Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

OBJECTIVE: To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS. DESIGN: Multicenter, retrospective, case-control study from 2017 to 2021. SETTING: Private referral center and veterinary teaching hospital. ANIMALS: One hundred and thirty-five client-owned dogs that underwent diagnostic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs with stage B1 myxomatous mitral valve disease (MMVD) and dogs diagnosed with precapillary pulmonary hypertension (PCPH) via echocardiograms were reviewed. Dogs were categorized by a cardiologist into 5 groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Cineloops from each case were subjectively evaluated by emergency and critical care residents for the presence of right atrial and ventricular enlargement, right ventricular hypertrophy, interventricular septal flattening, and pulmonary artery and trunk enlargement to form a composite pulmonary hypertension score out of 8 (PHS8). When available, signs of peritoneal effusion and distention of the caudal vena cava were subjectively assessed to generate a pulmonary hypertension score out of 10 (PHS10). There was excellent discrimination of moderate to severe PCPH versus grouped absent to mild PCPH using PHS8 (area under the receiver operator curve [AUC] [95% confidence interval, CI] = 0.90 [0.84-0.95], P < 0.0001) and PHS10 (AUC [95% CI] = 0.89 [0.81-0.97], P < 0.0001). PHS8 ≥3 was 64% sensitive and 98% specific for moderate to severe PCPH (positive likelihood ratio [LR+] 32, negative likelihood ration [LR-] 0.37). PHS10 ≥ 3.3 was 64% sensitive and 92% specific for moderate to severe PCPH (LR+ 8, LR- 0.39). Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC] = 0.74 [95% CI: 0.66-0.80], n = 135). CONCLUSIONS: Residents identified moderate to severe PCPH in dogs using PHS on cineloops previously obtained by a cardiologist. The interrater agreement was good to excellent with limited training. Prospective studies to determine if residents can obtain diagnostic images for PHS are warranted.

Left atrial measurement in lateral versus sternal recumbency in cats undergoing focused cardiac ultrasound examination.

Objective: To compare left atrial measurements carried out by an emergency and critical care (ECC) clinician on cats in lateral and sternal recumbency. Animals and procedures: A prospective observational study was conducted between December 2019 and January 2021 at the university teaching hospital at University of Liège. One hundred and two hospitalized cats were enrolled. Focused cardiac ultrasound (FOCUS) was performed in right lateral and sternal recumbency by a single FOCUS-trained ECC resident. Standard right parasternal long- and short-axis views were recorded. After randomization of the cineloops, the same blinded resident measured maximal left atrial dimension (LAD) and the ratio of left atrial to aortic diameter (LA:Ao). Reproducibility was assessed using the Bland-Altman method. Results: The LA:Ao and LAD measurements in lateral (LA:Ao median: 1.37, range: 1.02 to 3.22; LAD median: 13.25, range: 7.90 to 32.90) and sternal (LA:Ao median: 1.38, range: 1.06 to 3.22; LAD median: 13.00, range: 8.00 to 32.90) recumbency were not significantly different (bias: -0.003, CI -0.014, 0.007; and bias: -0.101, CI -0.231, 0.029, respectively). Conclusions and clinical relevance: The FOCUS technique was successfully applied in sternal recumbency in almost all cats. The LAD and LA:Ao measured in sternal and lateral recumbency were not significantly different. Cardiac left atrial measurements obtained using FOCUS can be reliably assessed in sternal recumbency in hospitalized, stable cats.

Mesure de l'oreillette gauche en décubitus latéral versus sternal chez les chats soumis à une échographie cardiaque focalisée. Objectif: Comparer les mesures de l'oreillette gauche effectuées par un clinicien des urgences et soins intensifs (ECC) sur des chats en décubitus latéral et sternal. Animaux et procédures: Une étude observationnelle prospective a été menée entre décembre 2019 et janvier 2021 au CHU de l'Université de Liège. Cent deux chats hospitalisés ont été enrôlés. L'échographie cardiaque focalisée (FOCUS) a été réalisée en décubitus latéral droit et sternal par un seul résident ECC formé au FOCUS. Des vues parasternales droites grand et petit axe standards ont été enregistrées. Après randomisation des cineloops, le même résident en aveugle a mesuré la dimension auriculaire gauche maximale (LAD) et le rapport entre le diamètre de l'oreillette gauche et celui de l'aorte (LA:Ao). La reproductibilité a été évaluée à l'aide de la méthode de Bland-Altman. Résultats: Les mesures LA:Ao et LAD en décubitus latéral (LA:Ao médian : 1,37, intervalle : 1,02 à 3,22; LAD médian : 13,25, intervalle : 7,90 à 32,90) et sternal (LA:Ao médian : 1,38, intervalle : 1,06 à 3,22; médiane LAD : 13,00, intervalle : 8,00 à 32,90) n'étaient pas significativement différents (biais : −0,003, IC −0,014, 0,007; et biais : −0,101, IC −0,231, 0,029, respectivement). Conclusions et pertinence clinique: La technique FOCUS a été appliquée avec succès en décubitus sternal chez presque tous les chats. Le LAD et LA:Ao mesurés en décubitus sternal et latéral n'étaient pas significativement différents. Les mesures de l'oreillette cardiaque gauche obtenues à l'aide de FOCUS peuvent être évaluées de manière fiable en décubitus sternal chez les chats hospitalisés et stables.(Traduit par Dr Serge Messier).

Osteopontin and fibronectin in lung tissue, serum, and bronchoalveolar lavage fluid of dogs with idiopathic pulmonary fibrosis and control dogs.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) affects West Highland white terriers (WHWTs). Osteopontin (SPP1) and fibronectin (FN1) are associated with human IPF and are overexpressed by bronchoalveolar lavage fluid (BALF) macrophages in dogs with IPF. OBJECTIVE: To investigate the value of these proteins as biomarkers of IPF. ANIMALS: West Highland white terriers (WHWTs) with IPF, control WHWTs, and terriers. METHODS: Cross-sectional observational study. Immunohistochemistry was used to localize SPP1 and FN1 in lung tissue. Serum and BALF SPP1 and FN1 concentrations were measured using canine ELISA kits and compared between groups. RESULTS: Osteopontin stained ciliated epithelial cells, smooth muscular cells, and macrophages of all included dogs, and type-II pneumocytes and extracellular matrix of all 12 diseased WHWTs, 4/6 control WHWTs, and none of the 3 terriers. Osteopontin serum concentration was higher in diseased WHWTs (n = 22; 2.15 ng/mL [0.74-5.30]) compared with control WHWTs (n = 13; 0.63 ng/mL [0.41-1.63]; P = .005) and terriers (n = 15; 0.31 ng/mL [0.19-0.51]; P < .0001), and in control WHWTs compared with terriers (P = .005). Osteopontin BALF concentrations were higher in diseased (0.27 ng/mL [0.14-0.43]) and control WHWTs (0.25 ng/mL [0.14-0.40]), compared with terriers (0.02 ng/mL [0.01-0.08]; P < .0001 and P = .003, respectively). Fibronectin (FN1) serum concentrations were lower in diseased dogs (1.03 ng/mL [0.35-1.48]) and control WHWTs (0.61 ng/mL [0.24-0.65]) compared with terriers (2.72 ng/mL [0.15-5.21]; P < .0001 and P = .0001, respectively). There was no difference in FN1 immunostaining and FN1 BALF concentrations between groups. CONCLUSIONS: Results suggest that SPP1 is involved in pathogenesis of IPF and could predispose that breed to the disease. Osteopontin serum concentration could serve as a diagnostic biomarker of IPF.

Ultrasonographical Assessment of Caudal Vena Cava Size through Different Views in Healthy Calves: A Pilot Study.

Ultrasonographic measurements of the caudal vena cava (CVC) and aorta (Ao) are known as reliable tools to assess intravascular volume status in humans. The aim of this study was to evaluate the feasibility of obtaining ultrasonographical measurements of CVC and Ao in two different views, assess intra- and interobserver variability, and study the effect of sex, age, body weight, and breed on measurements in healthy calves. The diameter and area of CVC and Ao were measured by a single investigator in two anatomic sites (subxiphoid and paralumbar window) in 48 calves aged less than 60 days and then repeated 2.5 months after the first assessment. For intra- and interobserver variability assessment, CVC and Ao measurements were repeated by three observers on five randomly selected calves. CVC and Ao measurements were easily obtained in PV and more difficult to obtain in SV. CVC and Ao area in PV showed high repeatability and reproducibility. A positive correlation was highlighted between age and CVC and Ao measurements in both sites. In conclusion, CVC size assessment by point of care ultrasound can be easily performed at a paralumbar site in calves under 4 months of age and could be used to assess intravascular volume status.

Focused Cardiac Ultrasound to Detect Pre-capillary Pulmonary Hypertension.

Background: Early recognition of pre-capillary (PC) pulmonary hypertension (PH) benefits dogs, allowing earlier treatment and improving prognosis. The value of focused cardiac ultrasound (FCU) to diagnose PH and assess its severity has not been investigated yet. Hypothesis: A subjective 10-point FCU pulmonary hypertension score (PHS) allows diagnosis and assessment of severity of PCPH. Animals: This study involved fifty client-owned dogs. Methods: Dogs, recruited between September 2017 and February 2020, were classified into four categories (no, mild, moderate, and severe PH; C1 to C4, respectively). C1 and C2, and C3 and C4 were regrouped as group 1 and group 2, respectively. A blinded general practitioner assessed four FCU cineloops. Five echocardiographic parameters were subjectively scored, resulting in a total score of 0-10. Non-parametric tests compared global scores between categories and groups. A receiver operating characteristic (ROC) curve determined the cutoff value to differentiate group 1 and group 2. A gray zone approach allowed diagnosing or excluding moderate to severe PH with 90% certitude. Results: Global scores were significantly higher for C4 than for C1, C2, and C3. Global scores of G2 were significantly higher than G1. The ROC curve indicated a cutoff value of 5, discriminating group 1 from group 2 with a sensitivity of 77% and a specificity of 100%. A score of ≥5/10 allowed diagnosing moderate to severe PH with ≥90% certainty while a score of ≤2/10 excluded PH with ≥90% certainty. Conclusions and Clinical Significance: Moderate to severe PCPH can be accurately detected by non-cardiologists using a 10-point FCU PHS score.

Utility of Computed Tomographic Angiography for Pulmonary Hypertension Assessment in a Cohort of West Highland White Terriers With or Without Canine Idiopathic Pulmonary Fibrosis.

West Highland white terriers (WHWTs) affected with canine idiopathic pulmonary fibrosis (CIPF) are at risk of developing precapillary pulmonary hypertension (PH). In humans, thoracic computed tomography angiography (CTA) is commonly used to diagnose and monitor patients with lower airway diseases. In such patients, CTA helps to identify comorbidities, such as PH, that could negatively impact prognosis. Diameter of the pulmonary trunk (PT), pulmonary trunk-to-aorta ratio (PT/Ao), and right ventricle-to-left ventricle ratio (RV/LV) are CTA parameters commonly used to assess the presence of PH. Pulmonary vein-to-right pulmonary artery ratio (PV/PA) is a new echocardiographic parameter that can be used in dogs to diagnose PH. The primary aim of this study was to evaluate the use of various CTA parameters to diagnose PH. An additional aim was to evaluate the correlation of RV/LV measurements between different CTA planes. CTA and echocardiography were prospectively performed on a total of 47 WHWTs; 22 affected with CIPF and 25 presumed healthy control dogs. Dogs were considered to have PH if pulmonary vein-to-right pulmonary artery ratio (PV/PA) measured on 2D-mode echocardiography was less than to 0.7. WHWTs affected with CIPF had higher PT/Ao compared with control patients. In WHWTs affected with CIPF, PT size was larger in dogs with PH (15.4 mm) compared with dogs without PH (13 mm, p = 0.003). A cutoff value of 13.8 mm predicted PH in WHWTs affected with CIPF with a sensitivity of 90% and a specificity of 87% (AUC = 0.93). High correlations were observed between the different CTA planes of RV/LV. Results suggest that diameter of the PT measured by CTA can be used to diagnose PH in WHWTs with CIPF.

The prevalence of pulmonary hypertension assessed using the pulmonary vein-to-right pulmonary artery ratio and its association with survival in West Highland white terriers with canine idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH) is a known co-morbidity in West Highland white terriers (WHWTs) affected with canine idiopathic pulmonary fibrosis (CIPF). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) has recently been described for the detection of pre-capillary PH in dogs. The objective of the present study was to estimate the prevalence of PH at diagnostic, in WHWTs affected with CIPF, by using PV/PA, in comparison with a group of healthy breed-matched controls (CTRLs). Additional study objective was to explore whether the presence of PH at initial diagnosis of CIPF impacted survival time in dogs treated with sildenafil. RESULTS: Twenty-five client-owned WHWTs presented with CIPF and 19 CTRLs were included in the study. PV/PA in either two-dimensional mode (2D) or time-motion mode or both were measured from cineloops in each dog. Dogs were classified according to PV/PA value into non/mild PH (PV/PA measured in 2D ≥ 0.7) or moderate/severe PH (PV/PA < 0.7). Survival data of WHWTs affected with CIPF were extracted from medical record to assess association between presence of PH at diagnosis and outcome. 60 % overall prevalence for moderate/severe PH was estimated in this cohort of WHWTs presented with CIPF vs. 5 % in CTRLS (P = 0.0002). The presence of moderate/severe PH at initial presentation was not associated with survival. CONCLUSIONS: Results of the present study confirm a high prevalence of PH at diagnosis in WHWTs affected with CIPF and highlight the utility of PV/PA as a non-invasive surrogate for assessment of PH in this population.

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.

Assessment of the lung microbiota in dogs: influence of the type of breed, living conditions and canine idiopathic pulmonary fibrosis.

BACKGROUND: Literature about the lung microbiota (LM) in dogs is sparse. Influence of breed and living conditions on the LM in healthy dogs is currently unknown, as well as the influence of chronic respiratory diseases such as canine idiopathic pulmonary fibrosis (CIPF) in West highland white terriers (WHWTs). Aims of this study were (1) to assess the characteristics of the healthy LM according to breed and living conditions, and (2) to study LM changes associated with CIPF in WHWTs. Forty-five healthy dogs divided into 5 groups: domestic terriers (n = 10), domestic shepherds (n = 11), domestic brachycephalic dogs (n = 9), domestic WHWTs (n = 6) (H-WHWTs) and experimental beagles (n = 9) and 11 diseased WHWTs affected with CIPF (D-WHWTs) were included in the study to achieve those objectives. RESULTS: In healthy domestic dogs, except in H-WHWTs, the presence of few discriminant genera in each type of breed was the only LM modification. LM of experimental dogs displayed a change in b-diversity and an increased richness compared with domestic dogs. Moreover, Prevotella_7 and Dubosiella genera were more abundant and 19 genera were discriminant in experimental dogs. LM of both H-WHWTs and D-WHWTs revealed increased abundance of 6 genera (Brochothrix, Curvibacter, Pseudarcicella, Flavobacteriaceae genus, Rhodoluna and Limnohabitans) compared with other healthy domestic dogs. Brochothrix and Pseudarcicella were also discriminant in D-WHWTs compared with H-WHWTs and other healthy domestic dogs. CONCLUSIONS: In domestic conditions, except for H-WHWT, the breed appears to have minor influence on the LM. LM modifications were found in experimental compared with domestic living conditions. LM modifications in H-WHWTs and D-WHWTs compared with other healthy domestic dogs were similar and seemed to be linked to the breed. Whether this breed difference might be related with the high susceptibility of WHWTs for CIPF requires further studies.

Identification of Pro-Fibrotic Macrophage Populations by Single-Cell Transcriptomic Analysis in West Highland White Terriers Affected With Canine Idiopathic Pulmonary Fibrosis.

Canine idiopathic pulmonary fibrosis (CIPF) affects old dogs from the West Highland white terrier (WHWT) breed and mimics idiopathic pulmonary fibrosis (IPF) in human. The disease results from deposition of fibrotic tissue in the lung parenchyma causing respiratory failure. Recent studies in IPF using single-cell RNA sequencing (scRNA-seq) revealed the presence of profibrotic macrophage populations in the lung, which could be targeted for therapeutic purpose. In dogs, scRNA-seq was recently validated for the detection of cell populations in bronchoalveolar lavage fluid (BALF) from healthy dogs. Here we used the scRNA-seq to characterize disease-related heterogeneity within cell populations of macrophages/monocytes (Ma/Mo) in the BALF from five WHWTs affected with CIPF in comparison with three healthy WHWTs. Gene set enrichment analysis was also used to assess pro-fibrotic capacities of Ma/Mo populations. Five clusters of Ma/Mo were identified. Gene set enrichment analyses revealed the presence of pro-fibrotic monocytes in higher proportion in CIPF WHWTs than in healthy WHWTs. In addition, monocyte-derived macrophages enriched in pro-fibrotic genes in CIPF compared with healthy WHWTs were also identified. These results suggest the implication of Ma/Mo clusters in CIPF processes, although, further research is needed to understand their role in disease pathogenesis. Overexpressed molecules associated with pulmonary fibrosis processes were also identified that could be used as biomarkers and/or therapeutic targets in the future.

Interobserver agreement between non-cardiologist veterinarians and a cardiologist after a 6-hour training course for echographic evaluation of basic echocardiographic parameters and caudal vena cava diameter in 15 healthy Beagles.

OBJECTIVE: To evaluate cardiovascular focused assessment with sonography for trauma and triage (CV-FAST) interobserver agreement for echocardiographic parameters and caudal vena cava (CVC) diameter measurement, between a cardiologist and 2 non-cardiologists after a 6-hour training course. SETTING: University veterinary teaching hospital. ANIMALS: Fifteen healthy Beagle dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Echocardiography parameters were assessed via standardized views. Caudal vena cava was assessed via a subxiphoid window (CVC-SubX) using 3 measurements (minimal and maximal CVC diameter, and collapsibility index) and via a dorsolateral window (CVC-DL) using 1 measurement (CVC diameter). Bland-Altman analysis assessed agreement of each non-cardiologist with the cardiologist; coefficients of variation (CoV) quantified variability between observers. The 95% limits of agreement (LOA) and CoVs were considered acceptable for left atrial diameter, left atrium to aortic ratio, normalized left ventricle diameter in diastole and systole but non-acceptable for fractional shortening and pulmonary vein to pulmonary artery ratio. For CVC-SubX, the 95% LOA for maximum CVC diameter were acceptable, while minimum CVC diameter and CVC collapsibility index were non-acceptable. The CoVs were good for maximum and minimum CVC (7%) and poor for collapsibility index (37%). For CVC-DL, the 95% LOA were non-acceptable, although the CoV was considered good (11%). CONCLUSIONS: A 6-hour training course in echocardiography allows non-cardiologists to assess left atrial diameter, left atrium to aortic ratio, normalized left ventricle diameter in diastole and systole, and CVCmax of the CV-FAST exam in healthy Beagles. Standardization of the CVC-SubX technique and assessment of the impact of the respiratory phase on CVC diameter in dogs is needed. Further studies are required to determine whether interobserver agreement remains acceptable when including different breeds. Assessment of basic echocardiographic parameters and the CVC to estimate volume status in small animal medicine merits further clinical evaluation.

Cardiovascular biomarkers in dogs with systemic inflammatory response syndrome.

OBJECTIVE: To measure plasma N-terminal fragments of pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) concentration in hospitalized dogs and relate these markers to underlying conditions and evaluate their potential as prognostic markers in dogs with systemic inflammatory response syndrome (SIRS). DESIGN: Prospective, observational, clinical study. SETTING: Emergency department of a university teaching hospital. ANIMALS: Sixty-nine dogs with SIRS examined in the emergency department were prospectively studied. Patient age ranged from 5 months to 15 years, and weight ranged from 5.5 to 75 kg. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained at presentation, during hospitalization until discharge or death, and at a "control" visit (T1m) at least 1 month after hospital discharge. NT-proBNP was assayed with a commercially available canine ELISA, while cTnT was measured with an automated immunoassay previously used in dogs. A correlation procedure, mixed procedure on a linear model, and a logistic procedure were performed. Forty-four patients survived, 19 of which had control visits. cTnT concentrations were significantly higher than T0 and T1m at T12, T24, and T72. In 28 dogs, cTnT was detected during hospitalization, but cTnT was not detected in any dog at the control visits. Higher concentrations of cTnT were negatively associated with survival, irrespective of disease category. NT-proBNP concentrations were significantly higher than T0, T6, T12, and T1m at T24, T72, and T120, but were not associated with survival. CONCLUSIONS: NT-proBNP and cTnT increased significantly in dogs with SIRS, regardless of the underlying disease process. Nonsurvivors displayed significantly higher cTnT concentrations during hospitalization.

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.

Establishment of reference values of the caudal vena cava by fast-ultrasonography through different views in healthy dogs.

BACKGROUND: Clinical assessment of intravascular volume status is challenging. In humans, ultrasonographic assessment of the inferior vena cava diameter, directly or as a ratio to the aortic diameter is used to estimate intravascular volume status. OBJECTIVES: To ultrasonographically obtain reference values (RV) for caudal vena cava diameter (CVCD ), area (CVCa ) and aortic ratios using 3 views in awake healthy dogs. ANIMALS: One hundred and twenty-six healthy adult dogs from clients, students, faculty, or staff. METHODS: Prospective, multicenter, observational study. Two observer pairs evaluated CVCD by a longitudinal subxiphoid view (SV), a transverse 11th-13th right hepatic intercostal view (HV), and a longitudinal right paralumbar view (PV). Inter-rater agreements were estimated using concordance correlation coefficients (CCC). For body weight (BW)-dependent variables, RVs were calculated using allometric scaling for variables with a CCC ≥ 0.7. RESULTS: The CCC was ≤0.43 for the CVC/aorta ratio at the PV and ≤0.43 in both inspiration and expiration for CVC at the SV. The RVs using allometric scaling for CVCa at the HV for inspiration, expiration, and for CVCD at the PV were 6.16 × BW0.762 , 7.24 × BW0.787 , 2.79 × BW0.390 , respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The CVCD , measured at the HV and PV in healthy awake dogs of various breeds has good inter-rater agreement suggesting these sites are reliable in measuring CVCD . Established RVs for CVCD for these sites need further comparison to results obtained in hypovolemic and hypervolemic dogs to determine their usefulness to evaluate volume status in dogs.

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.

CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.