Prospective study of dilated cardiomyopathy in dogs eating nontraditional or traditional diets and in dogs with subclinical cardiac abnormalities

BackgroundRecent studies have investigated dogs with presumed diet‐associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed.Hypothesis/ObjectivesTo evaluate baseline features and serial changes in echocardiography and cardiac biomarkers in dogs with DCM eating nontraditional diets (NTDs) or traditional diets (TDs), and in dogs with subclinical cardiac abnormalities (SCA) eating NTD.AnimalsSixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs.MethodsEchocardiography, electrocardiography, and measurement of taurine, cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide were performed in dogs with DCM or SCA. Diets were changed for all dogs, taurine was supplemented in most, and echocardiography and cardiac biomarkers were reassessed (3, 6, and 9 months).ResultsAt enrollment, there were few differences between dogs with DCM eating NTDs or TDs; none had low plasma or whole blood taurine concentrations. Improvement in fractional shortening over time was significantly associated with previous consumption of a NTD, even after adjustment for other variables (P = .005). Median survival time for dogs with DCM was 611 days (range, 2‐940 days) for the NTD group and 161 days (range, 12‐669 days) for the TD group (P = .21). Sudden death was the most common cause of death in both diet groups. Dogs with SCA also had significant echocardiographic improvements over time.Conclusions and Clinical ImportanceDogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes.     

Detection of blood‐brain barrier dysfunction using advanced imaging methods to predict seizures in dogs with meningoencephalitis of unknown origin

BackgroundThe blood‐brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability.Hypothesis/ObjectivesPermeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures.AnimalsForty dogs with MUO and 12 dogs without MUO.MethodsRetrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively.ResultsDogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%.Conclusions and Clinical ImportanceImaging‐based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO.     

Etiology and outcome of extreme neutrophilic leukocytosis: A multi‐institutional retrospective study of 269 dogs

BackgroundThe magnitude of diagnostic abnormalities can influence the perception of clinical outcome. Extreme neutrophilic leukocytosis (ENL) is an uncommon finding caused by markedly increased granulopoiesis. A lack of recent, large‐scale studies limits our understanding of the importance, causation, and prognosis associated with ENL in dogs.Hypothesis/ObjectivesDescribe disease categories (DC) identified in dogs with ENL and identify variables associated with survival. We hypothesized that factors including fever, segmented and band neutrophil counts, and DC would be negatively associated with survival.AnimalsTwo‐hundred sixty‐nine dogs with ENL (segmented neutrophils ≥50 × 10³ cells/μL) presented to the veterinary teaching hospitals at Auburn University (n = 164), the University of Missouri (n = 81), and Oklahoma State University (n = 24) between January 1, 2009 and December 31, 2019.MethodsRetrospective study. Demographic data and outcome variables including temperature, CBC findings, DC, duration of hospitalization (DOH) and outcome were acquired from the medical record. Statistical analyses included chi‐squared and Kruskal‐Wallis tests, and Pearson product moment correlations with a P < .05 significance level.ResultsMortality was 41%. Survival differed with DC (P = .002). Mortality was higher (P < .05) in dogs with neoplasia (56.2%) vs immune‐mediated disease (20.5%) or tissue damage/necrosis (19%). Weight (P = .001, r = −0.14) and total neutrophil count (P = .04, r = −0.02) were weakly negatively associated with survival whereas DOH was weakly positively associated with survival (P = .03, r = 0.14).Conclusions and Clinical ImportanceMortality in dogs with ENL is high but differed according to DC. Only weak correlations between clinical or clinicopathologic variables and mortality were identified. Extreme neutrophilic leukocytosis should be interpreted in conjunction with the underlying disease process, and not broadly used to predict clinical outcome.     

Clinical,Pathologic, and Immunohistochemical Prognostic Factors in Dogs with Thyroid Carcinoma

Background

Prognostic markers for dogs with thyroid tumors are limited.

Hypothesis/Objectives

To identify clinical, pathologic, and immunohistochemical prognostic factors for dogs with thyroid tumors.

Animals

Seventy dogs with thyroid neoplasia.

Methods

Retrospective study. Dogs with thyroid neoplasia were included when follow‐up information and formalin‐fixed paraffin‐embedded tumor samples were available. Immunohistochemistry (IHC) was performed for thyroglobulin, calcitonin, Ki‐67, and E‐cadherin. Correlation of tumor variables (diameter, volume, localization, scintigraphic uptake, thyroid function, IHC) with local invasiveness and metastatic disease was performed on all tumor samples. Forty‐four dogs treated by thyroidectomy were included in a survival analysis.

Results

Fifty dogs (71%) had differentiated follicular cell thyroid carcinoma (dFTC) and 20 (29%) had medullary thyroid carcinoma (MTC). At diagnosis, tumor diameter (P = .007; P = .038), tumor volume (P = .020), tumor fixation (P = .002), ectopic location (P = .002), follicular cell origin (P = .044), and Ki‐67 (P = .038) were positively associated with local invasiveness; tumor diameter (P = .002), tumor volume (P = .023), and bilateral location (P = .012) were positively associated with presence of distant metastases. Forty‐four dogs (28 dFTC, 16 MTC; stage I–III) underwent thyroidectomy. Outcome was comparable between dogs with dFTC and MTC. Macroscopic (P = .007) and histologic (P = .046) vascular invasion were independent negative predictors for disease‐free survival. Although time to presentation, histologic vascular invasion and Ki‐67 were negatively associated with time to metastases, and time to presentation was negatively associated with time to recurrence, no independent predictors were found. E‐cadherin expression was not associated with outcome.

Conclusions and Clinical Importance

Prognostic factors have been identified that provide relevant information for owners and clinicians.     

Comparison of lung ultrasound,chest radiographs,C‐reactive protein,and clinical findings in dogs treated for aspiration pneumonia

BackgroundComparison of clinical findings, chest radiographs (CXR), lung ultrasound (LUS) findings, and C‐reactive protein (CRP) concentrations at admission and serial follow‐up in dogs with aspiration pneumonia (AP) is lacking.HypothesisLung ultrasound lesions in dogs with AP are similar to those described in humans with community‐acquired pneumonia (comAP); the severity of CXR and LUS lesions are similar; normalization of CRP concentration precedes resolution of imaging abnormalities and more closely reflects the clinical improvement of dogs.AnimalsSeventeen dogs with AP.MethodsProspective observational study. Clinical examination, CXR, LUS, and CRP measurements performed at admission (n = 17), 2 weeks (n = 13), and 1 month after diagnosis (n = 6). All dogs received antimicrobial therapy. Lung ultrasound and CXR canine aspiration scoring systems used to compare abnormalities.ResultsB‐lines and shred signs with or without bronchograms were identified on LUS in 14 of 17 and 16 of 17, at admission. Chest radiographs and LUS scores differed significantly using both canine AP scoring systems at each time point (18 regions per dog, P < .001). Clinical and CRP normalization occurred in all dogs during follow up. Shred signs disappeared on LUS in all but 1 of 6 dogs at 1 month follow‐up, while B‐lines and CXR abnormalities persisted in 4 of 6 and all dogs, respectively.Conclusion and Clinical ImportanceLung ultrasound findings resemble those of humans with comAP and differ from CXR findings. Shred signs and high CRP concentrations better reflect clinical findings during serial evaluation of dogs.     

Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Background

Thyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease.

Hypothesis/Objectives

To investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors.

Animals

74 dogs with thyroid neoplasia.

Methods

Immunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase‐2 (cox‐2), and P‐glycoprotein (P‐gp).

Results

Fifty‐four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76–100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox‐2. Seven percent of FTCs and 70% of MTCs expressed P‐gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox‐2 (P = .013), and P‐gp (P < .001) was significantly higher in MTCs compared to FTCs.

Conclusions and Clinical Importance

VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox‐2 and P‐gp may be useful molecular targets in canine MTC.     

Breed Differences in Natriuretic Peptides in Healthy Dogs

Background

Measurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor.

Objective

To investigate breed variation in plasma concentrations of pro‐atrial natriuretic peptide 31‐67 (proANP 31‐67) and N‐terminal B‐type natriuretic peptide (NT‐proBNP) in healthy dogs.

Animals

535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project.

Methods

Absence of cardiovascular disease or other clinically relevant organ‐related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31‐67 and NT‐proBNP were measured by commercially available ELISA assays.

Results

Overall significant breed differences were found in proANP 31‐67 (P < .0001) and NT‐proBNP (P < .0001) concentrations. Pair‐wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31‐67 as well as NT‐proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT‐proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT‐proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31‐67 concentrations, twice the median concentration in Doberman Pinschers.

Conclusions and Clinical Importance

Considerable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT‐proBNP. Additional studies are needed to establish breed‐specific reference ranges.     

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats

BackgroundNephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored.ObjectivesIdentify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all‐cause mortality.AnimalsFifty‐one euthyroid client‐owned cats with International Renal Interest Society (IRIS) stages 2‐3 azotemic CKD.MethodsRetrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner‐reported time‐averaged phosphate‐restricted diet (PRD) intake, where PRD comprised ≥50%, 10‐50%, or none of food intake.ResultsNephrocalcinosis was rated as mild‐to‐severe in 78.4% and absent‐to‐minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%‐50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent‐to‐minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1‐year period, and had shorter median survival times than cats with mild‐to‐severe nephrocalcinosis.Conclusion and Clinical ImportanceHigher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats.     

Serum Biomarkers of Clinical and Cytologic Response in Dogs with Idiopathic Immune‐Mediated Polyarthropathy

Background

Immune‐mediated polyarthopathy (IMPA) is common in dogs, and is monitored by serial arthrocenteses.

Hypothesis/Objectives

Plasma C‐reactive protein (CRP), interleukin‐6 (IL‐6), and CXCL8 (interleukin‐8) would serve as noninvasive markers of joint inflammation in IMPA.

Animals

Nine client‐owned dogs with idiopathic IMPA; 6 healthy controls.

Methods

Prospective study. Plasma CRP, IL‐6, and CXCL8 were measured by ELISA at baseline, 2, and 4 weeks during treatment with prednisone at 50 mg/m²/day. Arthrocenteses, the canine brief pain inventory (CBPI), and accelerometry collars were used to assess joint inflammation, lameness, and mobility at all 3 time points.

Results

C‐reactive protein concentrations were higher in IMPA dogs (median 91.1 μg/mL, range 76.7–195.0) compared with controls (median <6.3 μg/mL, <6.3–13.7; P = .0035), and were significantly lower at week 2 (10.6 μg/mL, <6.3–48.8) and week 4 (<6.3 μg/mL, <6.3–24.4; P < .001).C‐reactive protein was correlated with median CBPI scores (r = 0.68; P = .0004), joint cellularity (r = 0.49, P = .011), and mobility by accelerometry (r = −0.42, P = .048). Plasma IL‐6 concentrations were also higher in IMPA dogs (median 45.9 pg/mL), compared with controls (median <15.7 pg/mL; P = .0008). IL‐6 was lower in IMPA dogs by week 4 (<15.7 pg/mL; P = .0099), and was modestly correlated with CBPI scores (r = 0.47, P = .023). CXCL8 did not differ significantly between IMPA and healthy dogs.

Conclusions

Plasma CRP and IL‐6 might be useful surrogate markers of synovial inflammation and disease activity in dogs with IMPA.     

Upregulation of the PI3K/Akt Pathway in the Tumorigenesis of Canine Thyroid Carcinoma

Background

Information on the genetic events leading to thyroid cancer in dogs is lacking.

Hypothesis/Objectives

Upregulation of the PI3K/Akt pathway has an important role in the tumorigenesis of thyroid carcinoma in dogs.

Animals

Fifty‐nine dogs with thyroid carcinoma and 10 healthy controls.

Methods

Quantitative RT‐PCR was performed for VEGFR‐1, VEGFR‐2, EGFR, PIK3CA, PIK3CB, PDPK1, PTEN, AKT1, AKT2, COX‐2, and CALCA. Mutation analysis was performed for known hotspots of RAS (N, K, H), PIK3CA, BRAF, RET, and for the entire coding region of PTEN.

Results

Forty‐three dogs (73%) had follicular cell thyroid carcinoma (FTC) and 16 dogs (27%) had medullary thyroid carcinoma (MTC). The relative mRNA expressions of VEGFR‐1 (P < .001), VEGFR‐2 (P = .002), PDPK1 (P < .001), AKT1 (P = .009), and AKT2 (P < .001) were increased in FTC, and those of EGFR (P < .001), VEGFR‐1 (P = .036), and PIK3CA (P = .019) were increased in MTC when compared to normal thyroid glands. Mutation analysis of K‐RAS identified 2 activating missense mutations, which also have been described in thyroid cancer of humans. A G12R substitution was present in 1 FTC and an E63K substitution was present in 1 MTC. No functional mutations were found in the sequenced regions of H‐RAS, N‐RAS, PIK3CA, BRAF, RET, and PTEN.

Conclusions and Clinical Importance

The increased expression of several genes associated with PI3K/Akt signaling suggests the involvement of this pathway in the pathogenesis of thyroid carcinoma in dogs, warranting further research on pathway activation and gene amplification. The mutations most frequently associated with thyroid cancer in humans are rare in dogs.     

Phenotypic Characterization of Canine Intestinal Intraepithelial Lymphocytes in Dogs with Inflammatory Bowel Disease

Background

Many dogs suffering from inflammatory bowel disease (IBD) are presented to veterinary clinics. These patients are diagnosed based on a history of chronic gastrointestinal signs and biopsy‐confirmed histopathologic intestinal inflammation. Intestinal intraepithelial lymphocytes (IEL) are part of the first line of defense in the gastrointestinal immune system. Alterations in IEL subsets may play a role in the pathogenesis of IBD.

Hypothesis

The aim of this study was to characterize the phenotypes of IEL in dogs with IBD compared with healthy control dogs.

Animals

Intestinal intraepithelial lymphocytes subpopulations of control dogs (n = 5) obtained from endoscopic biopsies (EB) were compared to those obtained from full thickness biopsies (FTB) on the same day. In addition, the phenotypes of IEL from FTB of control dogs (n = 10) were compared with EB of IBD dogs (n = 10). Each participant was scored clinically using the canine inflammatory bowel disease activity index (CIBDAI), and all samples were graded histopathologically. Three‐color flow cytometry of isolated IEL was performed using monoclonal antibodies against T‐ and B‐lymphocyte subpopulations.

Results

No significant differences in the composition of IEL subpopulations were found in control dogs based on method of biopsy. The IBD dogs had significantly higher CIBDAI and histopathologic scores compared with control dogs and their IEL contained a significantly higher frequency TCRγδ T‐cells.

Conclusions and Clinical Importance

Endoscopic biopsies provide suitable samples for 3‐color flow cytometry when studying canine intestinal IEL and IBD patients show significant changes of major T‐cell subsets compared to healthy control dogs.     

Dobutamine Stress Echocardiography for Assessment of Systolic Function in Dogs with Experimentally Induced Mitral Regurgitation

Background

Systolic dysfunction is associated with poor outcomes in dogs with myxomatous mitral valve disease. However, assessment of systolic variables by conventional echocardiographic methods is difficult in these dogs because of mitral regurgitation (MR).

Hypothesis

We hypothesized that assessment of systolic function by dobutamine stress may identify systolic dysfunction in dogs with MR, and that 2‐dimensional speckle‐tracking echocardiography (2D‐STE) could quantitatively evaluate myocardial function.

Animals

Anesthetized dogs with experimentally induced MR.

Methods

Dogs were examined for systolic myocardial deformations using 2D‐STE during dobutamine infusion before and 3 and 6 months after MR induction. We evaluated peak systolic rotation and rotation rate in each basal and apical view; peak systolic torsion and torsion rate were also calculated.

Results

Invasive peak positive first derivatives of left ventricular pressure (dp/dt) were significantly decreased in dogs 6 months after induction of MR compared with pre‐MR results. After 3 and 6 months of MR, dogs had diminished peak systolic torsion values and torsion rates in response to dobutamine infusion compared with pre‐MR results (3 months, P < .001 and P = .006; 6 months, P = .003 and P = .021). These results were significantly correlated with overall invasive dp/dt (r = 0.644, P < .001; r = 0.696, P < .001).

Conclusions and Clinical Importance

Decreased torsion during dobutamine infusion in dogs with MR may reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be useful for the assessment of systolic function in dogs with MR.     

Short‐ and Long‐Term Cure Rates of Short‐Duration Trimethoprim‐Sulfamethoxazole Treatment in Female Dogs with Uncomplicated Bacterial Cystitis

Background

Long‐duration beta‐lactam antibiotics are used for empirical treatment in female dogs with uncomplicated bacterial cystitis. However, women with bacterial cystitis are treated with short‐duration potentiated sulfonamides because longer courses of beta‐lactams result in lower cure and higher recurrence rates.

Hypothesis/Objectives

Short‐duration potentiated sulfonamide treatment is more efficacious than long‐duration beta‐lactam treatment in achieving clinical and microbiological cures in female dogs with uncomplicated bacterial cystitis.

Animals

Thirty‐eight client‐owned female dogs.

Methods

Randomized, double‐blinded, placebo‐controlled clinical trial. Dogs were treated with TMP‐SMX (15 mg/kg PO q12h for 3 days followed by a placebo capsule PO q12h for 7 days; Group SDS; n = 20) or cephalexin (20 mg/kg PO q12h for 10 days; Group LDBL; n = 18). Dogs were monitored for clinical and microbiological cure during treatment and at short‐ and long‐term follow‐up.

Results

No statistically significant differences were found between treatment groups in clinical cure rates after 3 days of treatment (89% SDS, 94% LDBL; P = 1.00) and 4 days (85% SDS, 72% LDBL; P = .44) or >30 days (50% SDS, 65% LDBL; P = .50) after conclusion of treatment or in microbiological cure rates 4 days (59% SDS, 36% LDBL; P = .44) or >30 days (44% SDS, 20% LDBL; P = .40) after conclusion of treatment.

Conclusions and Clinical Importance

We did not identify a difference in cure rates between short‐duration sulfonamide and long‐duration beta‐lactam treatments in female dogs with uncomplicated cystitis. Long‐term cure rates in both treatment groups were low. In some female dogs, “uncomplicated” bacterial cystitis may be more complicated than previously recognized.     

Plasma and Urine Neutrophil Gelatinase–Associated Lipocalin (NGAL) in Dogs with Acute Kidney Injury or Chronic Kidney Disease

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is a protein that is used in human medicine as a real‐time indicator of acute kidney injury (AKI).

Hypothesis

Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL‐to‐creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD).

Animals

18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI.

Methods

Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single‐injection plasma inulin clearance was performed in the healthy dogs.

Results

Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5–21.2), 22.0 ng/mL (7.7–62.3), and 48.3 ng/mL (5.7–469.0), respectively. UNCR was 2 × 10⁻⁸ (0–46), 1,424 × 10⁻⁸ (385–18,347), and 2,366 × 10⁻⁸ (36–994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027).

Conclusions and Clinical Importance

Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.     

Cyclooxygenase‐2 and 5‐Lipoxygenase in Dogs with Chronic Enteropathies

Background

Cyclooxygenase‐2 (COX‐2) is a key enzyme in the synthesis of pro‐inflammatory prostaglandins and 5‐lipoxygenase (5‐LO) is the major source of leukotrienes. Their role in IBD has been demonstrated in humans and animal models, but not in dogs with chronic enteropathies (CCE).

Hypothesis

COX‐2 and 5‐LO are upregulated in dogs with CCE.

Animals

Fifteen healthy control dogs (HCD), 10 dogs with inflammatory bowel disease (IBD), and 15 dogs with food‐responsive diarrhea (FRD).

Methods

Prospective study. mRNA expression of COX‐2, 5‐LO, IL‐1b, IL‐4, IL‐6, TNF, IL‐10 and TFG‐β was evaluated by quantitative real‐time RT‐PCR in duodenal and colonic biopsies before and after treatment.

Results

COX‐2 expression in the colon was significantly higher in IBD and FRD before and after treatment (all P < .01). IL‐1b was higher in FRD in the duodenum after treatment (P = .021). TGF‐β expression was significantly higher in the duodenum of HCD compared to FRD/IBD before treatment (both P < .001) and IBD after treatment (P = .012). There were no significant differences among groups and within groups before and after treatment for IL‐4, IL‐6, TNF, and IL‐10. There was a significant correlation between COX‐2 and IL‐1b in duodenum and colon before treatment in FRD and IBD, whereas 5‐LO correlated better with IL‐6 and TNF. IL‐10 and TGF‐β usually were correlated.

Conclusions and Clinical Importance

COX‐2 is upregulated in IBD and FRD, whereas IL‐1b and TGF‐β seem to be important pro‐ and anti‐inflammatory cytokines, respectively. The use of dual COX/5‐LO inhibitors could be an interesting alternative in the treatment of CCE.     

Prognostic Value of Left Atrial Function in Dogs with Chronic Mitral Valvular Heart Disease

Background

A strong correlation between left atrial (LA) dysfunction and the severity of cardiac disease has been described in human patients with various cardiac diseases. The role of LA dysfunction in dogs with chronic mitral valvular heart disease (CMVHD) has not been addressed.

Objectives

To investigate the correlation between LA function and the prognosis of dogs with CMVHD.

Animals

Thirty‐eight client‐owned dogs with CMVHD.

Methods

Prospective clinical cohort study. Dogs were divided into 2 groups (survivors and nonsurvivors) based on the onset of cardiac‐related death within 1 year. Physical examination and echocardiographic variables were compared between the groups. For the assessment of the comparative accuracy in identifying patients with cardiac‐related death, receiver operating characteristic (ROC) curves and multivariate logistic analysis were used.

Results

The highest accuracy was obtained for the LA active fractional area change (LA‐FAC _act), with an area under the ROC curve (AUC) of 0.95, followed by the left atrial to aortic root ratio (LA/Ao), with an AUC of 0.94; peak early diastolic mitral inflow velocity (E), with an AUC of 0.85; and LA total fractional area change (LA‐FAC _total), with an AUC of 0.85. In the multivariate logistic regression analysis, LA‐FAC _act emerged as the only independent correlate of cardiac‐related death within 1 year (odds ratio = 1.401, P = .002).

Conclusions and Clinical Importance

Regarding both the size and function, the LA has a strong correlation with the prognosis of dogs with CMVHD. The most significant independent predictor of mortality in this study was LA‐FAC _act.     

Serotonin Concentrations in Platelets,Plasma, Mitral Valve Leaflet,and Left Ventricular Myocardial Tissue in Dogs with Myxomatous Mitral Valve Disease

Hypothesis/Objectives

Altered serotonin (5‐hydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantified [5HT] in platelet‐rich plasma (PRP), platelet‐poor plasma (PPP), mitral valve leaflets (MV), and left ventricular myocardium (LV).

Animals

Forty‐five dogs comprised 4 plasma groups of Cavalier King Charles Spaniels (CKCS) or non‐CKCS, either healthy (CON) or MMVD affected: CKCS CON (n = 12); non‐CKCS CON (n = 8); CKCS MMVD (n = 14); non‐CKCS MMVD (n = 11). Twenty‐four dogs comprised 3 tissue groups: MMVD (n = 8); other‐HD (heart disease) (n = 7); non‐HD, extracardiac disease (n = 9).

Methods

High‐performance liquid chromatography measured PRP, PPP, MV, and LV [5HT].

Results

Platelet‐rich plasma platelet [5HT] was greater in CKCS CON (1.83 femtograms/platelet [fg/plt]; range, 0.20–4.76; P = .002), CKCS MMVD (1.58 fg/plt; range, 0.70–4.03; P = .005), and non‐CKCS MMVD (1.72 fg/plt; range, 0.85–4.44; P = .003) versus non‐CKCS CON (0.92 fg/plt; range, 0.63–1.30). There was no group difference in PPP [5HT]. MV [5HT] was significantly higher in MMVD (32.4 ng/mg; range, 8.4–106.7) versus non‐HD (3.6 ng/mg; range, 0–28.3; P = .01) and LV [5HT] was significantly higher in MMVD (11.9 ng/mg; range, 4.0–104.8) versus other‐HD (0.9 ng/mg; range, 0–10.1; P = .011) and non‐HD (2.5 ng/mg; range, 0–6.9; P = .001).

Conclusions and Clinical Importance

Platelet [5HT] was highest in healthy CKCS and both MMVD groups, but plasma [5HT] showed no group differences. Tissue [5HT] was highest in MV and LV of MMVD‐affected dogs, suggesting altered 5HT signaling as a potential feature of MMVD. Interactions of platelet, valvular, and myocardial 5HT signaling warrant further investigation.     

Relationship among Insulin Resistance,Growth Hormone,and Insulin‐Like Growth Factor I Concentrations in Diestrous Swedish Elkhounds

Background

In the dog, the normal estrous cycle includes a prolonged luteal phase. Progesterone stimulates local canine mammary growth hormone (GH) production, which may act systemically and contribute to insulin resistance. Swedish Elkhounds are predisposed to progesterone‐related diabetes mellitus, and the relationship among insulin resistance, GH, and insulin‐like growth factor I (IGF‐I) is of particular interest.

Objective

To study insulin resistance in relation to GH and IGF‐I in nondiabetic Swedish Elkhounds during diestrus. We also assessed whether alterations in these hormones could predict diestrus‐linked diseases and all‐cause mortality.

Animals

Eighty‐four privately owned female intact Swedish Elkhounds >4 years of age.

Methods

Blood sampling and clinical examination during luteal phase, with a follow‐up questionnaire after 20 months. Insulin resistance was calculated by homeostasis model assessment (HOMA‐IR).

Results

In multivariable regression analysis, GH was positively associated with HOMA‐IR (P = .009). An increase in GH of 1 ng/mL was associated with a 12.7% increase in HOMA‐IR. Moreover, C‐peptide was positively associated with IGF‐I (P = .04), and an increase in C‐peptide of 0.1 ng/mL was associated with a 6.9% increase in IGF‐I. Structural equation modeling supported these results. Twenty‐three animals were found to have previously unrecognized mammary masses and had higher GH (P < .0001) and IGF‐I (P = .007) than dogs without mammary masses (n = 61). There was no association between high GH and IGF‐I concentrations at sampling and future mammary masses.

Conclusion

We showed that GH was strongly associated with insulin resistance in older Swedish Elkhounds during diestrus.