Phosphoproteomics analysis of serum from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease.

Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Phosphorylation of proteins, impacting vascular function and cell proliferation, might play a role in the development and progression of PH. Unlike gene or protein studies, phosphoproteomic focuses on active proteins that function as end-target proteins within signaling cascades. Studying phosphorylated proteins can reveal active contributors to PH development. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach. Serum samples were collected from healthy control dogs (n = 28), dogs with DMVD (n = 24), and dogs with DMVD and PH (n = 29). Phosphoproteins were enriched from the serum samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data analysis was performed to identify uniquely expressed phosphoproteins in each group and differentially expressed phosphoproteins among groups. Phosphoproteomic analysis revealed nine uniquely expressed phosphoproteins in the serum of dogs in the DMVD+PH group and 15 differentially upregulated phosphoproteins in the DMVD+PH group compared to the DMVD group. The phosphoproteins previously implicated in PH and associated with pulmonary arterial remodeling, including small nuclear ribonucleoprotein G (SNRPG), alpha-2-macroglobulin (A2M), zinc finger and BTB domain containing 42 (ZBTB42), hemopexin (HPX), serotransferrin (TRF) and complement C3 (C3), were focused on. Their unique expression and differential upregulation in the serum of DMVD dogs with PH suggest their potential as biomarkers for PH diagnosis. In conclusion, this phosphoproteomic study identified uniquely expressed and differentially upregulated phosphoproteins in the serum of DMVD dogs with PH. Further studies are warranted to validate the diagnostic utility of these phosphoproteins.

Proteomic analysis of the serum in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease: the preliminary study.

Background: Pulmonary hypertension (PH) is a common complication in dogs with myxomatous mitral valve disease (MMVD), characterized by elevated blood pressure in pulmonary artery. Echocardiography is a reliable technique for PH diagnosis in veterinary medicine. However, it is limited to use as an early detection method. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has found extensive application in the discovery of serum protein biomarkers for various diseases. The objective of this study was to identify serum proteins in healthy control dogs and MMVD dogs both with and without PH using LC-MS/MS. Materials and methods: In this research, a total of 81 small-breed dogs participated, and they were categorized into three groups: the control (n = 28), MMVD (n = 24) and MMVD+PH (n = 29) groups. Serum samples were collected and analyzed by LC-MS/MS. Results: Differentially expressed proteins were identified, and the upregulated and downregulated proteins in MMVD+PH group including Myomesin 1 (MYOM1) and Histone deacetylase 7 (HDAC7), Pleckstrin homology domain containing M3 (PLEKHM3), Diacylglycerol lipase alpha (DAGLA) and Tubulin tyrosine ligase like 6 (TTLL6) were selected as proteins of interest in MMVD dogs with PH. Conclusion: Different types of proteins have been identified in healthy dogs and MMVD dogs with and without PH. Additional studies are needed to investigate the potential of these proteins as biomarkers for PH in dogs with MMVD.

Proteomic analysis of pulmonary arteries and lung tissues from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease.

In dogs with degenerative mitral valve disease (DMVD), pulmonary hypertension (PH) is a common complication characterized by abnormally elevated pulmonary arterial pressure (PAP). Pulmonary arterial remodeling is the histopathological changes of pulmonary artery that has been recognized in PH. The underlying mechanisms that cause this arterial remodeling are poorly understood. This study aimed to perform shotgun proteomics to investigate changes in protein expression in pulmonary arteries and lung tissues of DMVD dogs with PH compared to normal control dogs and DMVD dogs without PH. Tissue samples were collected from the carcasses of 22 small-sized breed dogs and divided into three groups: control (n = 7), DMVD (n = 7) and DMVD+PH groups (n = 8). Differentially expressed proteins were identified, and top three upregulated and downregulated proteins in the pulmonary arteries of DMVD dogs with PH including SIK family kinase 3 (SIK3), Collagen type I alpha 1 chain (COL1A1), Transforming growth factor alpha (TGF-α), Apoptosis associated tyrosine kinase (AATYK), Hepatocyte growth factor activator (HGFA) and Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) were chosen. Results showed that some of the identified proteins may play a role in the pathogenesis of pulmonary arterial remodeling. This study concluded shotgun proteomics has potential as a tool for exploring candidate proteins associated with the pathogenesis of PH secondary to DMVD in dogs.

Investigation of red blood cell and platelet indices in adult dogs suffered from myxomatous mitral valve disease with and without pulmonary hypertension.

Background: Pulmonary hypertension (PH) is a common complication of cardiopulmonary disease. In dogs, PH commonly occurs secondary to myxomatous mitral valve disease (MMVD). Red blood cell and platelet indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), mean platelet volume (MPV) and platelet distribution width (PDW), have previously been found to be indicators for predicting and prognosing PH in humans. Therefore, this study aimed to investigate whether these indices are associated with MMVD and/or PH in dogs. Methods: Two hundred and forty-six dogs were retrospectively recruited for the study and classified into 4 groups: normal (n = 49), MMVD (n =102), PH (n =17), MMVD+PH (n =78). A sub-analysis was performed in dogs with MMVD without evidence of PH according to stage B1 (n =20), stage B2 (n =15), stage C (n =67). The data are expressed as median (interquartile range). Results and discussion: No significant differences (p < 0.05) were found in MCV, RDW and MPV among all groups (normal, MMVD, PH and MMVD+PH). However, decreases in MCH and MCHC were found in MMVD [22.40 (20.90-23.50) pg and 35.25 (33.08-36.90) g/dL], MMVD+PH [22.25 (20.85-23.98) pg and 35.65 (33.30-37.33) g/dL] and PH groups [21.20 (20.60-22.20) pg and 33.80 (32.75-35.70) g/dL] compared to the normal dogs [24.29 (23.55-24.90) pg and 38.20 (37.50-39.05) g/dL] (p < 0.001). Decreases in PDW were found in dogs in the MMVD+PH [15.10 (14.98-15.30) %] groups compared to dogs in the normal group [15.30 (15.10-15.50) %] (p = 0.004). Sub-analysis of MMVD dogs without PH showed a decrease in MCH in dogs with stage B2 MMVD [21.00 (20.50-22.90) pg] and stage C MMVD [22.40 (20.90-23.20) pg] compared to normal dogs [24.29 (23.55-24.90) pg] (p < 0.001). MCHC of dogs with stage B1 [36.55 (33.53-37.78) g/dL] (p = 0.004), B2 [32.90 (32.00-35.00) g/dL] (p < 0.001) and C MMVD [35.30 (33.30-36.80) g/dL] (p < 0.001) were lower than those of normal dogs [38.20 (37.50-39.05) g/dL]. PDW in the stage C MMVD group [15.10 (15.00-15.30) %] was reduced compared to the normal group [15.30 (15.10-15.50) %] (p = 0.042) and the stage B1 MMVD group [15.35 (15.23-15.68) %] (p = 0.002). MCH, MCHC and PDW were negatively correlated with the left atrial and left ventricular size. Conclusion: Decreases in MCH and MCHC are related to MMVD, precapillary PH and postcapillary PH while PDW are associated with MMVD severity but not with the presence of PH.

Rapid identification of canine uropathogens by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry and the clinical factors that correlated bacterial species and antimicrobial resistance.

Using the matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) method for bacterial diagnosis, rapid urine sample preparation can reduce time relapsing of diagnosis and improve discriminatory power in coinfection cases. We aimed to evaluate rapid urine preparation procedures before MALDI-TOF MS application using dog clinical urine samples in comparison with standard microbiological diagnostic methods by agreement analysis. We determined the frequency and distribution of bacteria and bacterial resistance and their correlations to clinical history. Three experimental procedures comprising direct centrifugation, 10% sodium dodecyl sulfate digestion, and ultrasonic preparation were performed for method validation and sensitivity. Sterile urine containing Escherichia coli and/or Staphylococcus aureus were used as simulated samples. By ultrasonic preparation, the microorganisms could be detected 1.46-1.51 × 105 CFU, which was considered the most suitable technique. This preparation was significantly consistent with the routine method based on data from Hospital Information Systems for 50 urine samples from canine cystitis. By standard protocol, Enterobacteriaceae and Staphylococcus pseudintermedius were found in most of the 155 urine samples with cystitis. Extended-spectrum beta-lactamase-producing Enterobacteriaceae was found in 25-30% of the samples. Imipenem resistance was found in 70% of Acinetobacter baumannii cases; almost all were resistant to second-generation fluoroquinolones and tetracyclines. The most efficient antibiotic for treating bacterial urinary tract infection was amoxicillin plus clavulanic acid. A. baumannii and Pseudomonas aeruginosa were susceptible to pradofloxacin. Prolonged urine catheterization was linked to lower urinary tract infections by Enterobacter spp., which also correlated with chronic kidney disease.

Assessment of left atrial myocardial deformation using two-dimensional speckle-tracking echocardiography in cats with cardiogenic and non-cardiogenic arterial thromboembolism.

Arterial thromboembolism (ATE) in cats usually relates to cardiogenic causes that can be diagnosed by conventional echocardiography. Two-dimensional speckle-tracking echocardiography (2D-STE) is a new ultrasound modality with higher sensitivity. Our objective was to investigate left atrial myocardial deformation in cats with both cardiogenic and non-cardiogenic ATE and normal cats using 2D-STE. Twenty-three normal cats and 21 cats with ATE cats were recruited and performed conventional echocardiography and 2D-STE. From the results, left atrial (LA) strain and strain rate from 2D-STE were significantly decreased in cats with cardiogenic ATE (P < 0.001), but there was no significant difference in non-cardiogenic ATE compared with normal cats. From the correlation test, the use of left atrial strain during the reservoir phase (LASr) could represent the overall LA deformation. The intra- and inter-observer coefficient of variation of LASr was less than 15%. The logistic regression revealed that the LASr value of less than 11% was a significant factor for the occurrence of ATE (odd ratio = 189.0, P < 0.001). In conclusion, LASr derived by 2D-STE is a repeatable and non-invasive technique to assess LA myocardial deformation in cats with ATE. By 2D-STE, impaired LA function was detected in cats with cardiogenic ATE. LASr < 11% may use as a predictor of the risk of ATE occurrence in cats.

Perivascular inflammatory cells and their association with pulmonary arterial remodelling in dogs with pulmonary hypertension due to myxomatous mitral valve disease.

Pulmonary hypertension (PH), an increase in pulmonary arterial pressure (PAP), may occur in dogs affected with myxomatous mitral valve disease (MMVD). Recent studies suggest that an accumulation of perivascular inflammatory cells may be involved with medial thickening which is a sign of the pulmonary artery remodelling in PH. The aim of this study was to characterise perivascular inflammatory cells in the surrounding pulmonary arteries of dogs with PH due to MMVD compared to MMVD dogs and healthy control dogs. Nineteen lung samples were collected from cadavers of small-breed dogs (control n = 5; MMVD n = 7; MMVD + PH n = 7). Toluidine blue stain and multiple IHC targeting α-SMA, vWF, CD20, CD68 and CD3 was performed to examine intimal and medial thickening, assess muscularisation of the small pulmonary arteries and characterise perivascular leucocytes. Medial thickening without intimal thickening of pulmonary arteries and muscularisation of normally non-muscularised small pulmonary arteries was observed in the MMVD and MMVD + PH groups compared with the control group. The perivascular numbers of B lymphocytes, T lymphocytes and macrophages was significantly increased in the MMVD + PH group compared with the MMVD and control groups. In contrast, the perivascular number of mast cells was significantly higher in the MMVD group compared with the MMVD + PH and control groups. This study suggested that pulmonary artery remodelling as medial thickening and muscularisation of the normally non-muscular small pulmonary arteries is accompanied by the accumulation of perivascular inflammatory cells.

Indicators for pulmonary hypertension in dogs with degenerative mitral valve disease.

Background and Aim: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD) in dogs. This study aimed to determine PH indicators in dogs with stage C DMVD through thoracic radiography and M-mode and 2-dimensional echocardiography. Materials and Methods: A retrospective study of 133 dogs with DMVD stage C was conducted. The patients were divided into two groups: DMVD and DMVD with PH. Characteristics, thoracic radiographic findings, and echocardiographic variables were recorded for analysis. Results: Pulmonary hypertension was diagnosed in 56 dogs, with a prevalence of 42.1%. Univariable logistic regression analysis revealed associations among PH and right-sided heart enlargement, pulmonary artery enlargement, left ventricular size, and percent fractional shortening. Multivariable logistic regression analysis demonstrated that pulmonary artery enlargement (odds ratio [OR]: 5.96; 95% confidence interval [CI]: 1.45-24.54; p = 0.014) and decreased left ventricular size (OR: 0.02; 95%CI: 0.003-0.13; p = 0.001) were significantly associated with PH. The accuracy of predicting PH in dogs at DMVD stage C using pulmonary artery enlargement combined with decreased left ventricular size was moderate (area under the curve [AUC] 0.77; 95%CI: 0.68-0.86). Conclusion: Pulmonary hypertension is common in dogs with DMVD stage C. The presence of pulmonary artery enlargement assessed by radiography and decreased left ventricular size assessed by echocardiography, were associated with PH and may serve as predictors of PH in DMVD stage C.

Investigation of Genes and Proteins Expression Associating Serotonin Signaling Pathway in Lung and Pulmonary Artery Tissues of Dogs with Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease: The Preliminary Study.

Pulmonary hypertension (PH) is defined as an increase in pulmonary vascular pressure. It is one of the most common complications that occur as a result of degenerative mitral valve disease (DMVD) in dogs. Serotonin (5-HT) can trigger the development of PH. Accordingly, this study investigated the changes in the expression of genes and proteins associated with local 5-HT signaling in the lungs and pulmonary arteries (PA) of dogs with PH secondary to DMVD. Lung and PA tissue samples were collected from the cadavers of fourteen small-breed dogs and divided into normal (n = 4), DMVD (n = 5) and DMVD with PH (n = 5) groups. Gene expression (tph1, slc6a4 and htr2a) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of proteins (TPH-1, SERT, 5-HTR2A, ERK1/2 and pERK1/2) was examined by Western blot analysis and immunohistochemical staining. The results showed that the expression of genes and proteins evaluated by qRT-PCR and Western blot analysis in lung and PA tissues did not differ among groups. However, the expression of proteins related to 5-HT signaling tended to be upregulated in PA tissues from DMVD dogs with and without PH. Immunohistochemical examination revealed the overexpression of these proteins in the DMVD and DMVD with PH groups in lung tissue. These findings suggest a local effect of 5-HT signaling in DMVD dogs with and without PH.

Factors related to survival time in dogs with pulmonary hypertension secondary to degenerative mitral valve disease stage C.

Pulmonary hypertension (PH) is a common complication in dogs with degenerative mitral valve disease (DMVD). The aim of this study was to determine the survival time and to determine factors related to the survival time of dogs with PH secondary to DMVD stage C. A retrospective study was conducted in 37 dogs with PH secondary to DMVD stage C to analyse the median survival time and associated factors such as age, sex, breed, body weight, the presence of syncope, heart rate, systolic blood pressure, manifestation of congestive heart failure (CHF), vertebral heart score (VHS), the presence of left or right heart enlargement, probability of PH and medication. Data were analysed using the Log-Rank test and plotted with the Kaplan-Meier curve. The results showed that the median survival time of dogs with PH secondary to DMVD stage C was 368 days, and factors that shortened the median survival time of dogs with PH secondary to DMVD stage C were mixed breeds, VHS > 11.5, the presence of right heart enlargement, ascites and high probability of PH. Factors associated with an increased hazard of death were mixed breed dogs, dogs with right heart enlargement and ascites. These findings may be useful for the prognosis and management of dogs with PH secondary to DMVD stage C.

Expression of apoptotic proteins in the pulmonary artery of dogs with pulmonary hypertension secondary to degenerative mitral valve disease.

Degenerative mitral valve disease (DMVD) is a common cause of pulmonary hypertension (PH) in dogs. Medial thickening of the pulmonary artery is a common histopathological change in PH. The cause of medial thickening could be a decrease in apoptosis of pulmonary arterial smooth muscle cells (SMCs). This study aimed to detect the expression of apoptosis-related proteins in the pulmonary artery of dogs with PH secondary to DMVD (DMVD+PH) compared with DMVD without PH (DMVD) and healthy dogs (control). Lung samples were collected from three groups, including the control (n = 5), DMVD (n = 7) and DMVD+PH (n = 7) groups. Masson trichrome, α-SMA and apoptotic proteins including Bax, Bcl2 and caspase-3 and -8 were stained. The results showed that the percentage of medial thickness (%MT) and the average number of pulmonary arterial SMCs were greater in the DMVD and DMVD+PH groups than in the control group, and they were greatest in the DMVD+PH group. Bax, Bcl2, and caspase-3 and -8 were mainly expressed in the medial layer of the pulmonary artery. The percentage of Bax and caspase-3 and -8 positive cells was higher in the DMVD group than in the DMVD+PH group, whereas the percentage of Bcl2 positive cells was increased in the DMVD+PH group. These results suggested that the pro-apoptotic activity of pulmonary arterial SMCs occurred mainly in the DMVD group and decreased dramatically in the DMVD+PH group. In conclusion, an increase in medial thickness in dogs with PH secondary to DMVD may relate to a decrease in pro-apoptotic activity of pulmonary arterial SMCs.

First cases of SARS-CoV-2 infection in dogs and cats in Thailand.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic in humans since late 2019. Here, we investigated SARS-CoV-2 infection in dogs and cats during COVID-19 quarantine at private veterinary hospitals in Thailand. From April to May 2021, we detected SARS-CoV-2 in three out of 35 dogs and one out of nine cats from four out of 17 households with confirmed COVID-19 patients. SARS-CoV-2 RNA was detected from one of the nasal, oral, rectal and environmental swabs of dog-A (15 years old, mixed breed, male dog), cat-B (1 year old, domestic shorthair, male cat), dog-C (2 years old, mixed breed, female dog) and dog-D (4 years old, Pomeranian, female dog). The animals tested positive for SARS-CoV-2 RNA from 4 to 30 days after pet owners were confirmed to be COVID-19 positive. The animals consecutively tested positive for SARS-CoV-2 RNA for 4 to 10 days. One dog (dog-A) showed mild clinical signs, while the other dogs and a cat remained asymptomatic during quarantine at the hospitals. SARS-CoV-2 specific neutralizing antibodies were detected in both the dogs and cat by surrogate virus neutralization tests. Phylogenetic and genomic mutation analyses of whole genome sequences of three SARS-CoV-2 strains from the dogs and cat revealed SARS-CoV-2 of the Alpha variant (B.1.1.7 lineage). Our findings are suggestive of human-to-animal transmission of SARS-CoV-2 in COVID-19-positive households and contamination of viral RNA in the environment. Public awareness of SARS-CoV-2 infection in pet dogs and cats in close contact with COVID-19 patients should be raised.

Usefulness of peripheral venous blood gas analyses in cats with arterial thromboembolism.

Feline arterial thromboembolism (ATE) is a condition with a high mortality rate. Acid-base abnormalities may be beneficial to the prognosis of cats with ATE. Venous blood gas and electrolytes data on the first day of ATE presentation of 47 cats with ATE were retrospectively reviewed and analysed. The Cox and logistic regression were analysed to evaluate the relationship between acid-base parameters and death. The most common venous acid-base disorder was simple metabolic acidosis. Age, body weight, and partial venous pressure of carbon dioxide (PvCO2) differed between the dead and alive groups within 7 days of the onset of ATE presentation (p < 0.05). Cox-regression showed that increasing age (HR=1.175 [95% CI: 1.027-1.343], p = 0.019), increasing PvCO2 (HR=1.066 [95% CI: 1.010-1.125], p = 0.021) and PvCO2 more than 34 mmHg (HR=7.878 [95% CI: 1.036- 59.915], p = 0.046) were associated with increased hazard of death. Multivariable logistic regression showed that age > 5 years (OR=9.030, 95% CI: 1.258- 64.823; p=0.029), and PvCO2 > 34 mmHg (OR=21.764, 95% CI: 1.747-271.141; p=0.017) were associated with an increased risk of death, while concomitant administration of enoxaparin with clopidogrel (OR=0.111, 95% CI: 0.015-0.795; p=0.029) were associated with a decreased risk of death within 7 days of the onset of ATE presentation. This study demonstrated the power of venous blood gas analysis which may be used as prognostic indicators for cats with ATE.

Evaluation of pleural fluid parameters related to cardiac diseases in cats.

BACKGROUND AND AIM: Cardiac disease is common in cats, and concurrent pleural effusion can worsen the prognosis. However, the definitive diagnosis of feline cardiac disease by echocardiography is limited in some areas. This study was designed to determine the indicators from fluid analysis obtained from pleural effusion to help diagnose cardiac disease in cats. MATERIALS AND METHODS: A retrospective study was conducted. Data of 61 cats with pleural effusion were retrieved. The cats were divided into two groups: Cardiac disease (n=34) and non-cardiac disease (n=27) groups. Sex, neuter status, breed, age, weight, physical findings, fluid analysis results, radiographic findings, echocardiographic findings, and the presence of other diseases or conditions were recorded. RESULTS: The Chi-square test showed the relationship between cardiac disease and the presence of abnormal heart sounds (p=0.0003), the N-terminal pro-B-type natriuretic peptide-positive result from serum samples (p=0.046), the presence of arterial thromboembolism (p<0.00001), and the presence of radiographic evidence of cardiomegaly and pulmonary edema (p=0.0002 and 0.001, respectively). The Mann-Whitney U-test showed a significant difference in protein concentration and specific gravity between the cardiac and non-cardiac disease groups (p=0.012 and 0.009, respectively). The decision tree classification method showed that protein concentrations of ≤3 g/dL were related to cardiac disease (sensitivity, 41.2% and specificity, 92.6%). CONCLUSION: The protein concentration in the pleural fluid may be used to distinguish cardiac and non-cardiac diseases in cats.

Assessment of Platelet and Plasma Serotonin in Canine Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease.

Background: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD), the most common cardiovascular disease in dogs. Serotonin has been suspected to play a role in the pathogenesis of PH, so this study aimed to investigate the differences in platelet and plasma serotonin between normal, DMVD and DMVD with PH (DMVD+PH) dogs. Materials and Methods: Sixty-two small-breed dogs were enrolled to the study and divided into the normal (n = 22), DMVD (n = 20), and DMVD+PH (n = 20) groups. The platelet and plasma serotonin concentrations were measured by the competitive ELISA. Results: The Kruskal-Wallis revealed the difference among the four groups of normal (179.73 [102.37-352.24] ng/109 platelets), DMVD (325.99 [96.84-407.66] ng/109 platelets), DMVD with intermediate probability of PH (291.11 [106.69-400.84] ng/109 platelets) and DMVD with high probability of PH (35.82 [2.69-126.35] ng/109 platelets) (p = 0.014). The Dunn's post-hoc test showed a decrease in the platelet serotonin concentration of the DMVD dogs with high probability of PH compared to the DMVD group (p = 0.008). The plasma serotonin concentration was not different between normal, DMVD, and DMVD+PH dogs. Conclusion: In conclusion, a decrease in platelet serotonin concentration, which is associated with a degree of PH probability was found in DMVD dogs with PH. Further studies investigating roles of platelet serotonin in PH secondary to DMVD should be performed.

Corrigendum: The Expression of Proteins Related to Serotonin Pathway in Pulmonary Arteries of Dogs Affected With Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease.

[This corrects the article DOI: 10.3389/fvets.2020.612130.].

Left ventricular systolic function in dogs with pulmonic stenosis.

BACKGROUND AND AIM: Pulmonic stenosis (PS) is the most common congenital heart disease in dogs. This condition causes right ventricle (RV) overload and disrupts overall systolic function. The aim of this study was to examine the alterations of cardiac electrical activity and mechanical function in dogs with PS compared to normal healthy dogs. MATERIALS AND METHODS: The ventricular systolic function of dogs with PS was studied. Dogs were divided into two groups, PS (n=13) and control (CONT) (n=12). Measurements of blood pressure, electrocardiography (ECG), and echocardiography were performed. RESULTS: PS dogs had exercise intolerance, with six experiencing syncope. ECG of PS dogs showed higher amplitudes of P, S, and T waves (p<0.01), and a lower R:S ratio (p<0.001) with longer QRS duration (p<0.001) compared to CONT dogs. Echocardiography demonstrated that the pulmonic flow velocity and pressure gradient (PG) between the RV and the pulmonary artery of PS dogs were significantly higher than CONT dogs (p<0.001). The RV free wall thickness to the left ventricular posterior wall thickness ratio and the right atrium to the left atrium diameter ratio was higher (p<0.001), while interventricular septum (IVS) was thicker (p<0.01) in PS dogs compared with CONT dogs (p<0.001). The systolic function in PS dogs showed higher pulmonic valve velocity time integral (PVVTI) value (p<0.001) and longer pulmonic valve ejection time (ET) (p<0.05) than CONT dogs. However, aortic valve VTI (AVVTI) value and aortic valve ET were not significantly different between the groups, although fractional shortening in PS dogs was higher. In PS dogs, PG showed a significant positive correlation with PVVTI: AVVTI ratio (p<0.05). CONCLUSION: PS had prolonged pulmonic valve opening. The thickening of the RV wall and IVS can cause a detrimental reduction of the left ventricular preload in PS dogs.

Short-term effects of sildenafil in the treatment of dogs with pulmonary hypertension secondary to degenerative mitral valve disease.

BACKGROUND AND AIM: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD). Sildenafil, a phosphodiesterase-5 inhibitor, has effects in reducing pulmonary arterial pressure by selectively dilating pulmonary vessels. The study aimed to evaluate the effects of sildenafil in combination with conventional therapy in dogs with PH caused by DMVD. MATERIALS AND METHODS: Fourteen dogs diagnosed with PH secondary to DMVD Stage C on conventional therapy were randomly assigned to placebo (n=7) and sildenafil (n=7) groups. On day 0, the recruited dogs underwent physical examinations, clinical score assessments, electrocardiography, systolic blood pressure measurements, blood collection, thoracic radiography, and echocardiography for baseline. The dogs then received a combination of conventional therapy with sildenafil or placebo every 8 h for 1 week. On day 7, all dogs underwent the baseline evaluations again. RESULTS: The sildenafil group experienced a significant decrease in estimated systolic pulmonary artery pressure (sPAP) (p=0.043) from day 0 to day 7. Moreover, the total clinical scores were decreased in dogs treated with sildenafil relative to those who received the placebo (p=0.007); however, the lung scores were not different between before and after treatment with sildenafil. CONCLUSION: Sildenafil had a synergistic effect with conventional therapy in reducing the estimated sPAP and clinical scores in dogs with PH secondary to DMVD.

Assessment of left atrial function in feline hypertrophic cardiomyopathy by using two- dimensional speckle tracking echocardiography.

BACKGROUND: Left atrial (LA) function plays an important role in diastolic dysfunction in cats with hypertrophic cardiomyopathy (HCM). Two-dimensional speckle tracking echocardiography (2D-STE) is a technique for assessing LA function. This study aimed to evaluate the LA function in HCM cats compared to normal cats, using 2D-STE. RESULTS: Seventeen client-owned cats affected with HCM and twenty healthy control cats were studied. Conventional echocardiographic and 2D-STE variables were measured and compared between groups (control and HCM groups). Variability of the peak atrial longitudinal strain (PALS) displayed good reproducibility with 4.7% intra-observer and 14% inter-observer repeatability. The mean value of PALS in the HCM group (13.16 ± 8.64) was lower than that in the control group (28.54 ± 10.31) (P < 0.001). PALS was lowest in the LA roof region. The atrial longitudinal strains of septal and lateral regions were significantly lower in the HCM group than in the normal group. The PALS correlated with the percentage of the LA fractional shortening (LA-FS) (r = 0.538, P = 0.001), the percentage of the LA ejection fraction (LA-EF) (r = 0.797, P < 0.001), and the LA fractional area change (FAC) (r = 0.746, P < 0.001). CONCLUSIONS: PALS is a feasible and reproducible method to evaluate the LA function in cats affected with HCM.

Accuracy of methods for diagnosing heart diseases in cats.

AIM: This study aimed to determine the accuracy of the current methods for diagnosing heart diseases in cats. MATERIALS AND METHODS: The data of 58 cats were retrospectively retrieved. Cats were classified into two groups: Thirty-eight cats with heart diseases and 20 healthy cats. Echocardiography was the gold standard method for diagnosing heart disease. The results of seven methods were retrieved: (1) Vertebral heart score (VHS) with a cutoff value >8, (2) VHS with a cutoff value >8.5, (3) multiplication of cardiac length (L) and width (W), (4) multiplication of cardiac L and W divided by the L of the fourth sternal thoracic bone, (5) N-terminal Pro-B-type natriuretic peptide (NT-proBNP) point-of-care test, (6) subjective ultrasonographic assessment of the left atrial size, and (7) subjective radiographic assessment of the left atrial size. Cross-tabulation was used to calculate the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for each test. This study found that using the NT-proBNP point-of-care test was optimal in the diagnosis of cats with heart disease. RESULTS: The subjective ultrasonographic assessment of the left atrial size was good for diagnosing hypertrophic cardiomyopathy and congestive heart failure. CONCLUSION: This study showed that the more tests used, the higher the reliability of the diagnosis.