Relationship of Plasma N‐terminal Pro‐brain Natriuretic Peptide Concentrations to Heart Failure Classification and Cause of Respiratory Distress in Dogs Using a 2nd Generation ELISA Assay

Background

Cardiac biomarkers provide objective data that augments clinical assessment of heart disease (HD).

Hypothesis/Objectives

Determine the utility of plasma N‐terminal pro‐brain natriuretic peptide concentration [NT‐proBNP] measured by a 2nd generation canine ELISA assay to discriminate cardiac from noncardiac respiratory distress and evaluate HD severity.

Animals

Client‐owned dogs (n = 291).

Methods

Multicenter, cross‐sectional, prospective investigation. Medical history, physical examination, echocardiography, and thoracic radiography classified 113 asymptomatic dogs (group 1, n = 39 without HD; group 2, n = 74 with HD), and 178 with respiratory distress (group 3, n = 104 respiratory disease, either with or without concurrent HD; group 4, n = 74 with congestive heart failure [CHF]). HD severity was graded using International Small Animal Cardiac Health Council (ISACHC) and ACVIM Consensus (ACVIM‐HD) schemes without knowledge of [NT‐proBNP] results. Receiver‐operating characteristic curve analysis assessed the capacity of [NT‐proBNP] to discriminate between dogs with cardiac and noncardiac respiratory distress. Multivariate general linear models containing key clinical variables tested associations between [NT‐proBNP] and HD severity.

Results

Plasma [NT‐proBNP] (median; IQR) was higher in CHF dogs (5,110; 2,769–8,466 pmol/L) compared to those with noncardiac respiratory distress (1,287; 672–2,704 pmol/L; P < .0001). A cut‐off >2,447 pmol/L discriminated CHF from noncardiac respiratory distress (81.1% sensitivity; 73.1% specificity; area under curve, 0.84). A multivariate model comprising left atrial to aortic ratio, heart rate, left ventricular diameter, end‐systole, and ACVIM‐HD scheme most accurately associated average plasma [NT‐proBNP] with HD severity.

Conclusions and Clinical Importance

Plasma [NT‐proBNP] was useful for discriminating CHF from noncardiac respiratory distress. Average plasma [NT‐BNP] increased significantly as a function of HD severity using the ACVIM‐HD classification scheme.     

Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low‐Dose Aspirin

Background

Low‐dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are nonresponsive to the antiplatelet effects of aspirin (“aspirin resistance”).

Hypothesis/Objectives

That low‐dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression.

Animals

Twenty‐four healthy dogs.

Methods

A repeated measures study. Platelet function (PFA‐100 closure time, collagen/epinephrine), platelet COX‐1 and COX‐2 expression, and urine 11‐dehydro‐thromboxane B₂ (11‐dTXB₂) were evaluated before and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, nonresponders, and inconsistent responders.

Results

Low‐dose aspirin increased closure times significantly (62% by Day 10, P < .001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX‐1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, ?29.7–136.1%) (P = .047) and 72% on Day 10 (range, ?0.37–210%) (P < .001). Platelet COX‐2 MFI increased significantly by 34% (range, ?29.2–270%) on Day 3 (P = .003) and 74% (range, ?19.7–226%) on Day 10 (P < .001). Urinary 11‐dTXB₂ concentrations significantly (P = .005, P < .001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production.

Conclusions and Clinical Importance

Low‐dose aspirin consistently inhibits platelet function in approximately one‐third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. COX isoform expression before treatment did not predict aspirin resistance.

     

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment

Background

Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA.

Objective

Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism.

Animals

Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled.

Methods

cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA.

Results

cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01–0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0‐2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5‐3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3‐3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2–4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation.

Conclusions and Clinical Relevance

Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.     

Evaluation of the Cortisol‐to‐ACTH Ratio in Dogs with Hypoadrenocorticism,Dogs with Diseases Mimicking Hypoadrenocorticism and in Healthy Dogs

Background

The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods.

Objectives

To prospectively evaluate the cortisol‐to‐ACTH ratio (CAR) as a screening test for diagnosing canine HA.

Animals

Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs.

Methods

Plasma ACTH and baseline cortisol concentrations were measured before IV administration of 5 μg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium‐to‐potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under the ROC curve.

Results

The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA (P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA (ROC AUC 0.998), followed by the ACTH concentration (ROC AUC 0.97), baseline cortisol concentration (ROC AUC 0.96), and SPR (ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively.

Conclusion and Clinical Importance

Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA.     

Systematic Review of Evidence Relating to the Treatment of Immune‐Mediated Hemolytic Anemia in Dogs

Despite being the most prevalent autoimmune disease of dogs, there is considerable variation between individuals and institutions in the treatment regimens that are employed for the management of immune‐mediated hemolytic anemia. The aim of this review was to evaluate evidence relating to the treatment of the disease systematically and to use this evidence to draw conclusions that are applicable in wider veterinary practice. Search tools were employed to identify relevant articles and these were assessed according to stated criteria. The overall quality of published evidence was poor, with many articles failing to provide details of the enrollment, treatment, monitoring, and assessment stages of the study process. In view of this, firm conclusions cannot be drawn regarding the treatment of this disease and further research of a higher quality is required.     

Canine Pancreatic‐Specific Lipase Concentrations in Dogs with Heart Failure and Chronic Mitral Valvular Insufficiency

Background

Chronic mitral valvular insufficiency (CMVI) in dogs is very common and might cause clinical signs of congestion and poor tissue perfusion.

Hypothesis

Poor tissue perfusion from CMVI causes pancreatitis in dogs, as indicated by serum pancreatic lipase concentrations.

Animals

Sixty‐two client‐owned dogs consisting of 40 dogs with different stages of heart failure from CMVI and 22 age‐matched healthy dogs, based on full cardiac exam and routine laboratory tests.

Methods

Prospective, controlled, observational study. Serum canine pancreatic lipase immunoreactivity (cPLI) concentrations were determined by quantitative cPLI test in healthy and CMVI groups.

Results

Serum cPLI concentrations were 54.0 μg/L (IQR: 38.0–78.8 μg/L) in control, 55.0 μg/L (IQR: 38.3–88.8 μg/L) in ISACHC I, 115.0 μg/L (IQR: 45.0–179.0 μg/L) in ISACHC II and 223.0 μg/L (IQR: 119.5–817.5 μg/L) in ISACHC III. Close correlation to serum cPLI concentration was found in the left atrial to aorta (LA/Ao) ratio (r = 0.597; P = .000) and the severity of heart failure (r = 0.530; P = .000).

Conclusions and Clinical Importance

This study found CMVI is associated with pancreatic injury in congestive heart failure caused by CMVI. Therefore, periodic monitoring on cPLI could be useful in monitoring dogs in heart failure.     

Comparatively examining of the apelin‐13 levels in the Capoeta trutta (Heckel, 1843) and Cyprinus carpio (Linnaeus, 1758)

Apelin is a recently discovered peptide produced by several tissues in the various vertebrates and fish. Apelin has been suggested to have role in regulation of many diverse physiological functions including food intake, energy homoeostasis, immunity, osmoregulation and reproduction. In this study, apelin‐13 levels in the blood serum of Cyprinus carpio and Capoetta trutta were determined. Then the results were compared between two species and sexes of each species. Apelin‐13 level was analysed using the enzyme‐linked immunoassay (ELISA) kit (Rat apelin‐13 ELISA kit, catalog no: CSB‐E14367r). Apelin‐13 level in the blood serum of C. trutta was significantly higher than those of the C. carpio (p < 0.05). However, its levels were observed to be no significant difference (p > 0.05) that compared to between sexes of each species. There was a significant negative correlation (r = ?0.829, p = 0.0001) between the apelin‐13 level and body weight of C. carpio. However, no significant correlation (r = ?0.022, p = 0.924) between the apelin‐13 level and weight of C. trutta observed.