Incremental predictive value of echocardiographic indices of right ventricular function in the assessment of long-term prognosis in dogs with myxomatous mitral valve disease

IntroductionFew studies have evaluated the utility of echocardiographic indices of right ventricular (RV) function in predicting prognosis in dogs with myxomatous mitral valve disease (MMVD).AnimalsSixty-seven client-owned dogs were diagnosed with MMVD.Materials and methodsclinical cohort study. Dogs diagnosed with American college of veterinary internal medicine (ACVIM) stage B2, C or D between April 2014 and March 2017 were enrolled. Long-term outcomes were assessed by telephone or from the medical record. The primary end-point was defined as cardiac-related death. Echocardiographic indices of RV function, including the RV Tei index, free wall and septal RV longitudinal strain, were obtained. Univariable and multivariable Cox proportional hazard analyses were used to identify variables predictive of cardiac-related death.ResultsTwenty-four dogs died during the follow-up period. The median follow-up time was 482 days, and the median survival time for dogs with cardiac-related death was 230 days. For cardiac-related death, peak early diastolic mitral inflow velocity, ACVIM stage C or D, tricuspid regurgitation velocity, RV Tei index and RV end-diastolic area were predictors in univariable Cox proportional hazard analysis. In multivariable Cox proportional analysis adjusted for the left atrial to aorta ratio, peak early diastolic mitral inflow velocity and ACVIM stage, an increase in the Tei index by 0.1 increased the hazard ratio of cardiac-related death by 33% (95% confidence interval, 16–70%; P = 0.002).ConclusionsIn dogs with MMVD, RV dysfunction assessed by the Tei index is an independent predictor of cardiac-related death.     

Pharmacodynamic assessment of diuretic efficacy and braking in a furosemide continuous infusion model

Introduction

Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide.

Effect of atorvastatin on oxidative stress and inflammation markers in myxomatous mitral valve disease in dogs: A comparison of subclinical and clinical stages

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disorder found in dogs. The disease process can lead to heart failure (HF) and has been found to be associated with oxidative stress and inflammation. Statins exert antioxidant and anti‐inflammatory effects in human HF patients. However, the beneficial effects of statins in MMVD dogs are still unclear. Thirty MMVD dogs were enrolled in the study and were divided into two groups: MMVD without HF dogs (n = 15) and MMVD with HF dogs (n = 15). Atorvastatin (8 mg kg^?1 day^?1) was administered orally to all dogs for 4 weeks. All dogs underwent physical examination and cardiac examination at the beginning and end of the experiment, including baseline values for hematology, blood chemistry profile, lipid profile, N‐terminal pro B‐type natriuretic peptide, oxidative stress marker (8‐isoprostane), and inflammatory marker (tumor necrosis factor alpha). The results showed that atorvastatin reduced plasma cholesterol levels in both groups. In addition, plasma concentrations of 8‐isoprostane, tumor necrosis factor alpha, and N‐terminal pro B‐type natriuretic peptide were significantly lower after atorvastatin administration, but only in MMVD dogs in the HF group. Atorvastatin found to be associated with possible antioxidant and inflammatory effects in dogs with HF secondary to MMVD. The potential benefits of statins in dogs with HF merits further investigation in larger, placebo‐controlled studies.     

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.     

Intermittent bolus injection versus continuous infusion of furosemide in normal adult greyhound dogs

Several studies in human subjects have demonstrated greater diuresis with constant rate infusion (CRI) furosemide than intermittent bolus (IB) furosemide. This study was conducted to compare the diuretic efficacy of the same total dose of IB furosemide and CRI furosemide in 6 healthy, adult Greyhound dogs in a randomized crossover design with a 2-week washout period between treatments. For IB administration, dogs received 3 mg/kg at 0 and 4 hours. For CRI administration, dogs received a 0.66 mg/kg loading dose followed by 0.66 mg/kg/h over 8 hours. The same volume of fluid was administered for both methods. Urine output was quantified hourly. Urine electrolyte concentrations, urine specific gravity (USG), packed cell volume (PCV), total protein (TP), serum electrolyte concentrations, total carbon dioxide (TCO2), serum creatinine (sCr), and blood urea nitrogen (BUN) were determined every 2 hours. Urine production and water intake were greater (P < or = 0.05) for CRI than IB. Urine sodium and calcium losses were greater (P < 0.05) and urine potassium loss was less (P = 0.03) for CRI than IB, but there was no evidence of a difference between methods for urine magnesium and chloride losses. Serum chloride concentration was less (P < 0.001), sCr concentration greater (P = 0.04). TP greater (P = 0.01), and PCV greater (P = 0.003) for CRI than IB. No differences in USG, TCO2, BUN, or serum potassium, sodium, and magnesium concentrations were detected between methods. The same total dose of CRI furosemide resulted in more diuresis, natriuresis, and calciuresis and less kaliuresis than IB furosemide in these normal Greyhound dogs over 8 hours, suggesting that furosemide is a more effective diuretic when administered by CRI than by IB.     

The pharmacokinetics and pharmacodynamics of furosemide in anesthetized dogs with normal and experimentally decreased renal function

The pharmacokinetics and the biliary and urinary excretions following intravenous administration of furosemide (5 mg/kg) were investigated in the anesthetized dogs with normal and experimentally reduced renal function. After the administration, furosemide caused diuretic and choleretic response, and was excreted into urine and bile at almost similar rate to plasma concentration decay in normal dogs. Half maximum diuretic response was obtained at 1.5 micrograms/ml of plasma concentration and 100 micrograms/min of urinary excretion rate of furosemide. Acute renal failure was produced in dogs by the intravenous administration of mercuric chloride (HgCl2, 2 mg/kg). In HgCl2-treated dogs, the prolongation of half life (T1/2 beta) and the decrease in plasma clearance were noted with the decreased diuretic response. These changes in parameters appeared to be associated with the decrease in excretion of furosemide into the urine, but not into the bile. Plasma level-diuretic response relationship was extensively shifted to the right in HgCl2-treated dogs, while urinary dose-response relationship did not change significantly between two groups. These results suggest that the decreased response to furosemide in HgCl2-treated dogs seems to be due to the decreased renal clearance rather than to the subsensitivity to furosemide on the site of action.     

Caudal vena cava point-of-care ultrasound in dogs with degenerative mitral valve disease without clinically important right heart disease

ObjectivesCaudal vena cava (CVC) diameter and collapsibility index (CVC_D and CVC_CI) have been used to assess intravascular volume status (IVS). Maladaptations with progressive degenerative mitral valve disease (DMVD) lead to hypervolemia. We hypothesised that stages of DMVD will affect ultrasonographic CVC variables in dogs without clinically important right heart disease.Animals, materials and methodsThis retrospective study included 79 dogs with DMVD presented to the cardiology department between January 2017 and 2019. Subxiphoid views were used to obtain CVC cineloops. By visual inspection, CVC was subjectively scored as flat, normal or fat. Maximal and minimal CVC_D were measured and indexed to aortic diameter (CVC_D-max/Ao and CVC_D-min/Ao); CVC_CI was calculated as (CVC_D-max-CVC_D-min)/CVC_D-max. Fisher's exact and Kruskal–Wallis tests were used to compare CVC variables.ResultsSubjective assessment was associated with American College of Veterinary Internal Medicine (ACVIM) stages (P < 0.001). The proportion of fat CVC was greater in stages C and D. In stage D, CVC_D-max/Ao was larger compared with stages B1, B2 and C (P = 0.002, P = 0.002 and P = 0.035, respectively). In stages C and D, CVC_D-min/Ao was larger compared with B1 (P = 0.016 and P = 0.001) and B2 (P = 0.002 and P < 0.001. In stages C and D, CVC_CI was less than stage B1 (P = 0.016 and P = 0.044) and B2 (P = 0.001 and P = 0.010).ConclusionsIn dogs with DMVD without clinically important right heart disease, CVC variables differ across ACVIM stage. Subjective and objective CVC variables may be used to predict hypervolemia.     

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.     

Effect of spironolactone on diuresis and urine sodium and potassium excretion in healthy dogs

ObjectivesTo document the diuretic effect of different oral doses of spironolactone (SP) in healthy dogs.BackgroundSP is currently mentioned as a diuretic agent in the dog. However, the recommended doses were empirically defined and their corresponding diuretic effect has never been documented in dogs.Animals, materials and methodsEight adult Beagle dogs were used for two separate 2 * 2 cross-over designs. In the first cross-over, 4 dogs received SP orally for 8 days at 1 and 2 mg/kg per day. In the second cross-over the 4 other dogs received SP similarly, but at 4 and 8 mg/kg per day. Dogs were weighed on the first and last day of each period. Plasma SP and canrenone (the main active metabolite of SP) were assayed by high performance liquid chromatography (HPLC). Daily water consumption, urine weight, urine specific gravity, and urine excretion of sodium and potassium were measured during the SP treatment.ResultsTwo hours after SP administration, SP was metabolized into canrenone. A significant 14 and 22% decrease in urine potassium excretion was observed at 1 and 2 mg/kg, respectively, but not at the two other dose levels. Daily water consumption, urine weight, urine specific gravity, and urine excretion of sodium were not significantly altered by the SP treatment regardless of dose.ConclusionsRepeated oral administration of SP at 1, 2, 4 or 8 mg/kg for 8 days had no effect on water and sodium diuresis in healthy 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.     

Retrospective evaluation of notched and fragmented QRS complex in dogs with naturally occurring myxomatous mitral valve disease

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. The association of QRS notching (nQRS) or fragmentation (fQRS) with disease severity is currently unknown. The study objective was to assess the prevalence of nQRS and fQRS in dogs with MMVD and its severity according to ACVIM classification and to compare the results with a group of healthy dogs. This retrospective cross-sectional study included 34 healthy control dogs and 155 dogs with spontaneous MMVD (42% of dogs in class B1, 23% in class B2 and 35% in class C). fQRS was defined as nQRS complexes in two contiguous leads in the frontal plane (leads I and aVL) and (II, III or aVF). A one-way ANOVA with Bonferroni post-hoc test was used to assess the differences in continuous data between control and MMVD groups. Of the MMVD group, 58% showed nQRS in at least one lead and 27% presented fQRS. There was no difference between the number of leads with a nQRS and disease severity (p = 0.75) nor did the number of leads with a nQRS correlate with left atrial size (r = 0.48; p = 0.5). The number of dogs with fQRS did not differ among classes of MMVD (p = 0.21). nQRS and fQRS were more prevalent in dogs with MMVD compared to control dogs (p < 0.01). This study did not identify any relationship between the number of leads with a nQRS and disease severity. However, dogs with MMVD had a higher prevalence of nQRS and fQRS compared to control group.     

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 Chronic Furosemide on Salt and Water Intake of Ponies

Furosemide is used acutely in racehorses and chronically for treatment of edema and congestive heart failure, but the behavioral effects on horses of chronic administration of this drug have not been studied. The objectives of this study were to measure salt and water intake as well as sodium and water losses in ponies treated chronically with furosemide. The salt and water intake of ponies was measured daily for 3 weeks before and 3 weeks during treatment with furosemide at a dose of 0.5 mg/kg/d. Fecal dry matter was measured for 9 days before and during furosemide treatment by collecting a fecal sample from each pony's stall and drying it overnight in a 100°C oven. Urine volume and urine sodium content were measured daily for three consecutive days during pretreatment, treatment, and post-treatment periods so that sodium and water status could be calculated. Sodium chloride intake increased in ponies treated daily with furosemide from 7.9 ± 2.2 (standard error of the mean) to 20.3 ± 2.4 g/d and was significantly higher than control for all weeks of treatment (P < .03). Water intake was also significantly increased from 8.9 ± 1 during the control period to 11 ± 0.7 kg/d during furosemide treatment (P < .001), and the ponies drank more water than they lost. Urine volume and urine sodium concentrations increased significantly during treatment with the diuretic, whereas urinary potassium and calcium concentrations decreased.     

Two-dimensional echocardiographic estimates of left atrial function in healthy dogs and dogs with myxomatous mitral valve disease

Objectives

To provide reference intervals for 2-dimensional linear and area-based estimates of left atrial (LA) function in healthy dogs and to evaluate the ability of estimates of LA function to differentiate dogs with subclinical myxomatous mitral valve disease (MMVD) and similarly affected dogs with congestive heart failure (CHF).

Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure

IntroductionDilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy.HypothesisPrior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF).Animals and methodsA retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan–Meier curves and the Cox proportional-hazards model.ResultsThe median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs.ConclusionsPrior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.     

Anatomic regurgitant orifice area obtained using 3D-echocardiography as an indicator of severity of mitral regurgitation in dogs with myxomatous mitral valve disease

Objectives

To determine feasibility and repeatability of measuring the anatomic regurgitant orifice area (AROA) using real-time three-dimensional transthoracic echocardiography (RT3DE) in dogs with myxomatous mitral valve disease (MMVD), and to investigate differences in the AROA of dogs with different disease severity and in different American College of Veterinary Internal Medicine (ACVIM) stages.

Effect of torsemide and furosemide on clinical,laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease

ObjectivesDiuretic therapy reduces preload and relieves congestion secondary to cardiac dysfunction. Torsemide (torasemide) is a loop diuretic with longer duration of action, decreased susceptibility to diuretic resistance, and adjunctive aldosterone antagonist properties compared with furosemide. We hypothesized that torsemide would be well tolerated and no less effective than furosemide at diuresis, control of clinical signs, and maintenance of quality of life (QOL) in dogs with congestive heart failure (CHF).Animals, materials and methodsSeven client-owned dogs with stable CHF receiving twice daily oral furosemide and adjunctive medications. Utilizing a double-blinded, randomized, crossover design, dogs were administered either oral furosemide at their current dose or an equivalent oral dose of torsemide (1/10 of the daily furosemide dose divided into twice daily dosing) on day 0. Crossover occurred at day 7 and the study ended on day 14. Clinical, laboratory, radiographic, and QOL variables were evaluated on days 0, 7 and 14.ResultsNo dogs developed recurrent CHF during the study. Mean furosemide dose on day 0 was 5.13 mg/kg/day (range 2.8–9.6). Following torsemide treatment, creatinine (P = 0.020), urea nitrogen (P = 0.013), phosphorus (P = 0.032), albumin (P = 0.019), carbon dioxide (P = 0.015) and anion gap (P = 0.005) were significantly increased, and urine specific gravity (P = 0.004) and chloride (P = 0.021) were significantly decreased compared with furosemide dosing. No differences in QOL were found.ConclusionsResults indicate that torsemide is equivalent to furosemide at controlling clinical signs of CHF in dogs and is likely to achieve greater diuresis vs. furosemide. Larger clinical trials evaluating torsemide as a first or second-line loop diuretic for congestive heart failure in dogs are warranted.     

Change of Vertebral Left Atrial Size in Dogs With Preclinical Myxomatous Mitral Valve Disease Prior to the Onset of Congestive Heart Failure

Introduction/objectivesIt has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility.Animals, materials and methodsForty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared.ResultsAt the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83–155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not.ConclusionsVLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.     

Effects of oral administration of furosemide and torsemide in healthy dogs

OBJECTIVE: To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance. RESULTS: Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.