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A 7-year-old male castrated Cavalier King Charles Spaniel was hospitalized for 12 days for treatment of severe congestive heart failure secondary to myxomatous mitral valve disease. During that time, 6 serum samples from different days were analyzed for serum biochemical and renin-angiotensin-aldosterone system components. Serum chloride concentrations (ranging from 71.6 to 103.1 mmol/L) were inversely related to angiotensin I concentrations, aldosterone concentrations, a surrogate marker of renin activity, and a surrogate marker of adrenal responsiveness to angiotensin II. In light of recent studies showing that hypochloremia is associated with advanced heart failure in dogs and is associated with poor outcomes in people, the information from the dog in this report supports exploration of RAAS dysregulation as an underlying mechanism., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Background: Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging., Hypothesis/objectives: The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all-cause death in dogs with MMVD., Animals: Eight hundred sixty-nine client-owned dogs., Methods: Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium-to-aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time-dependent receiver-operator characteristic curves quantified prognostic performance., Results: For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9-4.9]; P < .001). MRSI > 173 was predictive of all-cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4-7.5]; P < .001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C., Conclusions and Clinical Importance: MRSI was predictive of outcome (onset of CHF and all-cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Diuretics, such as furosemide, are routinely administered to dogs with congestive heart failure (CHF). Traditionally, dose and determination of efficacy primarily are based on clinical signs rather than quantitative measures of drug action. Treatment of human CHF patients increasingly is guided by quantification of urine sodium concentration (uNa) and urine volume after diuretic administration. Use of these and other measures of diuretic responsiveness is associated with decreased duration of hospitalization, complication rates, future rehospitalization, and mortality. At their core, loop diuretics act through natriuresis, and attention to body sodium (Na) stores and handling offers insight into the pathophysiology of CHF and pharmacology of diuretics beyond what is achievable from clinical signs alone. Human patients with low diuretic responsiveness or diuretic resistance are at risk for difficult or incomplete decongestion that requires diuretic intensification or other remedial strategies. Identification of the specific etiology of resistance in a patient can help tailor personalized interventions. In this review, we advance the concept of loop diuretic responsiveness by highlighting Na and natriuresis. Specifically, we review body water homeostasis and congestion in light of the increasingly recognized role of interstitial Na, propose definitions for diuretic responsiveness and resistance in veterinary subjects, review relevant findings of recent studies, explain how the particular cause of resistance can guide treatment, and identify current knowledge gaps. We believe that a quantitative approach to loop diuretic usage primarily involving natriuresis will advance our understanding and care of dogs with CHF., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Background: A recent study showed higher high-sensitivity cardiac troponin I (hs-cTnI) concentrations in healthy dogs eating grain-free (GF) compared to those eating grain-inclusive (GI) diets., Hypothesis/objectives: Healthy dogs with subclinical cardiac abnormalities eating GF diets at baseline will show improvements in cardiac biomarkers and echocardiographic variables after diet change, whereas healthy dogs eating GI diets at baseline will not improve., Animals: Twenty healthy dogs with subclinical cardiac abnormalities (12 Golden Retrievers, 5 Doberman Pinschers, 3 Miniature Schnauzers)., Methods: This prospective study included dogs with increased hs-cTnI or N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, or echocardiographic abnormalities. Mixed modeling was used to evaluate echocardiographic, hs-cTnI, and NT-proBNP differences between groups (GF or GI diet at baseline) over time (1 y after diet change)., Results: Ten GF and 10 GI dogs were evaluated. There were statistically significant time: group interactions for hs-cTnI (P = .02) and normalized left ventricular internal systolic diameter (LVIDsN; P = .02), with GF dogs showing larger decreases in these variables than GI dogs. Median (range) hs-cTnI (ng/mL) for GF dogs was 0.141 (0.012-0.224) at baseline and 0.092 (0.044-0.137) at 1 y, and for GI dogs was 0.051 (0.016-0.195) at baseline and 0.060 (0.022-0.280) at 1 y. Median LVIDsN for GF dogs was 1.01 (0.70-1.30) at baseline and 0.87 (0.79-1.24) at 1 y, and for GI dogs was 1.05 (0.84-1.21) at baseline and 1.10 (0.85-1.28) at 1 y., Conclusions and Clinical Importance: Decreased hs-cTnI and LVIDsN in GF dogs after diet change supports reversibility of these subclinical myocardial abnormalities., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Background: Recent studies have investigated dogs with presumed diet-associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed., Hypothesis/objectives: To 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., Animals: Sixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs., Methods: Echocardiography, 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)., Results: At 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 Importance: Dogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Background: Diuretic braking during furosemide continuous rate infusion (FCRI) curtails urine production., Hypothesis: Renin-angiotensin-aldosterone system (RAAS) activation mediates braking, and RAAS inhibition will increase urine production., Animals: Ten healthy purpose-bred male dogs., Methods: Dogs received placebo, benazepril, or benazepril and spironolactone PO for 3 days before a 5-hour FCRI (0.66 mg/kg/h) in a 3-way, randomized, blinded, cross-over design. Body weight (BW), serum creatinine concentration (sCr), serum electrolyte concentrations, PCV, and total protein concentration were measured before PO medications, at hours 0 and 5 of FCRI, and at hour 24. During the FCRI, water intake, urine output, urine creatinine concentration, and urine electrolyte concentrations were measured hourly. Selected RAAS components were measured before and after FCRI. Variables were compared among time points and treatments., Results: Diuretic braking and urine production were not different among treatments. Loss of BW, hemoconcentration, and decreased serum chloride concentration occurred during FCRI with incomplete recovery at hour 24 for all treatments. Although unchanged during FCRI, sCr increased and serum sodium concentration decreased at hour 24 for all treatments. Plasma aldosterone and angiotensin-II concentrations increased significantly at hour 5 for all treatments, despite suppressed angiotensin-converting enzyme activity during benazepril background treatment., Conclusions: The neurohormonal profile during FCRI supports RAAS mediation of diuretic braking in this model. Background treatment with benazepril with or without spironolactone did not mitigate braking, but was well tolerated. Delayed changes in sCr and serum sodium concentration and incomplete recovery of hydration indicators caused by furosemide hold implications for clinical patients., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Background: Associations of diet with dilated cardiomyopathy are under investigation., Objectives: That cardiac assessment would show abnormalities in healthy dogs eating grain-free (GF) diets or diets with Food and Drug Administration (FDA)-listed ingredients of concern (peas, lentils, or potatoes) as top 10 ingredients (FDA-PLP), but not in dogs eating grain-inclusive (GI) diets or diets without FDA-listed ingredients of concern (PLP) in the top 10 ingredients (NoFDA-PLP)., Animals: One hundred eighty-eight healthy Doberman Pinschers, Golden Retrievers, Miniature Schnauzers, and Whippets., Methods: This study was an observational cross-sectional study. Echocardiograms, cardiac biomarkers, and blood and plasma taurine concentrations were compared between dogs eating GF (n = 26) and GI (n = 162) diets, and between FDA-PLP (n = 39) and NoFDA-PLP (n = 149) diets, controlling for age and breed. Demographic characteristics, murmurs, genetic status, and ventricular premature complexes (VPCs) during examination were compared between dogs eating different diet types., Results: No differences in echocardiographic variables, N-terminal pro-B-type natriuretic peptide or whole blood taurine were noted between dogs eating different diet types. Dogs eating GF diets had higher median high-sensitivity cardiac troponin I (hs-cTnI) (GF 0.076 ng/mL [Interquartile range (IQR), 0.028-0.156] vs. GI 0.048 [IQR, 0.0026-0.080]; P < .001) and higher median plasma taurine (GF 125 nmol/mL [IQR, 101-148] vs GI 104 [IQR, 86-123]; P = .02) than dogs eating GI diets. Dogs eating FDA-PLP diets had higher median hs-cTnI (0.059 ng/mL [IQR, 0.028-0.122]) than dogs eating NoFDA-PLP diets (0.048 [IQR, 0.025-0.085]; P = .006). A greater proportion of dogs eating FDA-PLP diets (10%) had VPCs than dogs eating NoFDA-PLP diets (2%; P = .04)., Conclusions and Clinical Importance: Higher hs-cTnI in healthy dogs eating GF and FDA-PLP diets might indicate low-level cardiomyocyte injury., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.) more...

Background: Hypochloremia associated with congestive heart failure (CHF) in dogs is likely multifactorial. Loop diuretics cause 1:2 sodium [Na + ]:chloride [Cl t>- ] loss, whereas water retention causes a 1:1 [Na + ]:[Cl - ] dilution. Mathematical [Cl - ] correction separates these effects on [Cl - ]., Hypothesis: We hypothesized that corrected [Cl - ] (c[Cl - ]) would not differ from measured [Cl - ] (m[Cl - ]) in dogs with controlled CHF because of loop diuretics, and dogs with refractory CHF would have higher c[Cl - ] than m[Cl - ], indicating relative water excess., Animals: Seventy-one client-owned dogs with acquired heart disease, without CHF (NO-CHF), 76 with Stage C CHF and 24 with Stage D CHF., Methods: Clinicopathological data from a previous study were retrospectively analyzed. Corrected [Cl - ], m[Cl - ], and differences were compared among NO-CHF, Stage C CHF, and Stage D CHF, using the formula: c[Cl - ] = (mid-reference range [Na + ]/measured [Na + ]) × m[Cl - ]., Results: Corrected [Cl - ] and m[Cl - ] were lower in Stage D vs Stage C and NO-CHF (all P < .0001). The c[Cl - ] was higher than m[Cl - ] in Stage D (P < .0001) but not Stage C or NO-CHF. Median difference between c[Cl - ] and m[Cl - ] was higher for Stage D vs Stage C (P = .0003). No hypochloremic Stage D dogs had normal c[Cl - ], but 11/24 had [Cl - ] that was increased by >2 mmol/L., Conclusions and Clinical Importance: Serum [Cl - ] increased after mathematical correction in Stage D CHF dogs but not in Stage C and NO-CHF dogs. Although c[Cl - ] was higher than m[Cl - ] in Stage D dogs supportive of relative water excess, hypochloremia persisted, consistent with concurrent loop diuretic effects on electrolytes. Future study correlating c[Cl - ] to antidiuretic hormone concentrations is warranted., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.) more...

Background: An angiotensin-converting enzyme (ACE) gene polymorphism occurs in dogs; however, functional importance is not well studied., Hypothesis: We hypothesized that dogs with the polymorphism would show alternative renin-angiotensin aldosterone system (RAAS) pathway activation and classical RAAS pathway suppression before and after ACE-inhibitor administration, as compared to dogs without the polymorphism that would show this pattern only after ACE-inhibitor administration., Animals: Twenty-one dogs with mitral valve disease that were genotyped for the ACE gene polymorphism., Methods: This retrospective study utilized stored samples from 8 ACE gene polymorphism-negative (PN) dogs and 13 ACE gene polymorphism-positive (PP) dogs before and after enalapril administration. Equilibrium analysis was performed to evaluate serum RAAS metabolites and enzyme activities. Results were compared before and after enalapril, and between groups., Results: The classical RAAS pathway was suppressed and the alternative RAAS pathway was enhanced for both genotypes after administration of enalapril, with no differences before enalapril administration. Aldosterone breakthrough occurred in both PN (38%) and PP (54%) dogs despite angiotensin II suppression. Aldosterone was significantly higher (P = .02) in ACE gene PP dogs (median, 92.17 pM; IQR, 21.85-184.70) compared to ACE gene PN dogs (median, 15.91 pM; IQR, <15.00-33.92) after enalapril., Conclusions and Clinical Importance: The ACE gene polymorphism did not alter baseline RAAS activity. Aldosterone breatkthrough in some dogs suggests nonangiotensin mediated aldosterone production that might be negatively influenced by genotype. These results support the use of aldosterone receptor antagonists with ACE-inhibitors when RAAS inhibition is indicated for dogs, especially those positive for the ACE gene polymorphism., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.) more...

Background: Refractory congestive heart failure (CHF) and associated diuretic resistance are not well defined., Objectives: To characterize renal function, electrolyte concentrations, indices of diuretic efficacy, and renin-angiotensin-aldosterone system (RAAS) activation in dogs with naturally occurring heart disease (HD) in American College of Veterinary Internal Medicine stages B1, B2, C, and D and to determine their usefulness in defining HD stages., Animals: Group 1:149 dogs with HD stages B1, B2, C, and D. Group 2:22 dogs with HD stages C and D., Methods: Group 1: Renal parameters, serum and urine electrolyte and diuretic concentrations, and urine aldosterone concentrations were measured. Medication dosages and measured variables were compared among stages. Correlation of furosemide dosages to serum concentrations was explored. Group 2: Angiotensin-converting enzyme activity and RAAS components were measured and compared among CHF stages., Results: Serum chloride concentration was the best differentiator of HD stage. Furosemide PO dosages (≤6 mg/kg/day) were weakly correlated with serum furosemide concentrations, whereas higher dosages were not significantly correlated. Angiotensin-converting enzyme inhibitor dosage and RAAS inhibition were greater in stage D, compared to stage C dogs., Conclusions and Clinical Importance: Hypochloremia is a useful marker for stage D HD in dogs. Poor furosemide dosage correlation to serum concentration may indicate variable and poor absorption, especially at higher dosages, advanced disease, or both. A small number of stage D dogs met proposed criteria for diuretic resistance. Greater RAAS inhibition in stage D versus stage C indicates effectiveness of RAAS-suppressive treatments in this group of dogs with refractory CHF., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.) more...

Background: Torsemide use for congestive heart failure (CHF) has been reported, but prescription frequency is unknown. Commercially available tablet sizes in North America limit dosing precision, indicating a need to evaluate its strength and stability in suspension., Objectives: To determine the frequency of torsemide prescriptions and to determine a beyond use date (BUD) of a compounded suspension of torsemide for oral administration stored under 2 temperature conditions for 90 days., Animals: No animals used., Methods: Pharmacy records were retrospectively reviewed for torsemide and furosemide prescriptions from 2008 to 2015 at 2 veterinary referral centers. After preliminary strength testing, compounded torsemide suspension (5 mg/mL) for oral administration was prepared using torsemide tablets suspended in OraPlus:OraSweet 1:1, buffered to a pH of 8.3 and stored at refrigeration (2-8°C) and room temperature (20-25°C) in 2 oz amber plastic bottles. Samples were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC) on days 0, 14, 30, 60, and 90., Results: Prescriptions for torsemide increased from 2008 to 2015. Analysis of the torsemide 5 mg/mL suspension for oral administration at each time point met United States Pharmacopeia (USP) requirements for torsemide content of 90-110% of label claim. The average strength at 90 days decreased to 92 ± 3% at 2-8°C and 95 ± 2% at 20-25°C. Stability testing did not detect unknown impurities., Conclusions: Increasing torsemide use warrants availability of a validated and stable compounded formulation. Our results support the assignment of a 90-day BUD for torsemide 5 mg/mL suspension for oral administration compounded in OraPlus:Sweet 1:1 buffered to a pH of 8.3., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.) more...

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., (Copyright © 2014 by the American College of Veterinary Internal Medicine.) more...

Background: Owners' perceptions and priorities regarding quality of life (QoL) are important considerations given the unknown efficacy of many commonly administered medications, stress of hospital visits, difficulties providing home care, and personal choices including euthanasia., Objective: To describe the relative importance of quality versus quantity of life to owners of cats with heart disease., Animals: Two hundred and thirty-nine cats with heart disease., Methods: Prospective questionnaire-based clinical study. Cat owners completed a questionnaire to identify important parameters when assessing their cat's QoL, the relative importance of quality versus quantity of life, and willingness to trade survival time for QoL. Variables associated with these parameters were evaluated with multivariate analyses., Results: Appetite, owner interaction, sleep patterns, and litterbox habits were deemed important to QoL. Concern over pet suffering was significantly greater than concern over life expectancy. Ninety-three percent of owners were willing to trade survival time for good QoL; 57% of these were willing to trade up to 6 months. On multivariate analysis, the only factor significantly (P=.002) associated with willingness to trade 6 months was study site. Owner concern regarding stress of administering medications at home increased with number and frequency of medications., Conclusions and Clinical Relevance: These results indicated that QoL is more important to owners of cats with heart disease than longevity. The various priorities and concerns of cat owners should be taken into account in order to provide optimal care., (Copyright © 2010 by the American College of Veterinary Internal Medicine.) more...

Cardiac troponin I (cTnI), a myocardial polypeptide, is a highly sensitive and specific biomarker of myocardial injury in people and dogs. The structure of cTnI is highly conserved across species, and equine myocardium has high reactivity with human immunoassays. The purpose of this study was to describe cTnI concentrations in normal pastured and race-training Thoroughbred horses. Ten horses on pasture and 10 horses in race training were studied. Horses were considered normal on the basis of physical examination, training performance, electrocardiography (ECG), and echocardiography. Serum cTnI concentrations were determined with a colorimetric immunoassay. The assay has an analytical sensitivity of 0.04 ng/mL. Serum cTnI concentrations in race-training horses were not significantly different from those of pastured horses. When groups were combined, mean cTnI concentration (+/- SD) was 0.047 +/- 0.085 ng/mL. and the median was 0 (range, 0-0.35 ng/mL). The 90th percentile for both groups combined was 0.11 ng/mL. This study establishes a preliminary reference range for serum cTnI in normal Thoroughbred horses. more...

Isosorbide 5-mononitrate (5-ISMN) was evaluated in normal dogs and dogs with congestive heart failure (CHF) in a randomized, blinded, and placebo-controlled study. Equilibrium blood pool imaging was used to detect changes in regional blood volume distribution. Six normal dogs were administered placebo, 2, 3, and 4 mg/kg 5-ISMN PO on separate days with a 1-week washout period between randomized dosings. Six dogs with CHF were administered placebo or 4 mg/kg 5-ISMN on separate days with a 1-week washout period between randomized dosings. Data were collected at baseline and at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 minutes after dosing. Measured variables included indirect arterial blood pressure (BP), heart rate (HR), packed cell volume (PCV), scintigraphic count rates for normal dogs, and scintigraphic count rates for CHF dogs. Blood for plasma 5-ISMN concentration determination was collected at 60 minutes. Scintigraphic counts were corrected for decay and expressed as a percentage of the whole. No differences were detected in BP, HR, PCV, thoracic blood volume percentage (TBVP), or abdominal blood volume percentage (ABVP) between placebo and 5-ISMN in normal dogs at any dose. No differences were detected in TBVP or ABVP between placebo and 5-ISMN in dogs with CHF Plasma 5-ISMN concentration exceeded the minimum therapeutic concentration in all dogs and at all doses 60 minutes after drug administration. Equilibrium blood pool imaging failed to detect a shift in blood volume with oral 5-ISMN administration at any dose tested in normal dogs and dogs with CHF, despite adequate drug absorption. On the basis of the results of this study, 5-ISMN may not be beneficial in the treatment of dogs with CHF. more...