Influence of heart rate on right ventricular function assessed by right heart catheterization and echocardiography in healthy anesthetized dogs.

BACKGROUND: Right ventricular (RV) functional assessment has received considerable attention in veterinary medicine since various diseases, such as cardiovascular, respiratory, endocrine, and neoplastic disease, may affect RV function. Heart rate (HR) is an important factor that can influence RV function through changes in loading condition and contractility. However, no study has yet evaluated the association between HR and RV function in the same individuals. This study aimed to evaluate the influence of elevated HR on RV function using right heart catheterization and echocardiography, and investigate the association between right heart catheterization and echocardiographic indices. RESULTS: Right atrial pacing was performed in eight dogs at 120, 140, 160, and 180 bpm. With an increase in HR, the RV systolic volume, RV diastolic volume, and stroke volume significantly decreased; however, the cardiac output, end-systolic elastance (Ees), and effective arterial elastance (Ea) significantly increased. Significant changes were not observed in RV pressure and Ees/Ea. The RV area normalized by body weight, RV fractional area change normalized by body weight (RV FACn), and tricuspid annular plane systolic excursion normalized by body weight (TAPSEn) significantly decreased with increased HR. Peak systolic myocardial velocity of the lateral tricuspid annulus (RV s'), RV strain, and RV strain rate of only the RV free wall analysis (RV-SrL3seg) showed no significant changes with the increase in HR; however, there was an increase in the RV strain rate of the RV global analysis (RV-SrL6seg). Multiple regression analysis revealed that HR, RV FACn, and RV- SrL6seg had significant associations with the Ees, and the TAPSEn and RV-SrL3seg with Ees/Ea. CONCLUSIONS: Decreased venous return and shortened relaxation time decreased the RV FAC, TAPSE, RV s', and RV strain, and might underestimate the RV function. Ees increased with the increase in HR, reflecting the myocardial force-frequency relation; as a result, RV-SrL6seg could be a useful tool for Ees estimation. Additionally, the RV-SrL3seg could detect RV performance, reflecting the balance between RV contractility and RV afterload.

A case of juvenile form of dilated cardiomyopathy in a 6-month-old Shiba Inu dog.

A 6-month-old Shiba Inu dog was brought to the Veterinary Medical Teaching Hospital because of a cough, exercise intolerance, and pulmonary edema. The dog had a Levine 2/6 systolic murmur. Transthoracic echocardiography revealed left atrial and ventricular dilatation (left atrium to aortic ratio: 2.8), mitral and tricuspid valve regurgitation, and severe left ventricular myocardial hypokinesia (fractional shortening was 11.8%). Bubble contrast echocardiography did not reveal a congenital shunt; therefore, the dog was clinically diagnosed with early onset dilated cardiomyopathy. From the first visit, the dog was treated with pimobendan, taurine, torasemide, and isosorbide dinitrate. After 435 days, echocardiography revealed that systolic function had not improved. On Day 465, atrial fibrillation was confirmed via electrocardiogram, and treatment with diltiazem hydrochloride was initiated. The dog continued to appear clinically stable thereafter, until it died suddenly 1087 days after the initial visit. A postmortem histopathological examination identified severe enlargement of the left atrial and ventricular chambers as well as attenuated wavy fibers in the ventricular myocardium, which confirmed dilated cardiomyopathy in a juvenile. This is the first report of a juvenile form of dilated cardiomyopathy in a Shiba Inu dog. This case report provides evidence that the extended prognosis of this dog differed from that in previously reported cases of dilated cardiomyopathy in young dogs. Key clinical message: This is the first reported case of a juvenile form of dilated cardiomyopathy in a Shiba Inu dog. This report provides evidence that the prognosis of this dog differed from that in previously reported cases of dilated cardiomyopathy in young dogs.

Un cas de forme juvénile de cardiomyopathie dilatée chez un chien Shiba Inu de 6 mois. Un chien Shiba Inu de 6 mois a été amené à l'hôpital universitaire de médecine vétérinaire en raison d'une toux, d'une intolérance à l'exercice et d'un oedème pulmonaire. Le chien avait un souffle systolique Levine 2/6. L'échocardiographie transthoracique a révélé une dilatation auriculaire et ventriculaire gauche (rapport oreillette gauche sur aorte : 2,8), une régurgitation des valves mitrale et tricuspide et une hypokinésie myocardique ventriculaire gauche sévère (raccourcissement fractionnel de 11,8 %). L'échocardiographie de contraste par microbulles n'a pas révélé de shunt congénital; par conséquent, le chien a reçu un diagnostic clinique de cardiomyopathie dilatée d'apparition précoce. Dès la première visite, le chien a été traité avec du pimobendane, de la taurine, du torasémide et du dinitrate d'isosorbide. Après 435 jours, l'échocardiographie a révélé que la fonction systolique ne s'était pas améliorée. Au jour 465, la fibrillation auriculaire a été confirmée par électrocardiogramme et un traitement par le chlorhydrate de diltiazem a été instauré. Le chien a continué à apparaître cliniquement stable par la suite, jusqu'à ce qu'il meure subitement 1087 jours après la visite initiale. Un examen histopathologique post mortem a identifié une hypertrophie sévère des cavités auriculaire et ventriculaire gauche ainsi que des fibres ondulées atténuées dans le myocarde ventriculaire, ce qui a confirmé une cardiomyopathie dilatée chez un juvénile. Il s'agit du premier rapport d'une forme juvénile de cardiomyopathie dilatée chez un chien Shiba Inu. Ce rapport de cas fournit des preuves que le pronostic prolongé de ce chien différait de celui des cas précédemment rapportés de cardiomyopathie dilatée chez les jeunes chiens.Message clinique clé :Il s'agit du premier cas rapporté d'une forme juvénile de cardiomyopathie dilatée chez un chien Shiba Inu. Ce rapport fournit des preuves que le pronostic de ce chien différait de celui des cas précédemment rapportés de cardiomyopathie dilatée chez les jeunes chiens.(Traduit par Dr Serge Messier).

Early detection of myocardial dysfunction in a cat that gradually progressed to endomyocardial form of restrictive cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is a common myocardial disease in cats, characterized by diastolic dysfunction and atrial enlargement without myocardial hypertrophy. Especially, endomyocardial form of RCM, one of the subtypes in RCM, is characterized by endocardial fibrosis, endocardial scar bridging the interventricular septum and left ventricular (LV) free wall, and deformation and distortion of the LV. However, it is unclear how the myocardial dysfunction and the endocardial scar contribute to the pathophysiology of RCM disease progression. CASE PRESENTATION: A 3 years and 2 months old, intact male, Domestic shorthaired cat was presented for consultation of cardiac murmur. At the first visit (day 0), the notable abnormal finding was echocardiography-derived chordae tendineae-like structure bridging the interventricular septum and the LV free wall, resulting high-speed blood flow in the left ventricle. Electrocardiography, thoracic radiography and noninvasive blood pressure measurements were normal. No left atrial enlargement was observed, and LV inflow velocity showed an abnormal relaxation pattern. Although there was no abnormality in tissue Doppler imaging-derived myocardial velocity, two-dimensional speckle tracking echocardiography (2D-STE) revealed a decrease in the LV longitudinal strain and an increase in endocardial to epicardial ratio of the LV circumferential strain on day 0. On day 468, obvious left atrium enlargement and smoke like echo in the left atrium were observed. The LV inflow velocity was fused, and the tissue Doppler imaging-derived early-diastolic myocardial velocity of the septal mitral annulus decreased. Regarding 2D-STE, LV circumferential strain was further decreased, and right ventricular strain was additionally decreased. Although the general condition was good, we made a clinical diagnosis of endomyocardial RCM based on the above findings. On day 503, the cat showed the radiographic evidence of pulmonary edema and congestive heart failure signs. CONCLUSIONS: Cats with abnormal LV structure and associated myocardial dysfunction like this case needs careful observation. Additionally, 2D-STE indices may be useful for early detection of myocardial dysfunction in feline RCM.

A genetic variant of CYP2R1 identified in a cat with type 1B vitamin D-dependent rickets: a case report.

BACKGROUND: Vitamin D-dependent rickets is rare in animals and humans. Several types of this condition are associated with genetic variants related to vitamin D metabolism. This is the first report of type 1B vitamin D-dependent rickets in a cat. CASE PRESENTATION: Here, we describe the case of a 3-month-old female domestic short-haired cat previously fed on commercial kitten food that presented at our clinic with seizures, lethargy, and generalized pain. Serum and ionized calcium concentrations and 1,25-dihydroxycholecalciferol in this cat were low, and radiographs showed skeletal demineralization and abnormally wide growth plates on the long bones. Initially, simple vitamin D deficiency was suspected; however, the cat's profile, which included fed a well-balanced commercial diet, together with the findings of additional laboratory tests and the cat's unresponsiveness to various treatments, raised the suspicion of vitamin D-dependent rickets. Examination of the DNA sequences of CYP2R1 and CYP27B1 genes, which are genes linked with vitamin D metabolism, showed a CYP2R1 frameshift mutation in exon 5 (where T is deleted at position c.1386). This mutation alters the amino acid sequence from position 462, while the stop codon introduced at position 481 prematurely truncates the 501 amino acid full-length protein. With this knowledge, a new treatment regime based on a standard dose of calcitriol was started and this markedly improved the cat's condition. CONCLUSIONS: To the best of our knowledge, the present case is the first description of type 1B vitamin D-dependent rickets linked with a genetic variant of CYP2R1 in a cat.

Assessment of myocardial function in obstructive hypertrophic cardiomyopathy cats with and without response to medical treatment by carvedilol.

BACKGROUND: Inconsistency of treatment response in cats with obstructive hypertrophic cardiomyopathy is well recognized. We hypothesized that the difference in response to beta-blockers may be caused by myocardial functional abnormalities. This study was designed to compare myocardial function in cats with obstructive hypertrophic cardiomyopathy with and without response to beta-blockers. Twenty-one, client-owned, hypertrophic cardiomyopathy cats treated with carvedilol were analyzed. After carvedilol treatment, cats with decreased left ventricular outflow tract velocity were categorized as responders (n = 10); those exhibiting no response (no decrease in the left ventricular outflow tract velocity) were categorized as non-responders (n = 11). The cats were examined using layer-specific assessment of the myocardial function (whole, endocardial, and epicardial layers) longitudinally and circumferentially by two-dimensional speckle-tracking echocardiography, before and after carvedilol treatment. RESULTS: The non-responder cats had a significantly higher age, end-diastolic left ventricular posterior-wall thickness, peak velocity of left ventricular outflow tract, and dose of carvedilol than the responders (p = 0.04, p < 0.01, p < 0.01, and p < 0.01, respectively). The circumferential strain in the epicardial layer was lower and circumferential endocardial to epicardial strain ratio was higher in non-responders than responders (p < 0.001 and p = 0.006). According to the multivariate analysis, circumferential strain in the epicardial layer was the only independent correlate of treatment response with carvedilol. CONCLUSIONS: Myocardial function, assessed by two-dimensional speckle-tracking echocardiography, differed in cats with hypertrophic cardiomyopathy with and without response to beta-blockers. The determination of layer-specific myocardial function may facilitate detailed pathophysiologic assessment and treatment response in cats with hypertrophic cardiomyopathy.

Hepatocellular carcinoma in a young dog.

A 25-month-old Chihuahua dog with no clinical signs was evaluated for high serum liver enzymes. Ultrasonography and computed tomography revealed a mass in the left hepatic medial lobe. The histological diagnosis reached using resected tissues was hepatocellular carcinoma (HCC). To the authors' knowledge, this is the youngest dog diagnosed with HCC.

Carcinome hépatocellulaire chez un jeune chien. Un chien Chihuahua âgé de 25 mois qui ne présentait aucun signe clinique de maladie a été évalué pour des enzymes hépatiques sériques élevés. L'échographie et la tomodensitométrie ont révélé une masse dans le lobe hépatique médial gauche. Le diagnostic histologique obtenu à partir de tissus reséqués a été le carcinome hépatocellulaire (CHC). À la connaissance des auteurs, il s'agit du plus jeune chien diagnostiqué avec le CHC.(Traduit par Isabelle Vallières).

Prognostic value of pulmonary vascular resistance estimated by echocardiography in dogs with myxomatous mitral valve disease and pulmonary hypertension.

BACKGROUND: Progression to combined post- and pre-capillary pulmonary hypertension (PH) provides prognostic information in human patients with post-capillary PH. Pulmonary vascular resistance estimated by echocardiography (PVRecho) is useful for the stratification of dogs with myxomatous mitral valve disease (MMVD) and detectable tricuspid regurgitation. OBJECTIVES: To evaluate the prognostic value of PVRecho in dogs with MMVD. ANIMALS: Fifty-four dogs with MMVD and detectable tricuspid regurgitation. METHODS: Prospective cohort study. All dogs underwent echocardiography. The PVRecho was calculated based on tricuspid regurgitation and the velocity-time integral of the pulmonary artery flow. To evaluate the influence of echocardiographic variables on cardiac-related deaths, Cox proportional hazard analysis was performed. Additionally, Kaplan-Meier curves classified by PVRecho tertiles were made and compared using log-rank tests to evaluate the influence of PVRecho on all-cause mortality and cardiac-related death. RESULTS: The median follow-up time was 579 days. Forty-one dogs with MMVD (PH severity [number]: no or mild, 21/33; moderate, 11/11; severe, 9/10) died during the study. In the multivariable Cox proportional hazard analysis adjusted for age, sildenafil administration, and American College of Veterinary Internal Medicine stage of MMVD, left atrial to aortic diameter ratio and PVRecho remained significant (adjusted hazard ratio [95% confidence interval]: 1.2 [1.1-1.3] and 2.1 [1.6-3.0], respectively). Higher PVRecho showed a significant association with lower survival rates. CONCLUSIONS AND CLINICAL IMPORTANCE: Left atrial enlargement and high PVRecho were independent prognostic factors in dogs with MMVD and detectable tricuspid regurgitation.

Echocardiographic characteristics of dogs with pulmonary hypertension secondary to respiratory diseases.

BACKGROUND: Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right-sided heart failure. HYPOTHESIS/OBJECTIVES: To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases. ANIMALS: Thirty-one dogs with respiratory diseases with or without PH and 15 healthy dogs. METHODS: Prospective cross-sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH-relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH-relevant signs) was investigated. RESULTS: Twenty-one dogs were diagnosed with PH; of these, 11 showed PH-related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH-related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4-20.8] and 16.8 [15.3-29.5] mL/m2 , respectively). Dogs with RLD had higher echocardiography-estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9-3.3] and 1.6 [1.3-2.2], respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH-related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD.

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.

Beraprost Sodium for Pulmonary Hypertension in Dogs: Effect on Hemodynamics and Cardiac Function.

Pulmonary hypertension (PH) is a fatal condition that affects many dogs. In humans, PH is often treated with beraprost sodium (BPS). However, the effectiveness of BPS for canine PH has not been established. This study aimed to evaluate the clinical and cardiovascular response of BPS in canine patients with PH of various causes. Sixteen dogs with PH (post-capillary PH, n = 8; pre-capillary PH, n = 8) were included. BPS was continuously administered twice daily at 15 µg/kg. All dogs underwent echocardiography, including speckle-tracking analysis and blood pressure measurement, before and after BPS administration. Continuous BPS administration (range: 13.2-22.0 µg/kg) significantly decreased the pulmonary and systemic vascular impedance and increased left and right ventricular myocardial strain. In dogs with post-capillary PH, BPS administration caused no significant worsening of the left atrial pressure indicators. No side effects of BPS were observed in any dog. BPS also improved cardiac function and pulmonary circulation through pulmonary vasodilation, suggesting that BPS may be an additional treatment option for canine PH of various causes. Particularly, BPS increased left ventricular function and systemic circulation without worsening the left heart loading condition in dogs with post-capillary PH.

A Case of a Small-Breed Dog with Diet-Related Dilated Cardiomyopathy Showing Marked Improvements in Cardiac Morphology and Function after Dietary Modification.

An 11-year-old intact female Papillion weighing 2.1 kg was referred to our institution with the main complaint of shallow, rapid breathing. At the first visit (day 0), although clinical signs improved due to the use of medication from the primary hospital, transthoracic radiography and echocardiography revealed left heart enlargement and left ventricular dysfunction. A clinical diagnosis of dilated cardiomyopathy (DCM) was made and oral administration of pimobendan, temocapril, and taurine was initiated. However, on day 10, the respiratory status worsened and furosemide was prescribed. On day 54, no significant improvement in heart size was observed. Additionally, the diet that this patient received met the recommendation for diet-related DCM by the U.S. Food and Drug Administration, and the patient's diet was changed from a grain-free diet to a grain-containing diet. On day 1191, the patient's respiratory status was stable and no clinical signs were observed. Transthoracic radiography and echocardiography revealed an improvement in left heart size. Additionally, improvements in the left and right ventricular myocardial strains were observed after changing the diet. We suggest that it may be necessary to suspect a dietary association with dilated cardiomyopathy, and a good prognosis might be expected by dietary modification, even in small-breed dogs.

Utility of Real-Time Three-Dimensional Echocardiography for the Assessment of Right Ventricular Morphology and Function in Large Animal Models.

Real-time three-dimensional echocardiography (RT3DE) enables a noninvasive assessment of right ventricular (RV) morphology. However, no study has evaluated the relationship between RV function obtained by RT3DE and RV pressure-volume loops. This hypothesis-driven, experimental study aimed to assess the utility of RT3DE in the evaluation of RV morphology and function. Ten anesthetized beagle dogs sequentially underwent dobutamine infusion, acute infusion of lactated Ringer's solution, and furosemide administration to alter RV contractility and loading conditions. RV pressure-volume loop-derived hemodynamic measurements and echocardiography, including two-dimensional speckle-tracking echocardiography and RT3DE, were performed in each study protocol. Bland−Altman analysis showed strong agreement in RV volume, ejection fraction, and stroke volume obtained by right heart catheterization and RT3DE. Multiple regression analyses revealed that the peak myocardial velocity of the lateral tricuspid annulus (RV s') and global RV longitudinal strain rate were significantly associated with end-systolic elastance (adjusted r2 = 0.66, p < 0.001). RV s', RV free wall longitudinal strain, and RT3DE-derived stroke volume/end-systolic RV volume ratio were associated with RV pressure-volume loops-derived end-systolic/arterial elastance ratio (adjusted r2 = 0.34, p < 0.001). RT3DE could detect the changes in catheterization-derived RV volume with a strong agreement and might be useful in estimating RV-pulmonary arterial coupling.

Investigation of Beraprost Sodium on Cardiac Function and Hemodynamics in Canine Models of Chronic Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by increased pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. No study has evaluated the utility of Beraprost sodium (BPS) in dogs with PH. This study aimed to evaluate the effect of BPS on cardiac function and hemodynamics and examine the optimal dose of BPS in canine models of chronic embolic PH. In this prospective crossover study, three doses of BPS (5, 15, and 25 µg/kg, twice a day) were examined in eight canine models of chronic embolic PH. All model dogs underwent invasive PAP measurement, echocardiography, and non-invasive systemic blood pressure measurement before and after continuous administration of oral BPS for 1 week. No side effects of BPS were observed in any dog during the study. All doses of BPS significantly decreased systolic PAP and pulmonary vascular impedance. Additionally, systemic vascular impedance significantly decreased with 15 and 25 µg/kg of BPS. The right ventricular stroke volume and longitudinal strain significantly decreased with all doses of BPS. The left ventricular stroke volume and circumferential strain decreased with 15 µg/kg BPS. BPS was well-tolerated in this study. A dose-dependent vasodilating effect on pulmonary vessels was observed in canine models of chronic PH. Additionally, 15 µg/kg BPS showed a balanced vasodilating effect on systemic and pulmonary vessels. Furthermore, with a decrease in systemic and pulmonary vascular impedance, the left and right ventricular functions were significantly improved. Our results suggest that BPS may be useful in the treatment of canine PH.

Effects of transforming growth factor-ß3 and matrix metalloproteinase-3 on the pathogenesis of chronic mitral valvular disease in dogs.

OBJECTIVE: To investigate the roles of transforming growth factor-ß (TGF-ß) isoforms and matrix metalloproteinases (MMPs) in development of chronic mitral valvular disease (CMVD) in dogs. SAMPLE POPULATION: 12 mitral valve leaflets collected from cadavers of 5 clinically normal dogs and from 7 dogs with CMVD. PROCEDURES: Expression of TGF-ß isoforms 1, 2, and 3; MMPs 1, 2, 3, and 9; TGF-ß receptor II (TßR-II); and α smooth muscle actin (αSMA) in mitral valves of dogs with CMVD was compared with that in mitral valves from clinically normal dogs. Additionally, responses of valvular interstitial cells (VICs) to TGF-ß3, MMP-3, and angiotensin-converting enzyme inhibitor (ACEI) as a suppressor of TGF-ß3 were examined in vitro. RESULTS: Expression of TGF-ß3, TßR-II, αSMA, and MMP-3 was only detected in mitral valves of dogs with CMVD. Concentrations of αSMA and proteoglycans in cultured VICs were significantly increased following incubation with TGF-ß3; treatment with MMP-3 resulted in increased amounts of active and total TGF-ß3, and total TGF-ß3 in VICs was significantly decreased by incubation with ACEI. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that increased TGF-ß3 and MMP-3 contribute to the pathogenesis of valvular degeneration associated with CMVD. In addition, it is possible that the use of ACEI could effectively block pathological alterations in VICs associated with CMVD in vitro. Impact on Human Medicine-CMVD is associated with primary mitral valve prolapse and Marfan syndrome in humans. Results of the study reported here will help to elucidate the molecular mechanisms of CMVD in dogs and humans.

Right ventricular systolic and diastolic function assessed by two-dimensional speckle tracking echocardiography in dogs with myxomatous mitral valve disease.

Pulmonary hypertension (PH) is a common comorbidity in dogs with myxomatous mitral valve disease (MMVD), and can induce various changes in the right heart, such as right ventricular (RV) hypertrophy, dilatation, and dysfunction. We hypothesized that RV function, not only systolic function but also diastolic function, could be worsened with PH progression. We aimed to compare RV systolic and diastolic function in dogs with MMVD. Twenty healthy dogs and sixty-eight dogs with MMVD were enrolled. Dogs with MMVD were classified into the probability of PH. Two-dimensional and Doppler echocardiographic indices for right heart and two-dimensional speckle tracking echocardiography indices were measured. The morphological indicators of the right heart were significantly higher only in the high probability of PH group. The RV strain, early-diastolic and systolic strain rates were significantly lower in the high probability of PH group than those in the low and intermediate probability of PH groups. Multivariate analysis showed that increased RV internal dimension normalized by body weight and RV myocardial performance index were significantly associated with the presence of right-sided congestive heart failure. Speckle tracking echocardiography-derived RV systolic and diastolic function were activated in the low and intermediate probability of PH groups. However, dogs with high probability of PH showed RV myocardial dysfunction and dilatation. Increased RV myocardial performance index and end-diastolic RV internal dimension normalized by body weight were significantly associated with the presence of right-sided congestive heart failure in dogs with MMVD.

Immunomodulatory Effects of Canine Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles on Stimulated CD4+ T Cells Isolated from Peripheral Blood Mononuclear Cells.

Adipose tissue-derived mesenchymal stem cells (ADSCs) have anti-inflammatory and immunomodulatory characteristics. Many studies have suggested that the immunomodulation of ADSCs is largely mediated by secreted paracrine factors. Various factors are secreted from ADSCs, among which extracellular vesicles are considered to play a major role in the communication between ADSCs and target cells. Several studies have reported the function of canine ADSC-derived extracellular vesicles (cADSC-EVs), but few studies have reported the immunomodulatory effects of cADSC-EVs on immune cells. The purpose of this study was to investigate the effects of cADSC-EVs on in vitro-stimulated CD4+ T cells isolated from peripheral blood mononuclear cells (PBMCs). cADSC-EVs were isolated from cADSCs under naive conditions or primed conditions by tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). The expression levels of several microRNAs in cADSC-EVs were altered by priming with TNFα and IFNγ. Culturing PBMCs stimulated with concanavalin A in the presence of naive or primed cADSC-EVs inhibited the differentiation of PBMCs and CD4+ T cells and promoted apoptosis of PBMCs. CD4+, CD8+, and CD4+CD8+ T cells were decreased, while CD3+CD4-CD8- T cells were increased. T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells were analyzed by flow cytometry. cADSC-EVs inhibited the proliferation of Th1 and Th17 cells and enhanced Th2 and Treg cell proliferation. However, CD4+ T cells that had incorporated labeled cADSC-EVs comprised only a few percent of all cells. Therefore, these responses of stimulated CD4+ T cells may be due to not only direct effects of cADSC-EVs but also to indirect effects through interactions between cADSC-EVs and other immune cells. In conclusion, cADSC-EVs exert immunosuppressive effects on stimulated CD4+ T cells in vitro. These findings may be useful for further studies of immune diseases.

Investigation of the influence of manual ventilation-controlled respiration on right ventricular pressure-volume loops and echocardiographic variables in healthy anesthetized dogs.

OBJECTIVE: To evaluate the influence of manual ventilation-controlled respiration on right ventricular (RV) pressure-volume loop-derived and echocardiographic variables in dogs. ANIMALS: 8 healthy, anesthetized Beagles. PROCEDURES: In a prospective experimental study, pressure-volume catheters were percutaneously inserted into the right ventricle of each dog, and manual ventilation was performed; RV pressure-volume loop (hemodynamic) data and conventional echocardiographic variables were assessed. Two-dimensional speckle tracking echocardiography-derived RV strain (RVS) and RV systolic strain rate (RVSR) were obtained with RV free wall-only analysis (free wall) and RV global analysis (RVGA; interventricular septum). Variables were compared between end-inspiratory and end-expiratory phases of respiration by statistical methods. Multiple regression analysis was used to assess associations between selected hemodynamic and echocardiographic variables. RESULTS: The RV pressure significantly increased, and RV volume, stroke volume, tricuspid annular plane systolic excursion, RV fractional area change, peak myocardial systolic velocity of the lateral tricuspid annulus, and RV free wall only-assessed RVS and RVSR significantly decreased in the inspiratory phase, compared with the expiratory phase. There were no significant differences in end-systolic elastance or RVGA-assessed RVS or RVSR between respiratory phases. The RVGA-assessed RVSR was significantly associated with stroke volume and end-systolic elastance. CONCLUSIONS AND CLINICAL RELEVANCE: Specific RV echocardiographic variables were significantly affected by respiration. In contrast, RVS and RVSR determined with RVGA were not affected by respiration and were associated with hemodynamic indicators of RV contractility.

Utility of tricuspid annular plane systolic excursion normalized by right ventricular size indices in dogs with postcapillary pulmonary hypertension.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) is a common right ventricular (RV) function indicator. However, TAPSE was not decreased in dogs with myxomatous mitral valve disease (MMVD) and postcapillary pulmonary hypertension (PH) because of its load, angle, and body weight dependency, and TAPSE was considered a preload-dependent index. OBJECTIVES: To evaluate the utility of TAPSE normalized by RV size in dogs with postcapillary PH. ANIMALS: Twenty healthy dogs and 71 MMVD dogs with or without PH. METHODS: In this prospective observational study, end-diastolic RV internal dimension (RVIDd), end-diastolic and end-systolic RV area, and end-diastolic RV wall thickness were measured as RV size indices. The TAPSE was measured using B-mode and M-mode methods. Normalized TAPSE was calculated by dividing TAPSE by each RV size index. The RV strain was obtained as the detailed RV function using 2-dimensional speckle tracking echocardiography. All indices were compared among the PH severity groups and in the presence of right-sided congestive heart failure (R-CHF). RESULTS: Although nonnormalized TAPSE was higher with PH severity progression, each normalized TAPSE showed a significant decrease in the severe PH group (P < .05). The TAPSEB-mode /RVIDd ratio had high area under the curve to predict R-CHF and had moderate correlation with RV strain (P < .05). The TAPSEB-mode /RVIDd and left atrial-to-aortic diameter ratios were independent predictors for R-CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Normalized TAPSE could reflect RV systolic dysfunction in dogs with severe PH, which could not be detected by nonnormalized TAPSE. The TAPSEB-mode /RVIDd ratio might predict R-CHF with high sensitivity and reproducibility.

Left and Right Myocardial Functionality Assessed by Two-Dimensional Speckle-Tracking Echocardiography in Cats with Restrictive Cardiomyopathy.

The endomyocardial form of restrictive cardiomyopathy (EMF-RCM), a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with EMF-RCM, causing this disease pathophysiology and clinical status. Out of the 25 animals included in this study, 10 were client-owned cats with EMF-RCM, and 15 were healthy cats. In this study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography (2D-STE). Cats with EMF-RCM had depressed left ventricular myocardial deformations both in systole (whole longitudinal strain, epicardial longitudinal strain, and endocardial circumferential strain) and diastole (early and late diastolic longitudinal strain rates, and late diastolic circumferential strain rate) compared to controls. Furthermore, some right ventricular myocardial deformations (systolic longitudinal strain in epicardial layers, and endocardial-to-epicardial strain ratio) were significantly differerent in cats with EMF-RCM. Myocardial function assessed by 2D-STE could reveal left and right myocardial dysfunction.

Pulmonary Vascular Resistance Estimated by Echocardiography in Dogs With Myxomatous Mitral Valve Disease and Pulmonary Hypertension Probability.

Post-capillary pulmonary hypertension (PH) is a life-threatening complication in dogs with myxomatous mitral valve disease (MMVD). An increase in pulmonary vascular resistance (PVR) is associated with post-capillary PH progression. In humans, PVR estimated by echocardiography (PVRecho) enables the non-invasive assessment of PVR in patients with PH. This study aimed to evaluate the clinical utility of PVRecho in dogs with MMVD, PH probability, and right-sided congestive heart failure (R-CHF). Dogs with MMVD and detectable tricuspid valve regurgitation were included in the study. Dogs were classified into three PH probability groups (low/intermediate/high) and according to the presence or absence of R-CHF. All dogs underwent echocardiographic measurements for right ventricular (RV) morphology and function. PVRecho was calculated by two methods using tricuspid valve regurgitation velocity and velocity-time integral of the pulmonary artery flow (PVRecho and PVRecho2). RV size indicators were significantly higher with a higher probability of PH. RV strain and velocity-time integral of the pulmonary artery flow in the high probability group were significantly lower than those in the other groups. Tricuspid valve regurgitation velocity, PVRecho, and PVRecho2 were significantly higher with an increase in PH probability. Logistic regression analysis revealed a significant association between the presence of R-CHF and increased PVRecho2 and end-diastolic RV internal dimension normalized by body weight. PVRecho and PVRecho2 showed significant differences among the PH probability groups. These non-invasive variables may be useful for the diagnosis and stratification of PH and the determination of the presence of R-CHF in dogs with MMVD.