Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Background

Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.

Hypothesis/Objectives

The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse‐administered toceranib phosphate (TOC) combined with lomustine.

Animals

Forty‐seven client‐owned dogs with measurable MCT.

Methods

Toceranib phosphate was given PO on days 1, 3 and 5 of a 21‐day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m². All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.

Results

The MTD of lomustine was established at 50 mg/m² when combined with pulse‐administered TOC; the dose‐limiting toxicity was neutropenia. Forty‐one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression‐free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.

Conclusions and clinical importance

Combined treatment with pulse‐administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.     

Serial Evaluation of Abdominal Fluid and Serum Amino‐terminal pro‐C‐type Natriuretic Peptide in Dogs with Septic Peritonitis

Background

Serum N‐terminal pro‐C‐natriuretic peptide (NT‐proCNP) has shown promise as a diagnostic biomarker for sepsis. Its sensitivity to detect dogs with septic peritonitis (SP) is reportedly low, perhaps attributable to the compartmentalization of NT‐proCNP in the abdominal cavity.

Objectives

To evaluate the use of an ELISA for the measurement of NT‐proCNP in canine abdominal fluid and to describe the peri‐operative pattern of abdominal fluid and serum NT‐proCNP concentrations in dogs with SP.

Animals

Five client‐owned dogs with nonseptic abdominal effusion of varying etiologies and 12 client‐owned dogs with SP undergoing abdominal surgery and placement of a closed‐suction abdominal drain (CSAD). Six dogs were included upon hospital admission; 6 were included the day after surgery.

Methods

Prospective pilot study. A commercially available ELISA kit was analytically validated for use on canine abdominal fluid. The NT‐proCNP concentrations were measured in the abdominal fluid of control dogs, and in serum and abdominal fluid of dogs with SP from admission for CSAD removal.

Results

In dogs with SP, admission abdominal fluid NT‐proCNP concentrations were lower than the concurrent serum concentrations (P = 0.031), and lower than control canine abdominal fluid concentrations (P = 0.015). Postoperatively, abdominal fluid NT‐proCNP concentrations remained lower than serum concentrations (P < 0.050), except on day 4.

Conclusions and Clinical Importance

The ELISA kit was able to measure NT‐proCNP in canine abdominal fluid. In dogs with SP, low serum NT‐proCNP concentrations cannot be explained by abdominal compartmentalization.     

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.     

Plasma Vitamin D Metabolites and C‐Reactive Protein in Stage‐Stop Racing Endurance Sled Dogs

Background

Dogs are a unique model for examining the effects of exercise on vitamin D status because of their lack of vitamin D synthesis by UV exposure. In addition, the inflammatory response may be associated with hypovitaminosis D.

Objectives

To investigate the effects of several days of endurance exercise on plasma vitamin D (25‐(OH)D₃, 24,25‐(OH)D₃ and 1,25(OH)D₃) and serum C‐reactive protein (CRP) concentrations in stage‐stop racing sled dogs.

Animals

12 racing sled dogs and 8 control dogs.

Methods

Blood was collected before the race and immediately after racing on days 2 and 8. Plasma vitamin D metabolites and serum CRP concentrations were measured.

Results

Racing dogs showed a significant increase in 25(OH)D₃ on day 2 (P = .027) and day 8 of the race (P < .001), whereas no increases were observed in control dogs. The plasma concentration of 24,25(OH)D₃ showed a significant increase by day 8 (P < .001). There were no significant changes in 1,25(OH) D₃ concentrations across all time points and groups. Racing dogs had significantly increased CRP concentrations by day 2 (39.3 ± 30.1 μg/mL; P < .001).

Conclusions and Clinical Importance

Increases in vitamin D metabolites as well as increases in CRP concentrations were observed in racing sled dogs. This finding was contrary to the hypothesis that decreases in vitamin D status in athletes may be related to the acute phase inflammatory response during exercise. In addition, the increased 24,25(OH)D₃ concentrations compared to what is observed in other species suggests metabolic variations in dogs that lead to enhanced disposal of vitamin D.     

Incidence,Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

Background

The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and Objectives

To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals

Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods

Retrospective medical record review, from January 2009 through December 2013.

Results

Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016).

Conclusions and Clinical Importance

These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.     

The Clinical and Serological Effect of a Gluten‐Free Diet in Border Terriers with Epileptoid Cramping Syndrome

Background

Canine epileptoid cramping syndrome (CECS) is a paroxysmal movement disorder of Border Terriers (BTs). These dogs might respond to a gluten‐free diet.

Objectives

The objective of this study was to examine the clinical and serological effect of a gluten‐free diet in BTs with CECS.

Animals

Six client‐owned BTs with clinically confirmed CECS.

Methods

Dogs were prospectively recruited that had at least a 6‐month history of CECS based on the observed phenomenology (using video) and had exhibited at least 2 separate episodes on different days. Dogs were tested for anti‐transglutaminase 2 (TG2 IgA) and anti‐gliadin (AGA IgG) antibodies in the serum at presentation, and 3, 6, and 9 months after the introduction of a gluten‐free diet. Duodenal biopsies were performed in 1 dog.

Results

Serum TG2 IgA titers were increased in 6/6 BTs (P = .006) and AGA IgG titers were increased in 5/6 BTs at presentation compared to those of controls (P = .018). After 9 months, there was clinical and serological improvement in all BTs with CECS strictly adhering to a gluten‐free diet (5/5). One dog had persistently increased antibody titers. This dog scavenged horse manure. On the strict introduction of a gluten‐free diet this dog also had an improved clinical and serological response. The diet‐associated improvement was reversible in 2 dogs on completion of the study, both of which suffered a relapse of CECS on the re‐introduction of gluten.

Conclusions

Canine epileptoid cramping syndrome in BTs is a gluten‐sensitive movement disorder triggered and perpetuated by gluten and thus responsive to a gluten‐free diet.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Randomized Phase III Trial of Piroxicam in Combination with Mitoxantrone or Carboplatin for First‐Line Treatment of Urogenital Tract Transitional Cell Carcinoma in Dogs

Background

Reported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response.

Hypothesis/Objectives

To determine if the progression‐free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin.

Animals

Fifty dogs with TCC without azotemia.

Methods

Prospective open‐label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6‐week intervals. Twenty‐four dogs received carboplatin and 26 received mitoxantrone.

Results

Response was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47–1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005).

Conclusions and Clinical Importance

This study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam.     

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

Background

Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long‐term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult‐onset epilepsies.

Hypothesis/Objectives

The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood.

Animals

A total of 25 LR with a history of BFJE and 91 control dogs of the same breed.

Methods

Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog''s activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case–control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy.

Results

Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood.

Conclusions and Clinical Importance

Although the long‐term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.     

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

Background

There are no clear treatment guidelines for dogs with clinically well‐regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3–6 hours after trilostane administration are < 2.0 μg/dL.

Objective

To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3–6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9–12 hours after trilostane administration, in a specific population of dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 <2 μg/dL.

Animals

Thirteen client‐owned dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 μg/dL 3–6 hours after trilostane administration.

Methods

Prospective study. Dogs had a second ACTH stimulation test performed 9–12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t‐test.

Results

Cortisol concentrations before (1.4 ± 0.3 μg/dL) and after the first stimulation (1.5 ± 0.3 μg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 μg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 μg/dL, P = .0001).

Conclusions and clinical importance

In dogs with clinically well‐regulated, trilostane‐treated, hyperadrenocorticism, and cortisol concentrations <2 μg/dL before and after the first stimulation, a second ACTH stimulation test performed 9–12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.     

Vitamin D Status in Different Stages of Disease Severity in Dogs with Chronic Valvular Heart Disease

Background

In humans with heart disease, vitamin D deficiency is associated with disease progression and a poor prognosis. A recent study showed that serum 25‐hydroxyvitamin D [25(OH)D] concentration, the hallmark of vitamin D status, was lower in dogs with heart failure than in normal dogs, and a low concentration was associated with poor outcome in dogs with heart failure.

Objectives

To elucidate the vitamin D status of dogs with chronic valvular heart disease (CVHD) at different stages of disease severity.

Animals

Forty‐three client‐owned dogs with CVHD.

Methods

In this cross‐sectional study, dogs were divided into 3 groups (14 dogs in Stage B1, 17 dogs in Stage B2, and 12 dogs in Stage C/D) according to ACVIM guidelines. Dogs underwent clinical examination including echocardiography. Serum 25(OH)D concentrations were measured in each dog.

Results

Serum 25(OH)D concentration was significantly lower in Stage B2 (median, 33.2 nmol/L; range, 4.9–171.7 nmol/L) and C/D (13.1 nmol/L; 4.9–58.1 nmol/L) than in Stage B1 (52.5 nmol/L; 33.5–178.0 nmol/L) and was not significantly different between Stage B2 and Stage C/D. Among clinical variables, there were significant negative correlations between 25(OH)D concentration and both left atrial‐to‐aortic root ratio and left ventricular end‐diastolic diameter normalized for body weight.

Conclusions and Clinical Importance

These results indicate that vitamin D status is associated with the degree of cardiac remodeling, and the serum 25(OH)D concentration begins to decrease before the onset of heart failure in dogs with CVHD.     

Cognitive Function,Progression of Age‐related Behavioral Changes,Biomarkers, and Survival in Dogs More Than 8 Years Old

Background

Canine cognitive dysfunction (CCD) is an age‐dependent neurodegenerative condition dominated by changes in behavioral patterns. Cohort studies investigating cognitive status in dogs are lacking.

Objectives

To investigate cognitive function, progression of age‐related behavioral changes, survival, and possible biomarkers of CCD in aged dogs.

Animals

Fifty‐one dogs >8 years old; 21 with no cognitive deficits, 17 with mild cognitive impairments (MCI) and 13 with CCD.

Methods

Longitudinal study. Recruitment period of 12 months and an observational period of 24 months including a baseline and 3 planned subsequent assessments. Cognitive status was determined using validated questionnaires. Plasma Aβ‐peptides were quantified using commercial ELISA assays and cytokines by a validated immunoassay.

Results

Signs characterizing dogs with CCD were aimless wandering, staring into space, avoid getting patted, difficulty finding dropped food and anxiety. Thirty‐three percent of dogs with a normal cognitive status progressed to MCI and 22% classified as MCI progressed to CCD during the study period. For 6 dogs diagnosed with CCD, signs of cognitive dysfunction increased with time. A diagnosis of CCD did not affect survival. The level of plasma Aβ₄₂ was significantly increased (P < .05) in the CCD group (92.8 ± 24.0 pg/mL) compared to the MCI (77.0 ± 12.3 pg/mL) and normal group (74.9 ± 10.0 pg/mL), but no significant differences in concentrations of systemic inflammatory markers were detected.

Conclusions

Canine cognitive dysfunction is a progressive disorder with an individual variability in the rate of cognitive decline and clinical signs. Plasma Aβ₄₂ seems to be an interesting plasma biomarker of CCD.     

Quantitative Contrast‐enhanced Ultrasonographic Assessment of Naturally Occurring Pancreatitis in Dogs

Background

Quantitative contrast‐enhanced ultrasonography (CEUS) can detect pancreatic perfusion changes in experimentally induced canine pancreatitis. However, its usefulness in detecting perfusion changes in naturally occurring pancreatitis is unclear.

Hypothesis/Objectives

To determine the feasibility of using CEUS to detect pancreatic and duodenal perfusion changes in naturally occurring canine pancreatitis.

Animals

Twenty‐three client‐owned dogs with pancreatitis, 12 healthy control dogs.

Methods

Dogs diagnosed with pancreatitis were prospectively included. CEUS of the pancreas and duodenum were performed. Time‐intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusion parameters were obtained for statistical analyses: time to initial up‐slope, peak time (Tp), time to wash‐out (TTW), peak intensity (PI), and area under the curve (AUC).

Results

For the pancreas, Tp of the pancreatitis group was prolonged when compared to controls (62 ± 11 seconds versus 39 ± 13 seconds; P < .001). TTW also was prolonged but not significantly (268 ± 69 seconds versus 228 ± 47 seconds; P = .47). PI and AUC were increased when compared to controls (95 ± 15 versus 78 ± 13 MPV; P = .009 and 14,900 ± 3,400 versus 11,000 ± 2,800 MPV*s; P = .013, respectively). For the duodenum, PI and AUC were significantly increased in the pancreatitis group when compared to controls.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasonography can detect pancreatic perfusion changes in naturally occurring canine pancreatitis characterized by delayed peak with prolonged hyperechoic enhancement of the pancreas on CEUS. Additionally, duodenal perfusion changes secondary to pancreatitis were observed.     

Co‐infections with Respiratory Viruses in Dogs with Bacterial Pneumonia

Background

Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis of BP in dogs is complex and the role of canine respiratory viruses has not been fully evaluated.

Objectives

The aim of this study was to investigate the occurrence of viral co‐infections in dogs with BP and to assess demographic or clinical variables as well as disease severity associated with viral co‐infections.

Animals

Twenty household dogs with BP caused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused by Bordetella bronchiseptica (BBTB).

Methods

Prospective cross‐sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well as B. bronchiseptica and Mycoplasma spp. were analyzed in respiratory samples using PCR assays.

Results

CPIV was detected in 7/20 and CRCoV in 1/20 dogs with BP. Respiratory viruses were not detected in dogs with BBTB. There were no significant differences in clinical variables between BP dogs with and without a viral co‐infection.

Conclusion and Clinical Importance

Respiratory viruses were found frequently in dogs with BP and may therefore play an important role in the etiology and pathogenesis of BP. Clinical variables and disease severity did not differ between BP dogs with and without viral co‐infection.     

Pulmonary Vein‐to‐Pulmonary Artery Ratio is an Echocardiographic Index of Congestive Heart Failure in Dogs with Degenerative Mitral Valve Disease

Background

Early recognition of left‐sided congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD) is important because it influences medical therapy, timing of follow‐up, and outcome.

Hypothesis

Pulmonary vein diameter‐to‐pulmonary artery diameter ratio (PV/PA) measured by echocardiography can predict CHF.

Animals

Ninety‐eight client‐owned dogs, 37 controls, and 61 dogs with DMVD.

Methods

Prospective clinical cohort study. History, physical examination and Doppler‐echocardiography were performed. Dogs were classified as International Small Animal Cardiac Health Council class I, II or III. Congestive heart failure was identified in a subset of 56 dogs based on radiographic findings. The PV/PA was measured in bidimensional (2D) and M‐mode by 2 investigators blinded to the radiologists’ conclusions.

Results

Interobserver coefficients of variation for PV/PA acquisition and measurement were <10%. The PV/PA in control dogs was approximately 1 and increased with class of heart failure. The presence of CHF could be best predicted by measuring PV/PA in 2D echocardiography (cut‐off, 1.7; area under the curve, 0.98; CI, 0.97–0.98; P < .001) with a sensitivity of 96% and a specificity of 91%.

Conclusion and clinical importance

The PV/PA is a simple and reproducible echocardiographic variable that increases with class of heart failure and may help discriminate dogs in CHF from asymptomatic dogs with DMVD. Additional studies are required to determine whether PV/PA might provide additional information in the integrated interpretation of Doppler‐echocardiographic indices of left ventricular filling pressures and could be used for rapid assessment of CHF in dogs in a critical care setting.     

Procoagulant Microparticles in Dogs with Immune‐Mediated Hemolytic Anemia

Background

Studies of some human prothrombotic diseases suggest that phosphatidylserine‐positive (PS+) and tissue factor‐positive (TF+) microparticles (MPs) might play a role in the pathogenesis of thrombosis or serve as biomarkers of thrombotic risk.

Hypothesis/Objectives

To determine if circulating levels of PS+MP and procoagulant activity (PCA) associated with PS+MPs and TF+ MPs are increased in dogs with IMHA.

Animals

Fifteen dogs with primary or secondary IMHA and 17 clinically healthy dogs.

Methods

Prospective case‐controlled observational study. Circulating PS+MPs were measured by flow cytometry. PCA associated with PS+MPs and TF+MPs was measured by thrombin and Factor Xa generating assays, respectively.

Results

Circulating numbers of PS+MPs were not significantly higher in dogs with IMHA [control median 251,000/μL (36,992–1,141,250/μL); IMHA median 361,990/μL (21,766–47,650,600/μL) P = .30]. However, PS+MP PCA [control median 2.2 (0.0–16.8) nM PS eq; IMHA median 8.596, (0–49.33 nM PS eq) P = .01] and TF+MP PCA [control median 0.0, (0.0–0.0 pg/mL); IMHA median 0.0; (0–22.34 pg/mL], P = .04) were increased. Intravascular hemolysis, which we showed might increase PS+ and TF+MP PCA, was evident in 3 of 5 dogs with PS+MP PCA and 2 of 4 dogs with TF+MP PCA higher than controls. Underlying disease in addition to IMHA was detected in 1 of 5 dogs with PS+PCA and 3 of 4 dogs with TF+MP PCA higher than controls.

Conclusions and Clinical Importance

TF+ and PS+MP PCA is increased in some dogs with IMHA. Further studies that determine if measuring TF+ and PS+ MP PCA can help identify dogs at risk for thrombosis are warranted.     

Efficacy of Intravenous Administration of Combined Acid Suppressants in Healthy Dogs

Background

Short‐term intravenous co‐administration of famotidine and pantoprazole is used by some veterinarians to treat gastrointestinal bleeding in critically ill dogs. However, clinical studies have not evaluated the efficacy of combination acid suppressant treatment in dogs.

Hypothesis/Objectives

To compare the effect of intravenous co‐administration of famotidine and pantoprazole to monotherapy with pantoprazole on intragastric pH in dogs. We hypothesized that single agent pantoprazole would be more effective than combination with famotidine.

Animals

Twelve healthy adult colony dogs.

Methods

Randomized, 2‐way crossover design. All dogs received placebo (0.9% saline) for 24 hours followed by 1.0 mg/kg IV q12h pantoprazole or combination treatment with famotidine and pantoprazole for 3 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 0 of treatment. Mean percentage time (MPT) that intragastric pH was ≥3 and ≥4 were compared between groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.017).

Results

The MPT ± standard deviation intragastric pH was greater than ≥3 and 4 were 79 ± 17% and 68 ± 17% for pantoprazole and 74 ± 19% and 64 ± 23% for combination treatment, respectively. There were no significant differences in MPT intragastric pH was ≥3 and 4 between groups. Pantoprazole administered alone achieved pH goals established for humans with acid‐related disorders.

Conclusions and Clinical Importance

These results suggest that short‐term combination treatment with famotidine and pantoprazole is not superior to pantoprazole alone for increasing intragastric pH in dogs.     

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.     

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.     

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH

Background

The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice.

Objectives

The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs.

Animals

Twenty‐two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC).

Methods

Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation.

Results

Peak cortisol concentrations were reached after 2–4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol‐increase above the detection‐limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours.

Conclusions and Clinical Importance

The depot formulation can be used in place of the short‐acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA‐suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.