Progressive cardiomyopathy with intercalated disc disorganization in a rat model of Becker dystrophy.

Becker muscular dystrophy (BMD) is an X-linked disorder due to in-frame mutations in the DMD gene, leading to a less abundant and truncated dystrophin. BMD is less common and severe than Duchenne muscular dystrophy (DMD) as well as less investigated. To accelerate the search for innovative treatments, we developed a rat model of BMD by deleting the exons 45-47 of the Dmd gene. Here, we report a functional and histopathological evaluation of these rats during their first year of life, compared to DMD and control littermates. BMD rats exhibit moderate damage to locomotor and diaphragmatic muscles but suffer from a progressive cardiomyopathy. Single nuclei RNA-seq analysis of cardiac samples revealed shared transcriptomic abnormalities in BMD and DMD rats and highlighted an altered end-addressing of TMEM65 and Connexin-43 at the intercalated disc, along with electrocardiographic abnormalities. Our study documents the natural history of a translational preclinical model of BMD and reports a cellular mechanism for the cardiac dysfunction in BMD and DMD offering opportunities to further investigate the organization role of dystrophin in intercellular communication.

Fasting triglyceride concentrations are associated with markers of lipid metabolism and glucose homeostasis in healthy, non-obese dogs in lean and overweight condition.

Serum triglyceride concentrations increase in dogs with obesity, which is typically assessed by body condition score (BCS), however little is known about changes that take place in non-obese dogs in overweight condition. Further, the associations of triglyceride levels with other markers of energy homeostasis are poorly characterised in healthy animals. The present study aimed to evaluate associations between both BCS and triglyceride concentrations with other markers of lipid and glucose metabolism in healthy, non-obese dogs, as well as to assess whether these markers change significantly in non-obese dogs with overweight as compared to their lean counterparts. Serum concentrations of cholesterol, free fatty acids, triglycerides, insulin, glucose and fructosamine were measured in 532 healthy, client-owned dogs, assigned either to 'lean' (BCS: 3-5) or 'overweight' (BCS: 6-7) categories. Generalised linear mixed models were used to assess associations between BCS categories, triglyceride concentrations and other variables, correcting for the effect of breed. Compared with lean dogs, overweight dogs had a greater serum cholesterol concentration (95% CI, 5.3-6.2 mmol/L or 205-237 mg/dL versus 5.1-5.4 mmol/L or 198-210 mg/dL, p = 0.0032), insulin concentration (95% CI, 17.5-22.1 µU/ml versus 16.7-18.0 µU/ml, p = 0.0374) and were older (95% CI, 4.0-5.3 versus 3.4-3.7 years, p = 0.0005). Triglyceride concentrations were positively associated with fructosamine (r 2 = 0.31, p = 0.0012), cholesterol (r 2 = 0.25, p < 0.0001), insulin (r 2 = 0.14, p = 0.0030) and glucose (r 2 = 0.10, p = 0.0014) concentrations, and negatively associated with free fatty acid concentrations (r 2 = 0.11, p < 0.0001). However, there was no association between triglyceride concentrations and age. In conclusion, both BCS and triglyceride concentrations were associated with other markers of glucose and lipid metabolism in non-obese healthy dogs, amongst which those with overweight showed metabolic changes as compared to their lean counterparts. Triglyceride concentrations were associated with an increase in insulin and fructosamine concentrations that might reflect an early-phase impairment in glucose tolerance which, surprisingly, was concurrent with lower basal free fatty acid concentrations.

Epidemiological, clinical, radiographic, echocardiographic findings and outcome in client-owned guinea pigs (Cavia porcellus) with cardiac disease: 80 cases (2010-2021).

OBJECTIVE: To characterize epidemiological, clinical, radiographic, and echocardiographic features of cardiac diseases in guinea pigs examined at a referral exotics center. ANIMALS: 80 guinea pigs. PROCEDURES: Medical records of guinea pigs that had echocardiography performed between June 2010 and January 2021 were reviewed. RESULTS: The percentage of guinea pig patients with cardiovascular disease was 2.8%. Clinical signs included dyspnea (46/80), lethargy (18/80), and anorexia (10/80). The most common physical examination finding was heart murmur (10/80). Radiographic abnormalities included subjective cardiomegaly (37/67), pleural effusion (21/67), and increased lung opacity (40/67). Median (range) vertebral heart score on right lateral (48/67) and ventrodorsal (39/67) projections was 9.0 vertebrae (6.6 to 13.2 vertebrae) and 10.8 vertebrae (7.9 to 13.2 vertebrae), respectively. The most common echocardiographic diagnosis was cardiomyopathy (30/80), categorized as restrictive (11/30), hypertrophic (10/30), or dilated (9/10). Other cardiac diseases included cor pulmonale (21/80), pericardial effusion (18/80), congenital heart disease (6/80), acquired valvular disease (3/80), and cardiovascular mass (2/80). Congestive heart failure was present in 36 of 80. Median survival time from diagnosis was 2.5 months (95% CI, 1.1 to 6.2 months). Animals that died from heart disease had a significantly shorter survival time than those that died from a noncardiac disease (P = .02). CLINICAL RELEVANCE: On radiographs, cardiomegaly, pleural effusion, and alveolar or interstitial lung pattern should be considered as indications for echocardiography in guinea pigs. Cardiomyopathy (restrictive, hypertrophic, or dilated), cor pulmonale, and pericardial effusion were the most common echocardiographic diagnoses. Further studies on diagnosis and treatment of cardiovascular diseases in guinea pigs are needed.

Accuracy of the modified vertebral heart score and the cardio-vertebral ratio for radiographic evaluation of cardiomegaly in ferrets.

Thoracic radiography is commonly used to assess the size of the heart and diagnose cardiac disease in ferrets. Several standardized radiographic heart size indicators have been introduced in this species and values in healthy ferrets have been reported. To date, none of these indicators has been tested in ferrets with cardiac disease. The aim of this prospective and retrospective, analytical observational design study was to assess the accuracy of the modified vertebral heart score (mVHS) and the cardio-vertebral ratio (CVR) in the radiographic detection of cardiomegaly in ferrets. Thoracic radiographs of 24 ferrets with confirmed heart diseases, 22 ferrets with non-cardiac diseases and normal-sized hearts on echocardiogram, and 24 healthy ferrets were mixed and examined by three independent and blinded radiologists who measured mVHS and CVR in right lateral (RL) and ventrodorsal (VD) radiographs. For all readers, ferrets with cardiac disease had significantly higher mVHS and CVR than ferrets without cardiac disease on echocardiography. Optimal cut-points for predicting cardiac enlargement were 6.25 vertebrae and 7.25 vertebrae for RL-mVHS and VD-mVHS, and 1.58 and 1.80 for RL-CVR and VD-CVR, respectively. Using these cut-points, the accuracy was good for indicators measured in RL radiographs (92.9% for RL-mVHS; 91.4% for RL-CVR) and moderate for indicators measured in VD radiographs (88.6% for VD-mVHS; 85.7% for VD-CVR). Findings supported the use of mVHS and CVR for evaluating the size of the heart in diseased ferrets, with caution in values interpretation when pericardial fat prevents precise delineation of the cardiac silhouette contour especially on VD radiographs.

Genome wide association study of 40 clinical measurements in eight dog breeds.

The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1-47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8-78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine.

Clinical, epidemiological and echocardiographic features and prognostic factors in cats with restrictive cardiomyopathy: A retrospective study of 92 cases (2001-2015).

BACKGROUND: Restrictive cardiomyopathy (RCM) is a common primary cardiomyopathy of cats. However, little information is available regarding prognostic variables in large populations of cats with RCM. OBJECTIVES: To characterize the epidemiological, clinical, and echocardiographic features of cats with RCM and to document their survival times and risk factors for cardiac death (CD). ANIMALS: Ninety-two cats with RCM. METHODS: Retrospective study. Diagnosis of RCM was based on echocardiographic and Doppler criteria. Median survival time to CD and adjusted hazard ratios (HR) were estimated by the Kaplan-Meier method and multivariate Cox models, respectively. RESULTS: The feline population (median age [interquartile range], 8.6 years [4.1-12.4]; body weight, 4.0 kg [3.3-4.7]) included 83 cats (90%) with the myocardial RCM form and 9 (10%) with the endomyocardial fibrosis RCM form. Most RCM cats (64/92, 70%) were symptomatic at the time of diagnosis, with dyspnea related to congestive heart failure in 57 of 64 cats (89%). The median survival time of the 69 cats with the myocardial RCM form and available follow-up was 667 days (range, 2-3710 days) considering CD. Independent of age, biatrial enlargement, and arrhythmias, increase of the left atrium (LA)-to-aorta (Ao) ratio (hazard ration [HR], 2.5 per 0.5-unit increase; 95% confidence interval [CI], 1.5-4.2; P < .001) and presence of severe LA enlargement (end-diastolic LA : Ao ≥2; HR, 3.4; 95% CI, 1.3-8.7; P = .01) were significantly associated with shorter time to CD. CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac death is common in RCM cats, and LA enlargement seems independently associated with decreased survival time in these cats.

Interbreed variation of biomarkers of lipid and glucose metabolism in dogs.

BACKGROUND: Markers of lipid and glucose metabolism are used in both clinical practice and research. Detection of abnormal laboratory results often relies on species-specific reference intervals, but interbreed variation can also affect data interpretation. OBJECTIVES: The purpose of the present study was to compare concentrations of selected biochemical variables among different dog breeds. METHODS: We analyzed a database containing information on biochemical variables from 534 dogs belonging to nine different breeds. All dogs were confirmed to be healthy based on history, physical examination, and ancillary tests. Concentrations of glucose, fructosamine, insulin, cholesterol, triglycerides, fatty acids, and C-reactive protein were compared using the nonparametric Kruskal-Wallis and Dunn's tests. RESULTS: All variables tested showed significant interbreed differences, although all breeds remained within the previously established RIs for dogs. Fructosamine, insulin, and cholesterol showed a wide interbreed variation that could affect the interpretation of results. CONCLUSIONS: Breed is an important factor to consider when assessing energy metabolism in dogs, especially for markers like fructosamine, insulin, and cholesterol, which vary considerably among breeds.

Specific features and survival of French bulldogs with congenital pulmonic stenosis: a prospective cohort study of 66 cases.

INTRODUCTION: The objectives of this study were to characterize the epidemiological, clinical, and echocardiographic features of French bulldogs (FBs) with congenital pulmonic stenosis and document their survival times and risk factors for cardiac death (CD). ANIMALS: This study included 66 FBs with congenital pulmonic stenosis. METHODS: Prospective cohort study including a survival analysis to assess time to CD. RESULTS: In most cases (53/66, 80%), at least two obstructive lesions were observed, most commonly valvular and supravalvular (42/66, 64%), with pulmonary trunk hypoplasia in 40/66 (61%) of cases. The median Doppler-derived peak trans-stenotic pressure gradient (ΔP) was very high: 170 mmHg (range = 34-291 mmHg), with ΔP ≥ 200 mmHg in 33% of FBs. Among the 51 FBs with an available follow-up and that did not undergo surgical valvuloplasty, 21/51 (41%) died, 67% (14/21) of deaths being CD. The median survival time from diagnosis to CD was 2.8 years (interquartile range = 0.8-4.6 years). Univariate Cox proportional hazard analyses revealed that age (hazard ratio [HR] = 2.3 per 1 year increase; p = 0.02), clinical signs at presentation (HR = 3.7; p = 0.03), ΔP (HR = 1.2 per 10 mmHg increase; p = 0.01), right ventricular dilation (HR = 5.0; p = 0.04), severe tricuspid regurgitation (HR = 7.6; p = 0.001), and right-sided congestive heart failure (HR = 4.8; p = 0.05) were associated with time to CD. After adjustment for age and ΔP, tricuspid regurgitation remained significantly associated with time to CD (HR = 5.1; p = 0.02). CONCLUSIONS: Pulmonic stenosis in FBs is commonly severe and complex, with at least 2 obstructive lesions in most cases, a high incidence of pulmonary trunk hypoplasia and CD, and strong association between prognosis and tricuspid regurgitation severity.

Quantitative assessment of systolic and diastolic right ventricular function by echocardiography and speckle-tracking imaging: a prospective study in 104 dogs.

Our aim was (1) to determine the within-day and between-day variability of several indices of systolic and diastolic right ventricular (RV) function by using conventional echocardiography and speckle-tracking echocardiography (STE) (Study 1), (2) to quantify these variables in a large healthy canine population (n = 104) with Doppler-derived estimated systolic pulmonary arterial pressure (SPAP) and left ventricular (LV) function, and (3) to establish the corresponding reference intervals (Study 2). For both studies, RV variables included tricuspid annular plane systolic excursion (TAPSE), right fractional area change (RFAC), STE longitudinal systolic strain (StS) of the RV free wall (RVFW) and of the entire RV (i.e., global RV StS), STE longitudinal systolic RVFW strain rate (SRS), and the diastolic early:late strain rate ratio. All but one within- and between-day coefficients of variation (13/14) were ＜ 15%, the lowest being observed for TAPSE (3.6-9.8%), global RV StS (3.8-9.9%), and RVFW StS (3.7-7.3%). SPAP was weakly and negatively correlated with the TAPSE:body weight ratio (rs = -0.26, p = 0.01) and RVFW SRS (rs = -0.23, p ＜ 0.05). Reference intervals (lower and upper limits with 90% confidence intervals) were provided for all variables. STE provides a non-invasive evaluation of RV function that may be used for clinical investigations in canine cardiology.

Epidemiological, clinical, and echocardiographic features and survival times of dogs and cats with tetralogy of Fallot: 31 cases (2003-2014).

OBJECTIVE To characterize the epidemiological, clinical, and echocardiographic features of dogs and cats with tetralogy of Fallot (TOF) and determine their survival times. DESIGN Retrospective case series. ANIMALS 15 dogs and 16 cats with a diagnosis of TOF as determined via echocardiography. PROCEDURES Medical records of dogs and cats were reviewed to extract information on signalment, clinical status at the time of TOF diagnosis, echocardiographic findings, and any outcome data. RESULTS The most common canine breeds were terrier types (n = 7). Most animals (28/31 [90%]) had clinical signs of TOF at the time of diagnosis, including cyanosis (16/31 [52%]). Pulmonic stenosis was characterized by a variable systolic Doppler-derived pressure gradient (median [range], 108 mm Hg [26 to 255 mm Hg]). Most ventricular septal defects were large, with a median (range) ratio of the diameter of the ventricular septal defect to that of the aorta of 0.60 (0.18 to 1.15). Median age at cardiac-related death was 23.4 months, with no significant difference between dogs and cats. Median survival time from TOF diagnosis to cardiac-related death was briefer for animals with no or low-grade heart murmur (3.4 months) than for those with higher-grade heart murmur (16.4 months). After adjustment for age and sex, having a lack of or a low- to mild-grade systolic heart murmur was significantly associated with a briefer survival time. CONCLUSIONS AND CLINICAL RELEVANCE With a few exceptions, cardiac-related death occurred predominantly in young adult dogs and cats with TOF, and most animals had severe clinical signs at the time of TOF diagnosis.

Surgical Treatment of Cor Triatriatum Sinister in a Cat Under Cardiopulmonary Bypass.

OBJECTIVE: To report the surgical repair of cor triatriatum sinister (CTS) incorporating heart-beating cardiopulmonary bypass (CPB) in a cat. STUDY DESIGN: Clinical case report. ANIMAL: Fourteen-month-old, 5.9-kg male castrated Maine Coon cat. MATERIALS AND METHODS: The cat had a 3 month history of inappetance, weight loss, and recurrent pulmonary edema. CTS with severe systolic pulmonary arterial (SPA) hypertension (124 mm Hg) was diagnosed by 2D echocardiography, color flow and continuous wave Doppler modes, and left atrial and pulmonary angiography. Surgery was performed through a left intercostal thoracotomy. CPB was initiated and the heart was kept beating. The left atrial appendage was opened and the intra-atrial membrane was excised. RESULTS: After 48 hours, the cat was doing well. Reduced SPA pressure (52 mm Hg) with decreased right heart enlargement was observed on ultrasound examination and the cat was discharged 6 days after surgery with oral antibiotics for 10 days, aspirin, and furosemide. Four months after surgery, the cat presented with increased activity and weight gain and was completely asymptomatic. Transthoracic echocardiography showed a marked improvement of all echo-Doppler variables with disappearance of SPA hypertension (24 mm Hg). Four years after surgery, the cat was still doing well with no recurrence of clinical signs despite the lack of medical treatment. CONCLUSION: CTS in the cat may be successfully treated by surgery facilitated by use of CPB leading to early and long-term substantial improvement in clinical status and cardiac function. CTS can safely be repaired under CPB in cats.

PREVALENCE OF VALVULAR REGURGITATIONS IN CLINICALLY HEALTHY CAPTIVE LEOPARDS AND CHEETAHS: A PROSPECTIVE STUDY FROM THE WILDLIFE CARDIOLOGY (WLC) GROUP (2008-2013).

The purpose of this prospective study was to evaluate transthoracic echocardiograms from clinically healthy large felids for the presence of valvular regurgitations (VR). Physiologic VR commonly occur in normal dogs and cats, but the percentage of large felids with VR has not been previously reported. During a 5-yr study period (2008-2013), 28 healthy animals were evaluated under general anesthesia: 16 cheetahs (Acinonyx jubatus soemmeringuii) with a mean age of 1.5±0.8 yr (range 0.7-3.5 yr), 5 Amur leopards (Panthera pardus orientalis), 1 snow leopard (Uncia uncia), and 6 clouded leopards (Neofelis nebulosa). For this study, all the leopards were gathered in one so-called "leopards group" with a mean age of 2.8±3.4 yr (range 0.3-10.7 yr). All valves observed in each view were examined for evidence of regurgitant jets and turbulent blood flow using the color-flow Doppler mode. Valves were also examined for structural changes. Mitral valve and aortic cusp abnormalities were considered to be of congenital origin. Mitral valve lesions led to mitral insufficiency in all the felids. Aortic cusp abnormalities led to aortic regurgitation in 94% of the cheetahs and 67% of the leopards. Leopards showed a predominance of early systolic mitral regurgitations, whereas all the mitral regurgitation jets in cheetahs were holosystolic. Tricuspid regurgitation was found in 81% of the cheetahs and in 50% of the leopards, whereas pulmonic regurgitation was detected in 44% of the cheetahs and 33% of the leopards. Interestingly, none of these tricuspid and pulmonic regurgitations were associated with two-dimensional structural valve abnormalities, thus suggesting their physiologic origin, as described in humans, cats, and dogs. In conclusion, subclinical valvular diseases are common in apparently healthy leopards and cheetahs. Longitudinal follow-up of affected animals is therefore required to assess their clinical outcome.

Signalment, clinical features, echocardiographic findings, and outcome of dogs and cats with ventricular septal defects: 109 cases (1992-2013).

OBJECTIVE: To determine the signalment, clinical features, echocardiographic findings, and outcome of dogs and cats with ventricular septal defects (VSDs). DESIGN: Retrospective case series. ANIMALS: 56 dogs and 53 cats with VSDs. PROCEDURES: Medical records of dogs and cats with VSDs diagnosed by means of conventional and Doppler echocardiography were reviewed. Signalment, clinical status, echocardiographic findings, and outcome data were recorded. Variables of interest were analyzed for the study population and subgroups according to species and clinical status. RESULTS: VSDs were isolated (ie, solitary defects) in 53 of 109 (48.6%) patients. Most (82/109 [75.2%]) VSDs were membranous or perimembranous. Terriers and French Bulldogs were commonly represented canine breeds. Most isolated VSDs were subclinical (43/53 [81%]) and had a pulmonary-to-systemic flow ratio < 1. 5 (24/32 [75%]). The VSD diameter and VSD-to-aortic diameter ratio were significantly correlated with pulmonary-to-systemic flow ratio in dogs (r = 0.529 and r = 0.689, respectively) and in cats (r = 0.713 and r = 0.829, respectively). One dog underwent open surgical repair for an isolated VSD and was excluded from survival analysis. Of the remaining animals with isolated VSDs for which data were available (37/52 [71%]), no subclinically affected animals developed signs after initial diagnosis, and median age at death from all causes was 12 years. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs and cats with isolated VSDs had a long survival time; few had clinical signs at diagnosis, and none with follow-up developed clinical signs after diagnosis.

The Shepherds' Tale: A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds.

Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.

Influence of the observer's level of experience on systolic and diastolic arterial blood pressure measurements using Doppler ultrasonography in healthy conscious cats.

The objective of this study was to determine the influence of the observer's level of experience on within- and between-day variability, and the percentage of successful systolic (SAP) and diastolic arterial blood pressure (DAP) measurements obtained by Doppler ultrasonography (DU) in awake cats. For this purpose, six healthy conscious cats were used and four observers with different levels of training performed 144 SAP and DAP measurements on 4 days using DU. Measurements were recorded five consecutive times, and mean values were used for statistical analysis. Only the two most skilled observers - a PhD student in cardiology and a Dipl ECVIM-CA (cardiology) - had within- and between-day coefficients of variation (CVs) for SAP ⩽16% (13-16%). Conversely, the two less experienced observers - a fifth-year student and an assistant - had high between-day CVs (61% and 73%). For DAP, only the most experienced observer (Dipl ECVIM-CA) succeeded in 100% of the attempts, with within- and between-day CVs of 11% and 4%, respectively. Conversely, DAP could not be measured by the other three observers in 8%, 19% and 56% of attempts (from the highest to the lowest level of experience); therefore, the corresponding CV values could not be calculated. In conclusion, SAP may be assessed using DU in healthy awake cats with good repeatability and reproducibility by a well-trained observer. Measurement of DAP is more difficult than of SAP, and needs a longer training period, which represents one of the limitations of DU in cats.

Echocardiography and conventional Doppler examination in clinically healthy adult Cavalier King Charles Spaniels: effect of body weight, age, and gender, and establishment of reference intervals.

OBJECTIVES: The objectives of this study were (1) to assess the potential effect of body weight (BW), age, and gender on the most commonly used echocardiographic and conventional Doppler variables in a large population of healthy Cavalier King Charles Spaniels (CKCS), and (2) to establish the corresponding reference intervals (RI). ANIMALS: 134 healthy adult CKCS. METHODS: Ultrasound examinations were performed by trained observers in awake dogs. M-mode variables included left ventricular (LV) end-diastolic and end-systolic diameters, LV free wall and interventricular septal thicknesses at end-diastole and end-systole, and LV fractional shortening (FS%). The left atrium (LA) and aortic (Ao) diameters were measured using a 2D method, and the LA/Ao was calculated. Pulsed-wave Doppler variables included peak systolic aortic and pulmonary flow velocities, mitral E and A waves, and E/A ratio. Effects of BW, age, and gender on these 15 variables were tested using a general linear model, and RIs were determined by applying the statistical procedures recommended by the Clinical and Laboratory Standards Institute. RESULTS: A significant BW effect was observed for all variables, except LA/Ao, FS%, and mitral E/A ratio. A significant but negligible effect of gender and age was also observed for 5/15 and 4/15 of the tested variables, respectively. Only the BW effect on M-mode variables was considered as clinically relevant and the corresponding regression-based RIs were calculated. CONCLUSIONS: Body weight should be taken into account when interpreting echocardiographic values in CKCS, except for LA/Ao, FS%, and mitral E/A ratio.

Prospective echocardiographic and tissue Doppler screening of a large Sphynx cat population: reference ranges, heart disease prevalence and genetic aspects.

OBJECTIVES: (1) To investigate heart morphology and function using echocardiography and tissue Doppler imaging (TDI), (2) to determine heart disease prevalence and characteristics, and (3) to assess potential genetic features in a population of Sphynx cats presented for cardiovascular screening. ANIMALS: A total of 147 echocardiographic examinations, including 33 follow-ups, were performed by trained observers on 114 Sphynx cats of different ages (2.62 ± 1.93 years [0.5-10.0]) from 2004 to 2011. METHODS: Sphynx cats underwent a physical examination, conventional echocardiography, and, if possible, two-dimensional color TDI. RESULTS: Conventional echocardiographic findings included 75/114 normal (65.8%) and 39/114 (34.2%) abnormal examinations with a diagnosis of either congenital heart diseases (n = 16) or hypertrophic cardiomyopathy (HCM, n = 23). In adult healthy cats, a significant body weight effect was observed for several echocardiographic variables, including end-diastolic left ventricular (LV) free wall (P < 0.01), interventricular septum (P < 0.001), and LV diameter (P < 0.001). Mitral valve dysplasia (MVD) was observed as a single or associated defect in 15/16 cats with congenital heart diseases. A significant increase in HCM prevalence (P < 0.001) was observed according to age. The pedigree analysis of a large family (n = 81) suggested an autosomal dominant mode of inheritance with incomplete penetrance for HCM. CONCLUSIONS: Body weight should be taken into account when interpreting values of diastolic myocardial wall thicknesses in Sphynx cats. Additionally, HCM and MVD are two relatively common heart diseases in this feline breed. More pedigree data are required to confirm the inheritance pattern of HCM at the breed level.

Bradykinin restores left ventricular function, sarcomeric protein phosphorylation, and e/nNOS levels in dogs with Duchenne muscular dystrophy cardiomyopathy.

AIMS: Cardiomyopathy is a lethal result of Duchenne muscular dystrophy (DMD), but its characteristics remain elusive. The golden retriever muscular dystrophy (GRMD) dogs produce DMD pathology and mirror DMD patient's symptoms, including cardiomyopathy. We previously showed that bradykinin slows the development of pacing-induced heart failure. Therefore, the goals of this research were to characterize dystrophin-deficiency cardiomyopathy and to examine cardiac effects of bradykinin in GRMD dogs. METHODS AND RESULTS: At baseline, adult GRMD dogs had reduced fractional shortening (28 ± 2 vs. 38 ± 2% in control dogs, P < 0.001) and left ventricular (LV) subendocardial dysfunction leading to impaired endo-epicardial gradient of radial systolic velocity (1.3 ± 0.1 vs. 3.8 ± 0.2 cm/s in control dogs, P < 0.001) measured by echocardiography. These changes were normalized by bradykinin infusion (1 µg/min, 4 weeks). In isolated permeabilized LV subendocardial cells of GRMD dogs, tension-calcium relationships were shifted downward and force-generating capacity and transmural gradient of myofilament length-dependent activation were impaired compared with control dogs. Concomitantly, phosphorylation of sarcomeric regulatory proteins and levels of endothelial and neuronal nitric oxide synthase (e/nNOS) in LV myocardium were significantly altered in GRMD dogs. All these abnormalities were normalized in bradykinin-treated GRMD dogs. CONCLUSIONS: Cardiomyopathy in GRMD dogs is characterized by profound LV subendocardial dysfunction, abnormal sarcomeric protein phosphorylation, and impaired e/nNOS, which can be normalized by bradykinin treatment. These data provide new insights into the pathophysiological mechanisms accounting for DMD cardiomyopathy and open new therapeutic perspectives.

Relationship between paradoxical breathing and pleural diseases in dyspneic dogs and cats: 389 cases (2001-2009).

OBJECTIVE: To determine the strength of the relationship between paradoxical breathing (PB) and spontaneous pleural diseases in dyspneic dogs and cats. DESIGN: Cross-sectional study. ANIMALS: Dogs (n = 195) and cats (194) with a recorded diagnosis of dyspnea examined at the National Veterinary Schools of Alfort and Toulouse (France) between January 2001 and October 2009. PROCEDURES: Dogs and cats were divided into 2 groups according to the presence or absence of PB. Stratified analysis by species was performed. Signalment of affected animals and occurrence of PB were recorded. The relationship between PB and pleural diseases among dyspneic dogs and cats was analyzed. RESULTS: A strong relationship between PB and pleural diseases was highlighted in multivariate analysis (dogs, OR = 12.6 and 95% confidence interval = 4.6 to 31.2; cats, OR = 14.1 and 95% confidence interval = 6.0 to 33.5). Paradoxical breathing prevalence among dyspneic dogs and cats was 27% and 64%, respectively. Occurrence of pleural diseases in dyspneic animals with and without PB was 49% and 9% in dogs and 66% and 13% in cats, respectively. The sensitivity and specificity of PB as a predictor of pleural diseases were 0.67 and 0.83 in dyspneic dogs and 0.90 and 0.58 in dyspneic cats, respectively. The positive and negative predictive values of PB were 0.49 and 0.91 in dyspneic dogs and 0.66 and 0.87 in dyspneic cats, respectively. Age, sex, feline breeds, and canine morphotypes in patients with PB were not significantly different from those of other dyspneic animals. CONCLUSIONS AND CLINICAL RELEVANCE: PB was strongly associated with pleural diseases in dyspneic dogs and cats. The presence of this clinical sign should prompt small animal practitioners to implement appropriate emergency procedures and guide their diagnostic strategy.

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS.

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 µg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.