Cardiac Electromechanical Activity in Healthy Cats and Cats with Cardiomyopathies.

Optimal heart function depends on perfect synchronization between electrical and mechanical activity. In this pilot study, we aimed to investigate the electromechanical activity of the heart in healthy cats and cats with cardiomyopathy with phonocardiography (PCG) synchronized to an electrocardiography (ECG) pilot device. We included 29 cats (12 healthy cats and 17 cats diagnosed with cardiomyopathy) and performed a clinical examination, PCG synchronized with ECG and echocardiography. We measured the following durations with the pilot PCG device synchronized with ECG: QRS (ventricular depolarization), QT interval (electrical systole), QS1 interval (electromechanical activation time (EMAT)), S1S2 (mechanical systole), QS2 interval (electrical and mechanical systole) and electromechanical window (end of T wave to the beginning of S2). The measured parameters did not differ between healthy cats and cats with cardiomyopathy; however, in cats with cardiomyopathy, EMAT/RR, QS2/RR and S1S2/RR were significantly longer than in healthy cats. This suggests that the hypertrophied myocardium takes longer to generate sufficient pressure to close the mitral valve and that electrical systole, i.e., depolarization and repolarization, and mechanical systoles are longer in cats with cardiomyopathy. The PCG synchronized with the ECG pilot device proved to be a valuable tool for evaluating the electromechanical activity of the feline heart.

Evaluation of antioxidant status and lipid peroxidation in dogs with myxomatous mitral valve degeneration stage B1.

Myxomatous mitral valve degeneration (MMVD) is the most common naturally occurring heart disease in dogs. There is a lack of data on antioxidant status and oxidative damage in dogs with MMVD stage B1 according to the American College of Veterinary Internal Medicine (ACVIM B1). The aim of this study was to investigate antioxidant status (plasma vitamin E, lipid-standardized vitamin E (LS-VitE), antioxidant capacity of lipid-(ACL) and water-soluble antioxidants, whole blood glutathione peroxidase and erythrocyte superoxide dismutase), and lipid peroxidation [malondialdehyde (MDA)] in dogs with MMVD ACVIM B1. Serum cholesterol and triglyceride concentrations were measured to calculate LS-VitE. Fourteen dogs with MMVD ACVIM B1 and 12 control dogs were included in the study. Dogs with MMVD had significantly higher vitamin E, ACL, MDA, and cholesterol concentrations and significantly higher LS-VitE values than control dogs. No significant correlations between MDA and antioxidant parameters were determined in either group. In conclusion, oxidative damage to lipids is already present and the antioxidant status is altered but not depleted in dogs with MMVD ACVIM B1. The antioxidant response to increased oxidative damage consists mainly of the activation of fat-soluble antioxidants. Further research is needed to evaluate the efficacy and targets of early antioxidant supplementation to prevent or ameliorate oxidative stress and mitigate disease progression in dogs with early-stage MMVD.

Echocardiographic analysis of dogs before and after surgical treatment of brachycephalic obstructive airway syndrome.

Brachycephalic dogs with brachycephalic obstructive airway syndrome (BOAS) are a valuable animal model for obstructive sleep apnea (OSA) in humans. Clinical signs of upper airway obstruction improve after surgical treatment of BOAS, but the impact of surgery on morphology and function of the heart has not been studied. Therefore, we aimed to compare the echocardiographic variables of dogs before and after surgical treatment of BOAS. We included 18 client-owned dogs with BOAS (7 French Bulldogs, 6 Boston Terriers, and 5 Pugs) scheduled for surgical correction. We performed a complete echocardiographic examination before and 6 to 12 (median 9) months after surgery. Seven non-brachycephalic dogs were included in the control group. After surgery, BOAS patients had a significantly (p < 0.05) larger left atrium to aortic ratio (LA/Ao), left atrium in the long axis index, and thickness of the left ventricular posterior wall in diastole index. They also had a higher late diastolic annular velocity of the interventricular septum (Am) and increased global right ventricular strain and left ventricular global strain in the apical 4-chamber view, as well as a higher caudal vena cava collapsibility index (CVCCI). Before surgery, BOAS patients had a significantly lower CVCCI, Am, peak systolic annular velocity of the interventricular septum (Si), and early diastolic annular velocity of the interventricular septum (Ei) compared to non-brachycephalic dogs. After surgery, BOAS patients had a smaller right ventricular internal diameter at base index, right ventricular area in systole index, mitral annular plane systolic excursion index, and tricuspid annular plane systolic excursion index, as well as lower values of Am, Si, Ei, and late diastolic annular velocity of the interventricular septum, and a larger LA/Ao compared to non-brachycephalic dogs. Significant differences between BOAS patients and non-brachycephalic dogs indicate higher right heart pressures and decreased systolic and diastolic ventricular function in BOAS dogs, which is in accordance with the results of studies in OSA patients. In parallel with the marked clinical improvement, right heart pressures decreased, and right ventricular systolic and diastolic function improved after surgery.

Radiologic Evaluation of Portosystemic Shunts in Humans and Small Animals: Review of the Literature with Clinical Case Reports.

The portal venous system is a network of vessels that carry blood from the capillary beds of the major abdominal organs to the liver. During embryology, the portal venous system can develop aberrantly, leading to vascular connections between the portal and systemic venous circulation known as portosystemic shunts. The purpose of this comparative review with a few short representative case reports was to present the similarities and differences in portosystemic shunts in humans and small animals and their radiologic evaluation. Aberrant vascular connections between the portal and systemic venous circulation enable portal blood to bypass metabolism and detoxification in the liver, leading to significant clinical implications. Portosystemic shunts are very rare in humans, but these connections are much more common in small animals, affecting up to 0.6% of small animals. Portosystemic shunts can be congenital or acquired and are divided into intrahepatic and extrahepatic types. Because of its ability to accurately assess abdominal structures, large vessels, and their flow dynamics without anesthesia, ultrasonography has become the first imaging modality employed for the diagnostic evaluation of portosystemic shunts in both humans and small animals. This is usually followed by contrast-enhanced computed tomographic angiography in order to better define the exact shunt anatomy and to plan treatment. It is important to understand the embryology, anatomy, pathology, and pathophysiology of portosystemic shunts in order to understand the findings of radiologic imaging and to initiate appropriate treatment.

Effects of Coenzyme Q10 Supplementation on Oxidative Stress Markers, Inflammatory Markers, Lymphocyte Subpopulations, and Clinical Status in Dogs with Myxomatous Mitral Valve Disease.

Scarce data exist on the effects of coenzyme Q10 (CoQ10) supplementation in dogs with myxomatous mitral valve disease (MMVD). The purpose of this study was to investigate the effect of CoQ10 supplementation on oxidative stress markers (glutathione peroxidase, F2-isoprostanes), markers of inflammation (tumor necrosis factor-α, TNF soluble receptor II, leucocytes, and their subtypes), lymphocyte subpopulations (T helper and cytotoxic T lymphocytes, including activated T lymphocytes, and B lymphocytes), and echocardiographic and clinical parameters in dogs with MMVD. In this randomized, controlled, double-blind, longitudinal study, 43 MMVD dogs in stages ACVIM (American College of Veterinary Internal Medicine classification) B2 and ACVIM C and D (congestive heart failure (CHF)) received water-soluble coenzyme Q10 (100 mg twice daily) or placebo for 3 months, and 12 non-supplemented healthy dogs served as controls. All parameters were measured before and after supplementation in MMVD dogs and once in healthy dogs. CoQ10 supplementation had a positive impact on neutrophil percentage, lymphocyte percentage, and lymphocyte concentration in our cohort of dogs with CHF (ACVIM C and D). Conclusion: CoQ10 as an oral supplement may have benefits in terms of decreasing inflammation in dogs with MMVD and CHF.

Peripheral blood lymphocyte subtypes in dogs with different stages of myxomatous mitral valve disease.

BACKGROUND: Data on alterations in peripheral blood lymphocyte (PBL) subtypes in dogs with myxomatous mitral valve disease (MMVD) is lacking. OBJECTIVES: To investigate PBL subtypes and their correlation with parameters of inflammation and MMVD progression markers in dogs with different stages of MMVD. ANIMALS: Seventy-eight client-owned dogs: 65 with MMVD (American College of Veterinary Internal Medicine [ACVIM] classification stages B2, C, and D) and 13 healthy controls. METHODS: Prospective cross-sectional study. Complete cardiac assessment, flow cytometry (T lymphocytes [CD3+], their subtypes [CD3+CD4+, CD3+CD8+, CD3+CD4+CD8+, CD3+CD4-CD8-], and B lymphocytes [CD45+CD21+]) and measurement of N-terminal pro B-type natriuretic peptide, cardiac troponin I, and C-reactive protein concentrations were performed. RESULTS: The percentage of CD3+CD4+ lymphocytes was significantly lower in stable ACVIM C patients (P = .01) and unstable ACVIM C and D patients (P = .003), the percentage of CD3+CD8+ lymphocytes was significantly higher in stable ACVIM C patients (P = .01) and unstable ACVIM C and D patients (P = .01), CD3+CD8+ lymphocyte concentration was significantly higher in unstable ACVIM C and D patients (P = .05), and the CD3+CD4+/CD3+CD8+ ratio was significantly lower in stable ACVIM C patients (P = .01) and unstable ACVIM C and D patients (P = .01) compared with healthy controls. CONCLUSIONS AND CLINICAL IMPORTANCE: The percentages of CD3+CD4+ and CD3+CD8+ PBL and CD4+/CD8+ ratio were altered in MMVD dogs with congestive heart failure (ACVIM C, D), but not in ACVIM B2, suggesting involvement of these PBL subtypes in the pathogenesis of congestive heart failure in dogs with MMVD.

Inflammation and its association with oxidative stress in dogs with heart failure.

BACKGROUND: Inflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined. RESULTS: Thirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = - 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = - 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = - 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = - 0.436), interleukin-6 (P = 0.026, r = - 0.382), white blood cell (P = 0.032, r = - 0.369), neutrophil (P = 0.027, r = - 0.379) and monocyte counts (P = 0.024, r = - 0.386). CONCLUSION: Inflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.

Antioxidant capacity of lipid- and water-soluble antioxidants in dogs with subclinical myxomatous mitral valve degeneration anaesthetised with propofol or sevoflurane.

BACKGROUND: Antioxidants located in both the hydrophilic and lipophilic compartments of plasma act as a defence system against reactive oxygen species (ROS). Excessive production of ROS during anaesthesia affects the antioxidant capacity of plasma and may result in oxidative stress. The aim of this study was to evaluate the antioxidant capacity of lipid- (ACL) and water-soluble (ACW) antioxidants in client-owned dogs diagnosed with periodontal disease and early-stage myxomatous mitral valve degeneration (MMVD) and anaesthetised for a dental procedure with propofol and sevoflurane or with propofol only. RESULTS: Dogs with MMVD were anaesthetised with propofol and sevoflurane (MMVD/PS, n = 8) or with propofol only (MMVD/P, n = 10). Dogs with no evidence of MMVD (PS, n = 12) were anaesthetised with propofol and sevoflurane. Blood samples for determination of ACL and ACW were collected before and 5 min, 60 min and 6 h after induction to anaesthesia. In MMVD/PS dogs, ACL was significantly higher at all sampling times when compared to PS dogs. Compared to basal values, only anaesthesia maintained with propofol significantly increased ACL at 60 min in dogs with MMVD. In MMVD/P dogs, ACW increased after induction to anaesthesia and remained elevated up to 6 h after anaesthesia. Compared to basal values, anaesthesia maintained with sevoflurane significantly increased ACW only at 60 min in both dogs with and without MMVD. The only difference between propofol and propofol/sevoflurane anaesthesia in dogs with MMVD was significantly higher ACW at 60 min after induction to anaesthesia in the propofol group. CONCLUSIONS: Regarding antioxidant capacity, propofol could be a better choice than sevoflurane for anaesthesia of dogs with early-stage MMVD, although further studies are necessary to clarify the advantage of this antioxidant capacity.

Pulmonary Circulation Transvascular Fluid Fluxes Do Not Change during General Anesthesia in Dogs.

General anesthesia (GA) can cause abnormal lung fluid redistribution. Pulmonary circulation transvascular fluid fluxes (JVA ) are attributed to changes in hydrostatic forces and erythrocyte volume (EV) regulation. Despite the very low hydraulic conductance of pulmonary microvasculature it is possible that GA may affect hydrostatic forces through changes in pulmonary vascular resistance (PVR), and EV through alteration of erythrocyte transmembrane ion fluxes ( ionJVA ). Furosemide (Fur) was also used because of its potential to affect pulmonary hydrostatic forces and ionJVA . A hypothesis was tested that JVA , with or without furosemide treatment, will not change with time during GA. Twenty dogs that underwent castration/ovariectomy were randomly assigned to Fur (n = 10) (4 mg/kg IV) or placebo treated group (Con, n = 10). Baseline arterial (BL) and mixed venous blood were sampled during GA just before treatment with Fur or placebo and then at 15, 30 and 45 min post-treatment. Cardiac output (Q) and pulmonary artery pressure (PAP) were measured. JVA and ionJVA were calculated from changes in plasma protein, hemoglobin, hematocrit, plasma and whole blood ions, and Q. Variables were analyzed using random intercept mixed model (P < 0.05). Data are expressed as means ± SE. Furosemide caused a significant volume depletion as evident from changes in plasma protein and hematocrit (P < 0.001). However; Q, PAP, and JVA were not affected by time or Fur, whereas erythrocyte fluid flux was affected by Fur (P = 0.03). Furosemide also affected erythrocyte transmembrane K+ and Cl-, and transvascular Cl- metabolism (P ≤ 0.05). No other erythrocyte transmembrane or transvascular ion fluxes were affected by time of GA or Fur. Our hypothesis was verified as JVA was not affected by GA or ion metabolism changes due to Fur treatment. Furosemide and 45 min of GA did not cause significant hydrostatic changes based on Q and PAP. Inhibition of Na+/K+/2Cl- cotransport caused by Fur treatment, which can alter EV regulation and JVA , was offset by the Jacobs Stewart cycle. The results of this study indicate that the Jacobs Stewart cycle/erythrocyte Cl- metabolism can also act as a safety factor for the stability of lung fluid redistribution preserving optimal diffusion distance across the blood gas barrier.

Systemic inflammation in dogs with advanced-stage heart failure.

BACKGROUND: Although human studies have shown that inflammation plays a role in the development of congestive heart failure, scarce information exists on white blood cell count (WBC) and differential cell counts in various stages of heart failure in man and dogs. A few studies demonstrated increased concentrations of C-reactive protein (CRP), a major acute-phase protein, in cardiac diseases in dogs. Our research aimed to investigate whether CRP concentration, WBC and neutrophil count (NEUT), as markers of systemic inflammation, are elevated in canine cardiovascular patients. We also aimed to find out whether there is an association between CRP concentration and WBC and NEUT, as well as associations between these inflammatory markers and selected echocardiographic parameters. Sixty-two client-owned canine cardiac patients and 12 healthy dogs were included in the study. The patients were classified into International Small Animal Cardiac Health Council classes (ISACHC I-III). The serum CRP concentration was determined using a canine CRP test kit. WBC and NEUT were determined using an automated hematology analyzer. RESULTS: Significantly higher serum CRP concentration, WBC and NEUT were found in the decompensated stage of heart failure (ISACHC III) compared with healthy dogs and with patients in ISACHC group II and ISACHC group I. Serum CRP concentration significantly positively correlated with WBC (r = 0.65, P < 0.001) and NEUT (r = 0.58, P = 0.002) in the ISACHC III group, while no significant correlations were found in the ISACHC I and II groups. A significant negative correlation between serum CRP concentration and the left ventricular ejection fraction (r = - 0.49, P = 0.046) and a significant positive correlation between CRP and the E wave velocity of the mitral valve inflow (r = 0.52, P = 0.046) were found in the ISACHC III group. CONCLUSIONS: The CRP concentration, WBC and NEUT were significantly increased in advanced-stage heart failure patients in comparison with compensated patients and healthy dogs, which indicate the presence of systemic inflammation. However, normal CRP concentration and normal WBC and NEUT can also be present in heart failure.

Markers of oxidative stress in dogs with heart failure.

We tested the hypothesis that indirect measures of oxidative stress (vitamin E, glutathione peroxidase, and malondialdehyde) differ in dogs in heart failure resulting from either myxomatous mitral valve disease or dilated cardiomyopathy. Dogs were classified according to the International Small Animal Cardiac Health Council (ISACHC) classification. Additionally, the effect of cardiac therapy on oxidative stress parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in advanced stages of congestive heart failure was investigated. There were no significant differences in oxidative stress parameters between healthy dogs and the individual groups of cardiac patients. Significantly lower malondialdehyde (MDA) was observed in the ISACHC II group in comparison to ISACHC groups III and I. A significant positive correlation in treated patients was observed between NT-proBNP and MDA, NT-proBNP and vitamin E, as well as between MDA and vitamin E (and lipid-standardized vitamin E). No significant differences in any of the measured parameters were found between treated and non-treated cardiac patients. Our results suggest an association between MDA (the extent of lipid peroxidation) and NT-proBNP, vitamin E and NT-proBNP, as well as between MDA and vitamin E in treated canine patients. Plasma vitamin E concentration was maintained in all stages of cardiovascular disease in these canine patients.

Polycystic kidney disease: a review and occurrence in Slovenia with comparison between ultrasound and genetic testing.

Polycystic kidney disease (PKD) is an inherited autosomal kidney disease which is most commonly identified in Persian and Persian related cats. Positive cats have multiple cysts of various sizes that occur in the renal cortex and medulla and occasionally in other abdominal organs. PKD often leads to renal failure which occurs from mid to late in life. Renal cysts can be diagnosed ultrasonographically after 7 weeks of age by an experienced ultrasonographer and a high resolution machine. However, ultrasonography is now being replaced by genetic screening. A total of 340 cats of variable breeds aged from 5 months to 18 years were ultrasonographically examined in the past 7 years at the University Veterinary Small Animal Clinic. Of these, 13.8% were PKD positive with very high prevalence in Persian cats (36%). There was no sex predilection identified. The C>A transversion at position 3284 on exon 29 of PKD1 gene, resulting in a stop mutation has been identified in the heterozygous state in eight affected cats examined (Persian breed). All heterozygous cats were also ultrasonographically positive.

Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy.

OBJECTIVE: To evaluate the role of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 6 dogs with DCM, including 2 Doberman Pinschers, 2 Newfoundlands, and 2 Great Danes. PROCEDURE: All dogs had clinical signs of congestive heart failure, and a diagnosis of DCM was made on the basis of echocardiographic findings. Blood samples were collected from each dog, and genomic DNA was isolated by a salt extraction method. Specific oligonucleotides were designed to amplify the promoter, exon 1, the 5'-part of exon 2 including the complete coding region, and part of intron 1 of the canine phospholamban gene via polymerase chain reaction procedures. These regions were screened for mutations in DNA obtained from the 6 dogs with DCM. RESULTS: No mutations were identified in the promoter, 5' untranslated region, part of intron 1, part of the 3' untranslated region, and the complete coding region of the phospholamban gene in dogs with DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that mutations in the phospholamban gene are not a frequent cause of DCM in Doberman Pinschers, Newfoundlands, and Great Danes.

Characterization of the canine desmin (DES) gene and evaluation as a candidate gene for dilated cardiomyopathy in the Dobermann.

Canine-dilated cardiomyopathy (DCM) in dogs is a disease of the myocardium associated with dilatation and impaired contraction of the ventricles and is suspected to have a genetic cause. A missense mutation in the desmin gene (DES) causes DCM in a human family. Human DCM closely resembles the canine disease. In the present study, we evaluated whether DES gene mutations are responsible for DCM in Dobermann dogs. We have isolated bacterial artificial chromosome clones (BACs) containing the canine DES gene and determined the chromosomal location by fluorescence in situ hybridization (FISH). Using data deposited in the NCBI trace archive and GenBank, the canine DES gene DNA sequence was assembled and seven single nucleotide polymorphisms (SNPs) were identified. From the canine DES gene BAC clones, a polymorphic microsatellite marker was isolated. The microsatellite marker and four informative desmin SNPs were typed in a Dobermann family with frequent DCM occurrence, but the disease phenotype did not associate with a desmin haplotype. We concluded that mutations in the DES gene do not play a role in Dobermann DCM. Availability of the microsatellite marker, SNPs and DNA sequence reported in this study enable fast evaluation of the DES gene as a DCM candidate gene in other dog breeds with DCM occurrence.