formosan squirrels.

Long-term outcomes of 54 dogs with tracheal collapse treated with a continuous extraluminal tracheal prosthesis.

OBJECTIVE: To describe the surgical placement of a continuous extraluminal tracheal prosthesis (CETP) and report the subsequent postoperative clinical outcomes in dogs with tracheal collapse. STUDY DESIGN: Retrospective case series. ANIMALS: Fifty-four dogs. METHODS: Medical records of dogs in which cervical and/or thoracic inlet tracheal collapse was diagnosed and treated by placement of a CETP between 2010 and 2017 were reviewed to evaluate postoperative complications, changes in respiratory function, and survival. Histological examinations of tracheal tissues performed in 2 dogs at 51 and 57 months after surgery were also reviewed. RESULTS: Fifty-three (98%) dogs survived to discharge. Postoperative complications included laryngeal paralysis (1 dog), disseminated intravascular coagulation (1 dog), and recurrent tracheal collapse (2 dogs). None of the dogs exhibited clinical evidence of tracheal necrosis. Preoperative dry, harsh cough resolved in 87% of the dogs after surgery. Goose honking cough was resolved in 25 of 26 (96%) dogs. Median follow-up time was 30 months (range, 16 days to 76 months). The survival rate at 36 months was 86% (CI: 75%-96%). On histological examination in 2 dogs, the tracheal tissue surrounding the prosthesis was well preserved and without evidence of chronic inflammation. CONCLUSION: Continuous extraluminal tracheal prosthesis placement in dogs with tracheal collapse resulted in low postoperative complication rates and good long-term outcomes. CLINICAL SIGNIFICANCE: Continuous extraluminal tracheal prosthesis placement provides a viable alternative surgical option for managing dogs with tracheal collapse.

Association of feline morbillivirus infection with defined pathological changes in cat kidney tissues.

Feline morbillivirus (FeMV) is an emerging member of morbillivirus discovered in 2012. Although association of FeMV infection with kidney diseases in cats has been suggested, the pathogenicity of the virus has not been clear to date. To study the association between FeMV infection and pathological changes in kidney tissues of infected cats, we performed immunohistochemistry and immunofluorescent assays to detect FeMV antigens and analyzed the effect of FeMV infection on the pathological changes in the kidney tissues. In 38 kidney tissue samples from cats, some tissue injury scores were significantly higher when the FeMV antigens were detected, especially those for the tubular tissues in which the FeMV antigens were mostly localized. Pathological changes associated with the FeMV antigens included the ones typically found in chronic kidney diseases, such as interstitial cell infiltration, glomerulosclerosis, tubular atrophy and fibrosis. We also detected some feline IgG localizations in glomerular tissues, though co-localization or significant association with the FeMV antigens were not found. Our study confirms the association of FeMV infection with some kidney tissue injuries and provides additional information about roles of FeMV infection in chronic kidney diseases.

Primary cardiac lymphoma in a 10-week-old dog.

A 10-week-old miniature dachshund presented with acute onset of weakness. Electrocardiography showed sustained ventricular tachycardia, and thoracic and abdominal radiography revealed pleural and peritoneal effusion. Echocardiography revealed severely hypokinetic left and right ventricles. Thoracocentesis and abdominocentesis and subsequent transfer to an oxygen chamber yielded no clinical improvement, and the dog died about 1 hr after admission. Gross examination of a longitudinal section through the entire heart revealed poorly demarcated focal or patchy areas of grayish-white tissue infiltrating extensively into the myocardium. Histologically, these lesions were consistent with infiltrative proliferation of neoplastic lymphoid cells. Immunohistochemical staining confirmed the diagnosis of primary cardiac lymphoma (PCL) of T-cell origin. There have been no previous reports of such young dogs with PCL.

Canine case of swallowing syncope that improved after pacemaker implantation.

A 14-year-old intact male West Highland White Terrier weighing 6.9 kg was admitted to the Tokyo University of Agriculture and Technology Animal Medical Center with the complaint of syncope after showing signs of nausea during feeding. Sinus arrest induced by deglutition was confirmed using a Holter electrocardiography test. However, the clinical symptoms significantly improved after implantation of a permanent pacemaker. Seven months after implantation, the dog died from acute pancreatitis, a cause unrelated to the syncope. Immediately after its death, the heart, lungs, gastrointestinal tract, and other organs were dissected and examined histopathologically. The brain was also examined using magnetic resonance imaging. Examination results led to the diagnosis of swallowing-induced situational syncope.

Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance.

Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+ sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+ sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21 in vivo and the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21 transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21 results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylation-dependent regulation. NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects of hHS-M21 on cardiac function. Elevation of hHS-M21 induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.

Evaluation of endothelialization in the center part of graft using 3 cm vascular grafts implanted in the abdominal aortae of the rat.

In order to develop small-diameter vascular grafts, it is necessary to evaluate endothelialization, especially, in the center part at early stage. For implantation of vascular grafts of 1 cm in length to abdominal aortae of rat, endothelial cells can be formed easily by stretching anastomosis. We evaluated the endothelialization in the center part of vascular grafts by implanting vascular grafts using transgenic (TG) silk fibroin (SF) of 3 cm in length. Vascular grafts were prepared 1.5 mm in diameter and 1 and 3 cm in length using wild type (WT) SF and TG SF by braiding structure, respectively. The grafts were removed after 2 weeks or 3 months and evaluated pathologically. Endothelialization was not confirmed totally after 3 months of implantation. However, endothelialization in the center part of grafts was significantly higher in TG SF than in WT SF. No significant difference was found regarding tissue infiltration and internal diameter. The TG SF revealed migration of the endothelial cells into the center part of the vessels at the early stage. Also, tissue infiltration and remodeling is expected using SF. The 3 cm length vascular grafts can be evaluated as a new experimental system.

Comparison of preventive effect of sildenafil and therapeutic effect of sildenafil treatment in rats with monocrotaline-induced pulmonary arterial hypertension.

This study aimed to investigate the potential effects of sildenafil on pulmonary hypertension (PH) in the monocrotaline (MCT)-induced PH rat. Twenty-four, 12-week-old, male Sprague-Dawley rats were injected with MCT or saline solution. After injection of MCT, rats received oral sildenafil immediately (early-phase treatment group: E group), 4 weeks after injection (late-phase treatment group: L group) or no treatment (MCT group) until 6 weeks after injection. Serial echocardiography and right ventricular systolic pressure (RVSP) measurements via a cardiac catheter were performed. RVSP was reduced in the E and L groups compared with the MCT group. Echocardiography indicated that sildenafil therapy prevents an increase in RVSP and preserves diastolic function, and this effect is not dependent on timing of initiation of therapy.