The diagnostic relevance of NT‐proBNP and proANP 31–67 measurements in staging of myxomatous mitral valve disease in dogs

Background

There is no agreement in current publications regarding the reliability of serum concentrations of natriuretic peptides (NPs) to detect dogs with subclinical myxomatous mitral valve disease (MMVD) and to differentiate between asymptomatic stages.

Objectives

We sought to compare N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and pro‐atrial natriuretic peptide 31‐67 (proANP) concentrations between various stages of canine MMVD and to investigate the influence of age, weight, and sex.

Methods

In this prospective study, dogs were classified in different disease stages using the modified Canine Heart failure International Expert Forum (CHIEF) system. Serum NP concentrations were compared between groups.

Results

A total of 559 samples from 116 healthy dogs and 236 dogs with MMVD were analyzed. Using cut‐off values (1207 pmol/L for NT‐proBNP, 1578 fmol/mL for proANP), dogs with MMVD with and without congestive heart failure (CHF) could be differentiated with a sensitivity of 83% for both and specificities of 85% and 86%, respectively. Dogs staged in CHIEF B1 and B2 could not be distinguished based on NP concentrations due to wide variation within the groups. Intact females (means 598 pmol/L and 1036 fmol/mL, respectively) had significantly higher values of both NPs than intact males (315 pmol/L and 836 fmol/mL).

Conclusions

NPs in canine MMVD are useful to discriminate between asymptomatic dogs and dogs with CHF. Due to a large overlap of NP‐concentrations between the groups, NPs do not seem to be useful to differentiate between dogs in stages B1 and B2. Interpretation of NT‐proBNP and proANP values should include consideration of sex‐specific differences.     

Lowered N-terminal pro-B-type natriuretic peptide levels in response to treatment predict survival in dogs with symptomatic mitral valve disease

ObjectivesIn humans with congestive heart failure (CHF), better outcome is correlated with lower natriuretic peptide (NP) levels after starting treatment and greater percentage reduction of NP levels. Therefore, the aim of this study was to determine the relationship between absolute and relative changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and pro-atrial natriuretic peptide 31–67 (proANP 31–67) and overall cardiac survival in patients with symptomatic myxomatous mitral valve disease (MMVD). Furthermore, we sought to compare clinical and echocardiographic status of 12-month survivors and non-survivors.Animals, materials and methods26 dogs with CHF due to MMVD. Initial NP levels, as well as absolute and percentage changes of follow-up NP levels (between 7 and 30 days after treatment start) and heart failure (HF) class were tested as potential predictors of overall cardiac survivorship. Additionally, various echocardiographic parameters, creatinine concentrations and furosemide doses were compared between 12-month survivors and non-survivors.ResultsDogs with follow-up NT-proBNP level <965 pmol/l had a significantly longer overall cardiac survival than patients with NT-proBNP level >965 pmol/l (P = 0.03). Dogs in a higher HF class had a significantly (P = 0.03) higher probability of shorter survival independent of their NP levels. When dogs were grouped by 12-month survival, only follow-up NT-proBNP levels were significantly different between groups.ConclusionsHF class at presentation and NT-proBNP levels after initiating treatment are predictive of mortality in patients with symptomatic MMVD. ProANP 31–67 levels, percentage reduction in NPs levels, creatinine or urea concentration, echocardiographic parameters and furosemide dose did not predict outcome.     

Noninvasive Clinical Assessment of Systolic Torsional Motions by Two‐Dimensional Speckle‐Tracking Echocardiography in Dogs with Myxomatous Mitral Valve Disease

Background

Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two‐dimensional speckle‐tracking echocardiography (2D‐STE) in dogs with myxomatous mitral valve disease (MMVD) has not been reported.

Hypothesis

Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods.

Animals

Sixty‐seven client‐owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight‐ and age‐matched healthy dogs.

Methods

Dogs were examined for myocardial deformations by 2D‐STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate.

Results

Peak systolic torsion was higher in class II than in class I (P < .001) dogs. Peak systolic torsion was lower in class III than in class II (P = .001) dogs and controls (P = .003).

Conclusions and Clinical Importance

Torsional deformations assessed by 2D‐STE differed among clinical classes of MMVD. Myocardial torsional deformations by 2D‐STE may provide more detailed assessment of contractile function in dogs with MMVD.     

Plasma and platelet serotonin concentrations in healthy dogs and dogs with myxomatous mitral valve disease

ObjectivesSerotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD.Animals43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23).Methods5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA).ResultsMedian plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/10⁹ platelets and 176.6 ng/10⁹ platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration.ConclusionsCirculating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different.     

Cardiac Troponin‐I Concentration,Myocardial Arteriosclerosis,and Fibrosis in Dogs with Congestive Heart Failure because of Myxomatous Mitral Valve Disease

Background

Few previous studies have investigated the association between biomarkers and cardiac disease findings in dogs with naturally occurring myxomatous mitral valve disease (MMVD).

Aim

To investigate if histopathological changes at necropsy could be reflected by in vivo circulating concentrations of cTnI and aldosterone, and renin activity, in dogs with naturally occurring congestive heart failure because of MMVD.

Animals

Fifty privately owned dogs with MMVD and heart failure.

Methods

Longitudinal Study. Dogs were prospectively recruited and examined by clinical and echocardiographical examination twice yearly until time of death. Blood was stored for batched analysis of concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a standardized necropsy protocol.

Results

cTnI were associated with echocardiographic left ventricular end‐diastolic dimension (P < .0001) and proximal isovolumetric surface area radius (P < .004). Furthermore, in vivo cTnI concentrations reflected postmortem findings of global myocardial fibrosis (P < .001), fibrosis in the papillary muscles (P < .001), and degree of arterial luminal narrowing (P < .001) Aldosterone or renin activity did not reflect any of the cardiac disease variables investigated.

Conclusion and clinical importance

Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases.     

Effect of sampling time on urinary electrolytes following oral furosemide administration in dogs with myxomatous mitral valve disease

Introduction/ObjectivesUrine chemistry has received growing attention to estimate the diuretic response in dogs with cardiac disease.The aim of the study was to evaluate the impact of time elapsed between the oral furosemide administration and sample collection on urine chemistry in dogs with myxomatous mitral valve disease (MMVD) receiving diuretic therapy in American College of Veterinary Internal Medicine (ACVIM) stage C.Materials and methodsSeventy-three dogs with MMVD ACVIM stage C and 106 healthy dogs were prospectively included. Dogs with MMVD were divided, based on the time of sampling, in morning group (MMVD-MG) of one to 6 h and an evening group (MMVD-EG) over 6 h from oral furosemide administration. Analogously, healthy dogs sampled between 9 a.m. and 1 p.m. and between 2 and 7 p.m. were divided in a morning group (H-MG) and an evening group (H-EG), respectively. Urine chemistry, including fractional excretion of electrolytes, was evaluated and compared among groups.ResultsHigher excretion of sodium and chloride and higher urine sodium to urine potassium ratio (uNa⁺:uK⁺) were detected in MMVD-MG than MMVD-EG (P = 0.021, P = 0.038, and P = 0.016, respectively). Natriuresis, chloriuresis, and uNa⁺:uK+ were higher in MMVD-MG than H-MG, while no differences were found in the comparison between H-MG and H-EG and between MMVD-EG and H-EG.ConclusionsUrinary electrolyte excretion is significantly increased within 6 h from furosemide administration in MMVD ACVIM stage C dogs. Time of sampling from furosemide administration significantly affects urine chemistry in MMVD dogs and should be considered in clinical practice and the research field.     

Effect of N‐Acetylcysteine Supplementation on Intracellular Glutathione,Urine Isoprostanes,Clinical Score,and Survival in Hospitalized Ill Dogs

Background

Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes.

Hypothesis/Objectives

Supplementing dogs with N‐acetylcysteine (NAC) during the first 48 hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness.

Animals

Sixty systemically ill hospitalized client‐owned dogs and 14 healthy control dogs.

Methods

Randomized investigator‐blinded, placebo‐controlled prospective study. Dogs were randomized to treatment with NAC (n = 30) versus placebo (n = 30). Antioxidants, urine 8‐isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high‐performance liquid chromatography. Atomic absorption spectroscopy and enzyme‐linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively.

Results

Ill dogs had significantly lower vitamin E concentrations (27 versus 55 μg/mL; P = .0005) as well as elevated IP/Cr ratios (872 versus 399 pg/mg; P = .0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1 μM; P < .0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44 mM; P = .0463). Illness severity and survival were unchanged after short duration NAC supplementation.

Conclusions

Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48 hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.     

Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers

IntroductionScreening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable.ObjectiveTo investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP.Animals, materials and methodsAll dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived.ResultsHeart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo.ConclusionsBoth NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.     

Partial external mitral annuloplasty in dogs with myxomatous mitral valve degeneration and congestive heart failure: Outcome in 9 cases

Objective

To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD).

Animals, materials and methods

Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery.

Results

Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09).

Conclusions

Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.     

Risk Factors for Coughing in Dogs with Naturally Acquired Myxomatous Mitral Valve Disease

Background

Cough often is reported as the primary clinical sign of congestive heart failure (CHF) in dogs with chronic degenerative myxomatous mitral valve disease (MMVD). Concurrent airway disease and compression of the left mainstem bronchus by a large left atrium also have been proposed as potential causes of coughing in these patients.

Objectives

To investigate the association between the presence of coughing and different potential causes of cough, including CHF, abnormal radiographic airway pattern, and cardiomegaly in dogs affected by naturally acquired MMVD.

Animals

Two hundred six client‐owned dogs.

Methods

Retrospective analysis performed on medical records of dogs affected by MMVD that underwent full cardiac evaluation, including echocardiographic examination and thoracic radiography.

Results

Univariate analyses showed that CHF is not a predictor of coughing (OR = 1.369; 0.723, 2.594), whereas abnormal radiographic airway pattern (OR = 3.650; 2.051, 6.496) and increased left atrial size observed radiographically (OR = 3.637; 1.904, 6.950) or echocardiographically (OR = 2.553; 1.436, 4.539) were significantly associated with coughing in dogs with MMVD. The same risk factors were significant in multivariate analyses.

Conclusions and Clinical Importance

This study indicates that CHF is not significantly associated with coughing in dogs with MMVD. Instead, abnormal radiographic airway pattern and left atrial enlargement are associated with coughing in these patients. This important finding should be taken into account when considering diagnosis and clinical management of CHF in these dogs.     

Prediction of clinically important acquired cardiac disease without an echocardiogram in large breed dogs using a combination of clinical,radiographic and electrocardiographic variables

IntroductionLarge breed (LB) dogs develop dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD). Echocardiography is required for a definitive diagnosis but is not always available. Our objective was to assess the clinical utility of thoracic radiographs alone and in combination with physical examination and electrocardiography findings for the prediction of clinically important DCM or MMVD in LB dogs.AnimalsFour hundred fifty-five client-owned dogs ≥20 kg with concurrent thoracic radiographs and echocardiogram.Materials and methodsMedical records were reviewed and stored thoracic radiographs and echocardiographic images were measured to classify dogs as normal heart size (NHS), preclinical DCM, clinical DCM, preclinical MMVD (with cardiomegaly), clinical MMVD, or equivocal. Dogs with preclinical MMVD, without cardiomegaly, were classified as NHS. Vertebral heart size (VHS) and vertebral left atrial size (VLAS) were measured. Receiver operating characteristic curves and prediction models were derived.ResultsPrevalence of MMVD (39.3%) was higher than the prevalence of DCM (24.8%), though most MMVD dogs (67.0%) lacked cardiomegaly and were classified as NHS for analysis. The area under the curve for VHS to discriminate between NHS and clinical DCM/MMVD or preclinical DCM/MMVD was 0.861 and 0.712, respectively, while for VLAS, it was 0.891 and 0.722, respectively. Predictive models incorporating physical examination and electrocardiography findings in addition to VHS/VLAS increased area under the curve to 0.978 (NHS vs. clinical DCM/MMVD) and 0.829 (NHS vs. preclinical DCM/MMVD).ConclusionsThoracic radiographs were useful for predicting clinically important DCM or MMVD in LB dogs, with improved discriminatory ability when physical examination abnormalities and arrhythmias were accounted for.     

Glutathione Peroxidase Activity,Plasma Total Antioxidant Capacity,and Urinary F2‐ Isoprostanes as Markers of Oxidative Stress in Anemic Dogs

Background

Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at‐risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated.

Hypothesis/Objective

Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15‐F₂‐isoprostanes (F₂‐IsoP) when compared to healthy dogs.

Animals

40 client‐owned dogs with anemia (PCV <30%) age‐matched to 40 client‐owned healthy control dogs.

Methods

Prospective, cross‐sectional study. Whole blood GPx activity, plasma TAC, and urinary F₂‐isoprostane concentrations were evaluated in each dog and compared between groups.

Results

Anemic dogs had significantly lower GPx activity (43.1 × 10³ +/‐ 1.6 × 10³ U/L) than did dogs in the control group (75.8 × 10³ +/‐ 2.0 × 10³ U/L; P < 0.0001). The GPx activity in dogs with hemolysis (10³ +/‐ 0.8 × 10³ U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 10³ +/‐ 1.1 × 10³ U/L). The TAC concentrations (P = 0.15) and urinary F₂‐isoprostanes (P = 0.73) did not significantly differ between groups.

Conclusions and Clinical Importance

Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs.     

The effect of select seminal plasma proteins on endometrial mRNA cytokine expression in mares susceptible to persistent mating‐induced endometritis

In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating‐induced endometritis PMIE Select seminal plasma proteins cysteine‐rich secretory protein‐3 (CRISP‐3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP‐3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ml CRISP‐3, 150 μg/ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 × 10⁹ spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro‐inflammatory cytokines interleukin (IL)‐1β, IL‐8, tumour necrosis factor (TNF)‐α, interferon (INF)‐γ, anti‐inflammatory cytokines IL‐1RN and IL‐10, and inflammatory‐modulating cytokine IL‐6). Seminal plasma treatment increased the mRNA expression of IL‐1β (p = .019) and IL‐8 (p = .0068), while suppressing the mRNA expression of TNF (p = .0013). Lactoferrin also suppressed the mRNA expression of TNF (p = .0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro‐inflammatory response seen in susceptible mares.     

Assessment of global and regional left ventricular volume and shape by real-time 3-dimensional echocardiography in dogs with myxomatous mitral valve disease

Background: Left ventricular (LV) remodeling occurs in response to chronic volume overload. Real‐time 3‐dimensional (RT3D) echocardiography offers new modalities for LV assessment. Objective: To investigate LV changes in shape and volume in response to different severities of naturally acquired myxomatous mitral valve disease (MMVD) in dogs by RT3D echocardiography. Animals: Sixty‐five client‐owned dogs. Methods: Prospectively recruited dogs were classified by standard echocardiography into healthy, mild, moderate, and severe MMVD groups. Endocardial border tracking of LV RT3D dataset was performed, from which global and regional (automatically acquired basal, mid, and apical segments based on LV long‐axis length) end‐diastolic (EDV) and end‐systolic volumes (ESV), LV long‐axis length, and sphericity index were obtained. Results: Global and regional EDV and ESV (indexed to body weight) were most prominently increased in dogs with severe MMVD. All 3 regional LV segments contributed to increased global EDV and ESV with increasing MMVD severity, but mid‐EDV contributed the most to the global EDV increase. Furthermore, LV long‐axis length and LV sphericity index increased with increasing MMVD severity. Basal and apical EDV segments displayed the strongest association with sphericity index (P < .0001). Conclusions and Clinical Importance: The most prominent LV volume expansion was found in dogs with severe MMVD. Increased EDV, primarily in the mid‐segment, leads to rounding of LV apical and basal segments in response to increasing MMVD severity. Assessment of LV volume and shape potentially could allow early detection of dogs at risk for rapid progression into congestive heart failure.     

Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with Myxomatous Mitral Valve Disease

Background

Right ventricular (RV) dysfunction independently predicts outcomes in human myxomatous mitral valve disease (MMVD). There is limited information regarding RV systolic function in dogs with MMVD.

Hypothesis

Right ventricular systolic function differs among stages of disease, decreasing in decompensated MMVD.

Animals

Thirty‐sixclient‐owned dogs with MMVD not receiving oral cardiovascular medications.

Methods

Prospective clinical study. Dogs were categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven echocardiographic indices of RV systolic function were measured. Groups were compared by 1‐way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac remodeling falling outside previously established reference intervals were compared using Fisher's exact test. Intra‐ and interobserver measurement variability was calculated for each RV function index.

Results

The indices TAPSE (P = 0.029), RV St_L (P = 0.012), and RV StR_L (P = 0.041) were significantly different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs (P = 0.027). Measurement variability of TAPSE, RV S', and RV St_G was clinically acceptable.

Conclusions and Clinical Importance

Right ventricular systolic function differs between stages of MMVD, increasing in stage B2, and declining in stage C. The prognostic importance of RV function indices, particularly TAPSE, might be worth evaluating in dogs with MMVD.     

Total antioxidant capacity and protein peroxidation intensity in seminal plasma of infertile and fertile dogs

The aim of this study was to evaluate the total antioxidant capacity and protein peroxidation intensity in seminal plasma of infertile and fertile dogs. The study was conducted on 10 infertile and 10 fertile dogs of various breeds. Infertility was defined as conception failure at least three matings with different bitches. Semen was collected by manual manipulation. The sperm concentration and motility parameters were evaluated using CASA Hamilton Thorne, Vers. IVOS 12.3. The morphology of spermatozoa and the percentage of live and dead sperm cells were assessed microscopically, total antioxidant capacity and the content of SH‐groups in seminal plasma were determined spectrophotometrically, the contents of protein peroxidation markers in seminal plasma, bityrosine and formylokinurenine, were determined using spectrofluorimetric methods. Sperm concentration and total sperm count were significantly (p < 0.05) lower in infertile dogs than in fertile dogs (99.92 ± 3 0.05 × 10⁶/ml vs. 282.07 ± 48.27 × 10⁶/ml; 214.19 ± 114.74 × 10⁶ vs. 747.57 ± 210.94 × 10⁶, respectively). The percentage of spermatozoa with normal morphology and the most determined motility parameters differed significantly (p < 0.05) between both groups. The mean values of total antioxidant capacity in the seminal plasma were significantly (p < 0.05) lower (19.95 ± 20.94 vs. 25.66 ± 23.18 µmol/g protein), whereas the mean contents of bityrosine and formylokinurenine in seminal plasma were significantly (p < 0.05) higher in infertile dogs than in fertile dogs (3.71 ± 4.83 µg/mg protein vs. 1.55 ± 2.00 µg/mg protein and 0.37 ± 0.45 µg/mg protein vs. 0.14 ± 0.08 µg/mg protein, respectively). In conclusion, the obtained results suggest that the poor semen quality and infertility in dogs could be associated with lowered total antioxidant capacity and increased protein peroxidation in seminal plasma as a consequence of oxidative stress.     

Serial determination of biomarkers of oxidative stress and antioxidant status in dogs with naturally occurring gastric dilatation-volvulus

Objective: To serially determine the biomarkers of oxidative stress and antioxidant status of dogs with gastric dilatation‐volvulus (GDV) over 48 hours. Design: Prospective study. Setting: Veterinary teaching hospital intensive care unit. Animals: Thirteen client‐owned dogs with GDV. Interventions: None. Measurement and main results: For all dogs, biomarkers of oxidative stress and antioxidant status were ascertained. Indicators of oxidative stress measured included F_2α‐isoprostanes (isoprostanes) and malondialdehyde (MDA). Vitamin C, vitamin E, glutathione peroxidase (GSHPx), and oxygen radical absorbance capacity (ORAC) were measured to assess antioxidant status. Oxidants and antioxidants were measured at the time of admission and at 24 and 48 hours post‐admission. There were significant decreases in vitamin E (P=0.002), vitamin C (P=0.001), ORAC (P=0.02), and MDA (P=0.001) during hospitalization. There was no significant change in GSHPx and isoprostane concentrations over time. Conclusion: Oxidative stress and antioxidant capacity in dogs with GDV change over time. Further studies measuring oxidative stress in more severely affected dogs and performing measurements earlier in the disease process may be beneficial in determining when oxidative stress is most severe during the course of GDV management.     

Detection of Congestive Heart Failure in Dogs by Doppler Echocardiography

Background: Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. Hypothesis: CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). Animals: Sixty‐three client‐owned dogs. Methods: Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver‐operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. Results: Presence of CHF secondary to MVD or DCM could best be predicted by E : isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P < .001), respiration rate (AUC=0.94, P < .001), Diastolic Functional Class (AUC=0.93, P < .001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R²=0.80, P < .001) or Diastolic Functional Class (AUC=1.00, P < .001), respiration rate (AUC=1.00, P < .001), and E : IVRT (AUC=0.99, P < .001), and a combination of Diastolic Functional Class and E : IVRT (R²=0.94, P < .001), respectively, whereas other variables including N‐terminal pro‐brain natriuretic peptide, E : Ea, and E : Vp were less useful. Conclusion and Clinical Importance: Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.     

Predictive value of natriuretic peptides in dogs with mitral valve disease

Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination and the status of the dogs 5 years after the initial examination was determined by telephone calls to the owner. All dogs were evaluated by clinical examination and echocardiography. CKCS with severe MR had higher NT-proANP and NT-proBNP compared to controls and CKCS with less severe MR. Dogs with clinical signs of HF had markedly elevated NT-proANP and NT-proBNP. Plasma concentrations of the natriuretic peptides measured at re-examination could predict progression in regurgitant jet size.     

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.