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Abstract 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.

Abstract 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.

Background: The prognostic use of both the echocardiographic parameters tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) in dogs with pulmonary hypertension (PH) has shown conflicting results. The ratio of TAPSE/sPAP, not yet described in dogs, is used for the evaluation and risk assessment in people with PH and is a validated surrogate for right ventricular to pulmonary artery coupling with lower values being associated with poor outcome. This study aimed to describe TAPSE/sPAP in dogs with precapillary PH (PCPH) due to various diseases. It demonstrates the correlation of this ratio with echocardiographic indices, its association with heart failure (HF) and its prognostic value. Methods: Medical records and echocardiographic data from 95 client-owned dogs with estimated mild (n = 10), moderate (n = 31) or severe (n = 54) PCPH were retrospectively reviewed. Body weight-independent TAPSE/sPAP ratios were obtained, and short-term and overall survival until death from all causes or cardio-pulmonary death (CPD) were assessed. Results: TAPSE/sPAP was lower in dogs with HF and correlated with other echocardiographic variables commonly altered in dogs with PCPH. Different TAPSE/sPAP ratios, such as nTAPSE/(sPAP(m/s)), were independent predictors of short-term CPD, as was having pulmonary thromboembolism. For overall survival only HF was a risk factor of CPD. The cut-off value of <1.05 for nTAPSE/(sPAP(m/s)) was associated with shorter survival for dogs dying from CPD. Conclusions: The TAPSE/sPAP ratio is a non-invasive echocardiographic parameter that provides prognostic information, especially in short-term survival, in dogs with PCPH and may aid in risk stratification.

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.

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.

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.

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.

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. A subjective 10-point FCU pulmonary hypertension score (PHS) allows diagnosis and assessment of severity of PCPH. This study involved fifty client-owned dogs. 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. 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. Moderate to severe PCPH can be accurately detected by non-cardiologists using a 10-point FCU PHS score.

To determine interobserver variability of left ventricular eccentricity indices measurements in systole (EIs), diastole (EId) and at maximum flattening (EIm) by emergency and critical care residents on prerecorded cineloops in dogs with or without pulmonary hypertension. To assess whether these EI measurements allow to identify dogs with right heart changes compatible with moderate to severe pulmonary hypertension (PAH). Multicenter, retrospective, case-control study from 2017 to 2021. 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 five groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Four blinded emergency and critical care residents measured EIs, EId and EIm. One hundred and forty-five client-owned dogs were included. Interobserver agreement was strong, with an intraclass correlation coefficient (ICC) of 0.737 (95% CI: 0.621-0.852) across all eccentricity indices for the full study population and 0.768 (0.642-0.856) for the PAH group specifically. EIs, EId, and EIm were significantly higher in the PAH group compared to control and MMVD groups ( < 0.0001). The differentiation between moderate-to-severe and mild/absent PAH by EIs, EId, and EIm resulted in AUCs of 0.738, 0.834, and 0.766, with cut-off values of 1.40, 1.34, and 1.28, respectively. A gray zone approach identified 90% sensitivity for EIs (1.12), EId (1.15), and EIm (1.23), and specificity for EIs (2.27), EId (1.32), and EIm (2.1) to rule out or diagnose moderate-to-severe PAH. This study showed good inter-observer agreement of EIs, EIm, and EId measurement by ECC residents on prerecorded loops. EI allowed good identification of dogs with moderate to severe PAH by ECC residents.

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.