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Background: Furosemide, a commonly used diuretic, activates the renin-angiotensin-aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses., Hypothesis/objectives: To evaluate equilibrium analysis as a practical method for RAAS quantification in horses and describe the RAAS response to a single dose of furosemide. We hypothesize that furosemide would cause transient increase in RAAS peptides in horses., Animals: 14 healthy adult thoroughbreds from a university teaching herd., Methods: Horses received either furosemide (1 mg/kg IV) or saline IV in a crossover study design. Protease-inhibited samples were compared with equilibrium analysis samples with Deming regression analysis. Renin-angiotensin-aldosterone system hormones were evaluated at 0, 0.25, 0.5, 4, and 24 hours postadministration, via equilibrium analysis. Values were compared with a mixed effects model., Results: Correlation between protease inhibition and equilibrium analysis was high for angiotensin I peptide (AngI) and angiotensin II peptide (AngII) (r = .92 and .95, respectively). Baseline RAAS peptide concentrations were below the limit of detection except AngII (median, 7.5 [range, 3.5-14.0] pmol/L). Furosemide administration resulted in an increase in AngI (8.0 [0.5-15.5] pmol/L, P = .03), AngII (33.7 [9.6-57.9] pmol/L, P = .0008), angiotensin III peptide (AngIII) (2.9 [0.9-4.9] pmol/L, P = .0005), angiotensin IV peptide (AngIV) (2.0 [0.6-3.4] pmol/L, P = .0005), and angiotensin 1-5 peptide (Ang1-5) (5.6 [1.2-5.9] pmol/L, P = .003) at 4 hours. Differences are reported as difference in the mean (95% confidence interval [CI])., Conclusions and Clinical Importance: Furosemide produced an increase in hormones associated with both the classical and alternative RAAS pathways. Serum equilibrium analysis is practical for RAAS analysis in horses., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Effects of the renin-angiotensin-aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed., Objectives: To characterize the RAAS in untreated dogs with pCKD compared to healthy, life-stage- and sex-matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan., Animals: Dogs with pCKD (n = 36) and healthy controls (n = 20)., Methods: Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1-5, and 1-7, and aldosterone, and urinary aldosterone-to-creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models., Results: Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1-5, and 1-7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan- and enalapril-treated pCKD dogs, respectively (both P < .001). Mean (95% confidence interval) percentage change from pretreatment value in serum Ang 1-7 concentration was significantly greater in telmisartan- (753% [489%-1134%]) versus enalapril-treated (149% [69%-268%]) dogs (P < .001). Serum aldosterone decreased with treatment (P = .02 for enalapril, P < .001 for telmisartan), with no difference between groups at day 30., Conclusions and Clinical Importance: Circulating RAAS activity is higher in dogs with pCKD. Compared with enalapril, treatment with telmisartan caused significantly greater increases in the presumed beneficial peptide Ang 1-7., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The renin-angiotensin-aldosterone system (RAAS) consists of bioactive angiotensin peptides, enzymatic pathways, receptors, and the steroid hormone aldosterone. The RAAS regulates blood pressure, sodium, and electrolyte homeostasis and mediates pathologic disease processes. Within this system is an alternative arm that counterbalances the vasoconstrictive, sodium and water retentive, and pro-fibrotic and inflammatory effects of the classical arm. Improved biochemical methodologies in RAAS quantification are elucidating how this complex system changes in health and disease. Future treatments for cardiovascular and kidney disease will likely involve a more nuanced manipulation of this system rather than simple blockade., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The behavior of the comprehensive circulating renin-angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored., Hypothesis/objectives: The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD., Animals: One-hundred seventeen client-owned dogs (normal = 60; B1 = 31; B2 = 26)., Methods: Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs., Results: Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2 surr ) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2 surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4-2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P < .0001; AngII, r = .8, P = .001)., Conclusions and Clinical Importance: Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2 MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: The influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin-angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKD P ) has not been determined in dogs., Objectives: Determine whether ABT occurs in dogs with CKD P and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment., Animals: Fifty-six client-owned dogs with CKD P and 31 healthy client-owned dogs., Methods: Prospective, multicenter, open-label clinical trial. Dogs were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone-to-creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein-to-creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT)., Results: Thirty-six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2-2.2)., Conclusions and Clinical Importance: Aldosterone breakthrough was common in dogs receiving RAS inhibitors for CKD p but was not associated with proteinuria outcome., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To describe the characteristics and outcomes of transcatheter patent ductus arteriosus (PDA) occlusion after incomplete or aborted surgical ligation in dogs and cats., Animals: Twelve client-owned animals (11 dogs and one cat)., Materials and Methods: This retrospective study describes data from animals with aborted or incomplete surgical PDA ligation that subsequently underwent transcatheter closure using endovascular methods. Patient demographics, reason for incomplete or aborted surgery, complications, and method of transcatheter occlusion were recorded. Data are presented as mean ± standard deviation or median (interquartile range), where appropriate., Results: For all cases, median age at surgery was 12.2 months (4.9-15.1 months) and at catheterization was 15.4 months (8.9-21.9 months), with 79 days (29-209 days) between surgical and interventional procedures. Median weight at catheterization was 4.5 kg (2.5-12.6 kg). Reasons for failed surgical ligation included hemorrhage during ductal dissection in seven dogs, residual flow in four dogs, and inability to identify the ductus in one cat. Transcatheter closure was successfully performed using a canine duct occluder in eight dogs, transarterial coil embolization in two dogs, and transvenous coil embolization in one dog and one cat. Metallic hemoclips partially obscured angiographic findings in three cases with prior surgical hemorrhage but did not prevent transcatheter closure. In all cases, ductal flow was successfully attenuated, with no or trace residual shunting on angiography and complete occlusion the following day on echocardiography., Conclusions: When surgery is unsuccessful, either owing to hemorrhage or residual flow, transcatheter closure of PDA is feasible, even in small patients., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fortunately, the majority of dogs diagnosed with heartworm infection are asymptomatic (or have only mild symptoms such as intermittent cough) and go through adulticide therapy without complication. Complications occurring with heartworm infection and during its treatment most often directly reflect the pulmonary vascular and parenchymal injury inflicted by Dirofilaria immitis. Clinical signs may include exercise intolerance, frequent cough, hemoptysis, tachypnea, and dyspnea. Severe manifestations such as heart failure and caval syndrome may prove fatal. Acute hypersensitivity reactions after initiation of macrocyclic lactone preventive therapy in microfilaremic dogs or after melarsomine injection during adulticide therapy do occur, but are uncommon. This article reviews complications associated with heartworm infection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This prospective case series evaluated the adulticidal efficacy of topical 10 % moxidectin/2.5 % imidacloprid (M/I; Advantage Multi®, Bayer, Shawnee Mission, KS, USA) and doxycycline in dogs with naturally occurring heartworm infection (HWI). Twenty-two dogs with HWI whose owners declined melarsomine were treated with M/I at the preventive dosage twice monthly for 90 days then monthly thereafter and doxycycline (median [interquartile range; IQR] dosage 12.6 [12.0-16.1] mg/kg/day) for the first 15 days. Although strict activity restriction was not imposed, owners were asked to prevent their dogs from exercising strenuously. This protocol was referred to as the MOXY protocol. Antigen testing was performed every 30-60 days, until dogs had 'no antigen detected' (NAD). Twenty-one of the 22 dogs ultimately converted to NAD by 434 days (median [IQR]), 234 (179-303). One dog remained positive 701 days after MOXY initiation and was considered a treatment failure. All sera which converted to NAD on HW antigen testing were retested after heat-treatment. Twelve dogs had NAD on the heat-treated test on the same day as having their first NAD on the conventional test. Six of 9 dogs testing positive after heat-treatment were retested and all 6 had NAD on a heat-treated test within 2-3 months. Microfilaremia was cleared in all 8 dogs re-tested. Four dogs required treatment for cough, thought due to heartworm (HW) death, an average of 89 days after initiation of MOXY. This cough was most likely due to pneumonitis with heartworm-pulmonary thromboembolism. One dog required hospitalization for 24 -h and recovered fully with corticosteroid therapy and supportive care and 2 dogs were treated in an outpatient fashion with steroids. The MOXY protocol was tolerated and 96 % (21/22) of dogs converted to NAD, though 2 dogs required greater than 1 year to achieve this result. Nonaresenical-adulticide therapy may result in pneumonitis and heartworm-pulmonary thromboembolism at unpredictable times, potentially months after initiation of macrocyclic lactone therapy and exercise restriction should be considered when using a nonarsenical protocol. Although not currently recommended by the American Heartworm Society (AHS), non-arsenical strategies are in use and the goal of this study was to evaluate the efficacy, duration of therapy, and safety of an accelerated dosing protocol of M/I with doxycycline., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: This study retrospectively evaluated outcomes and adverse radiation effects (AREs) associated with stereotactic body radiation therapy (SBRT) for canine heart base tumors (HBTs). A secondary aim was to identify any demographic or echocardiographic factors that might determine which dogs would most benefit from SBRT., Animals: Twenty-six dogs that received SBRT for an imaging-based diagnosis of a HBT were evaluated., Methods: Twenty-three dogs were treated with three fractions of 10 Gy delivered daily or every other day. The remaining 3 dogs received variable protocols of one to five fractions. Demographic, echocardiographic, and radiographic information, AREs, and treatment responses were collected. Correlations of these data with survival time were evaluated., Results: The median overall survival time was 404 days (95% confidence interval: 239-554 days). The majority of dogs experienced a partial response (25%) or stable disease (60%) for a median duration of 333 days (95% confidence interval: 94-526 days). Three dogs had progressive disease within six months of SBRT. Radiographic pneumonitis was identified in 7 of 23 dogs, and clinical pneumonitis was identified in 4 dogs. No other AREs were noted. The rate of distant metastasis was 13%. On multivariate analysis, it was found that vena caval obstruction, supraventricular and ventricular arrhythmias, clinical signs, and enlarged locoregional lymph nodes at presentation were negatively associated with survival time., Conclusions: Stereotactic body radiation therapy was delivered with a low rate and degree of normal tissue complications. Asymptomatic dogs with confirmed, progressive growth of a HBT may most likely benefit from SBRT., Competing Interests: Conflict of interest statement The authors do not have any conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction/objectives: We hypothesized that torsemide and furosemide, at approximately equipotent dosages (similar diuresis), would have comparable effects on the circulating renin-angiotensin-aldosterone system., Animals, Materials and Methods: Six, healthy, middle-aged, male Beagles were randomized to receive torsemide (0.1 mg/kg PO q 12 h), furosemide (2.0 mg/kg PO q 12 h), or placebo for 10 days during three separate periods, separated by a 10-day washout period, in a crossover design. Blood was collected on days 1, 5, and 9 and 24-h urine collection ended on days 2, 6, and 10. After repeated measures analysis and Bonferonni correction, variables with an adjusted p<0.05 were investigated further, using Tukey's method., Results: Twenty-four-hour urine production differed significantly between the diuretics only on day 10, with torsemide causing a 38% greater diuresis than furosemide. There was, however, no significant difference in average 3-day diuresis. There were no significant differences between diuretics in the 24-h urinary excretion of sodium, chloride, or potassium, though furosemide caused less kaliuresis than torsemide. Serum renin, angiotensin II, and aldosterone and the urine aldosterone-to-creatinine ratio were significantly increased in the diuretic groups, as compared to placebo on days 5/6 and 9/10. There were no significant differences in these values between diuretics. Creatinine and blood urea nitrogen concentrations rose comparably in the diuretic groups, remaining within reference intervals in all dogs., Conclusions: At approximately equipotent dosages (20:1), torsemide and furosemide produced comparable renin-angiotensin-aldosterone system activation. Torsemide's similar potassium excretion profile to furosemide decreases support for a hypothesized mineralocorticoid-receptor blocking capability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: This report provides clinical examples of upper rate behavior in dogs with dual-chamber pacemakers, with suggestions for programming alterations to avoid detrimental upper rate behavior., Animals: Six dogs with dual-chamber pacemakers displaying upper rate behavior at upper atrial tracking rates., Methods: Medical records of dogs with dual-chamber pacemakers with evidence of upper rate behavior were reviewed retrospectively from two institutions. Two of the six dogs were followed prospectively, and 24 h Holter monitors were placed to evaluate upper rate behavior correlated to programming settings., Results: Pacemaker Wenckebach or 2:1 atrioventricular block was documented in four of six dogs, and automatic mode switch was documented in two of six dogs. Twenty-four-hour Holter monitors placed on two dogs after pacemaker optimization documented a pacemaker Wenckebach window at increased atrial rates with neither dog reaching their respective 2:1 block point throughout the recording period., Conclusions: Clinicians who implant dual-chamber pacemakers should be aware of upper rate behavior in animal species with high heart rates. Optimal programming of dual-chamber pacemakers can be achieved by selecting programmed timing intervals to limit deleterious upper rate behavior and create a more physiologic ventricular response at maximum tracking rates., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Introduction: Aldosterone breakthrough (ABT) is the condition in which angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers fail to effectively suppress the activity of the renin angiotensin aldosterone system. The objective of this study was to determine if ABT occurs in dogs with naturally occurring myxomatous mitral valve disease receiving an ACEI, using the urine aldosterone to creatinine ratio (UAldo:C) as a measure of renin angiotensin aldosterone system activation., Animals, Materials and Methods: This study includes 39 dogs with myxomatous mitral valve disease. A UAldo:C cut-off definition (derived from a normal population of healthy, adult, and client-owned dogs) was used to determine the prevalence of ABT in this population. Spearman analysis and univariate logistic regression were used to evaluate the relationship between UAldo:C and ABT (yes/no) and eight variables (age, serum K + concentration, serum creatinine concentration, ACEI therapy duration and ACEI dosage, furosemide therapy duration and furosemide dosage, and urine sample storage time). Finally, the UAldo:C in dogs receiving spironolactone, as part congestive heart failure (CHF) therapy, was compared to dogs with CHF that were not receiving spironolactone., Results: The prevalence of ABT was 32% in dogs with CHF and 30% in dogs without CHF. There was no relationship between either the UAldo:C or the likelihood of ABT and the eight variables. Therapy with spironolactone lead to a significant elevation of the UAldo:C., Discussion: Using the UAldo:C and a relatively stringent definition of ABT, it appears that incomplete RAAS blockade is common in dogs with MMVD receiving an ACEI. The prevalence of ABT in this canine population mirrors that reported in humans. While the mechanism of ABT is likely multifactorial and still poorly understood, the proven existence of ABT in dogs offers the potential to improve the prognosis for MMVD with the addition of a mineralocorticoid receptor blocker to current therapeutic regimens., Conclusions: Approximately 30% of dogs being treated for heart disease and CHF satisfied the definition of ABT. Identifying patient subpopulations experiencing ABT may help guide future study design and clinical decision-making., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to evaluate subacute changes in renin-angiotensin-aldosterone system (RAAS) activity during angiotensin-converting enzyme inhibitor (ACEI) therapy in dogs with experimental RAAS activation., Methods: Analysis of data (urine aldosterone:creatinine ratio (UAldo:C) and serum angiotensin-converting enzyme activity), in 31 healthy dogs with furosemide or amlodipine-activated RAAS that received an ACEI. When furosemide or amlodipine activation of RAAS preceded ACEI administration, incomplete RAAS blockade (IRB) was defined as a UAldo:C greater than (a) the dog's 'activated' baseline value or (b) a population-derived cut-off value (mean + 2 SD (>1.0 μg/g) of pretreatment UAldo:C from our population of research dogs). In studies where RAAS activation occurred concurrently with ACEIs, IRB was defined as (a) a UAldo:C greater than either twofold the dog's prestimulation baseline value or (b) 1.0 µg/g. Dogs were followed for 7-17 days., Results: Serum angiotensin-converting enzyme activity was measured in 19 dogs and was significantly reduced (P<0.0001) after ACEI administration. The overall incidence of IRB, when RAAS activation preceded ACEI administration, was 33% and 8% for definitions (a) and (b), respectively. The overall incidence of IRB, when ACEIs were concurrent with RAAS activation, was 65% and 61% for definitions (a) and (b), respectively., Conclusion: Increases in UAldo:C, despite ACEI administration, is evidence of IRB in this subacute model of experimental RAAS activation and suppression., (© The Author(s) 2016.)

Objective: To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS)., Animals: 6 healthy Beagles., Procedures: 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7., Results: High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C., Conclusions and Clinical Relevance: In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

Studies in our laboratory have revealed that furosemide-induced RAAS activation, evaluated via the urine aldosterone-to-creatinine ratio (UAldo:C), was not attenuated by the coadministration of benazepril, while enalapril successfully suppressed amlodipine-induced urinary aldosterone excretion. This study was designed to evaluate the efficacy of enalapril in suppressing ACE activity and furosemide-induced circulating RAAS activation. Failure to do so would suggest that this failure may be a drug class effect. We hypothesized that enalapril would suppress ACE activity and furosemide-induced circulating RAAS activation. Sixteen healthy hound dogs. The effect of furosemide (2 mg/kg PO, q12 h; Group F) and furosemide plus enalapril (0.5 mg/kg PO, q12 h; Group FE) on circulating RAAS was determined by plasma ACE activity, 4-6 h post-treatment, and urinary A:C on days -1, -2, 1, 4, and 7. There was a significant increase in the average urine aldosterone-to-creatinine ratio (UAldo:C) after administration of furosemide (P < 0.05). Enalapril inhibited ACE activity (P < 0.0001) but did not significantly reduce aldosterone excretion. A significant (P < 0.05) increase in the UAldo:C was maintained for the 7 days of the study in both groups. Enalapril decreased plasma ACE activity; however, it did not suppress furosemide-induced RAAS activation, as determined by the UAldo:C. While enalapril blunts ACE activity, the absence of circulating RAAS suppression may be due to angiotensin II reactivation, alternative RAAS pathways, and furosemide overriding concurrent ACE inhibition, all indicating the existence of aldosterone breakthrough (ABT). Along with similar findings with benazepril, it appears that failure to suppress aldosterone suppression with furosemide stimulation may be a drug class effect. The discrepancy between the current data and the documented benefits of enalapril likely reflects the efficacy of this ACE inhibitor in suppressing tissue RAAS, variable population responsiveness to ACE-inhibition, and/or providing additional survival benefits, possibly through as yet unknown mechanisms., (© 2015 John Wiley & Sons Ltd.)

Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P < 0.05). Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P < 0.05) but did not significantly reduce aldosterone excretion (Group FB baseline UAldo:C = 0.35, SD 0.16; day 1 UAldo:C = 0.79, SD 0.39; day 3 UAldo:C 0.92, SD 0.48, day 7 UAldo:C = 0.99, SD 0.48, P < 0.05). Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy., (© 2014 John Wiley & Sons Ltd.)

Objective: To assess survival time and adverse events related to the administration of pimobendan to cats with congestive heart failure (CHF) secondary to hypertrophic cardiomyopathy (HCM) or hypertrophic obstructive cardiomyopathy (HOCM)., Design: Retrospective case-control study., Animals: 27 cats receiving treatment with pimobendan and 27 cats receiving treatment without pimobendan., Procedures: Medical records between 2003 and 2013 were reviewed. All cats with HCM or HOCM treated with a regimen that included pimobendan (case cats) were identified. Control cats (cats with CHF treated during the same period with a regimen that did not include pimobendan) were selected by matching to case cats on the basis of age, sex, body weight, type of cardiomyopathy, and manifestation of CHF. Data collected included signalment, physical examination findings, echocardiographic data, serum biochemical values, and survival time from initial diagnosis of CHF. Kaplan-Meier survival curves were constructed and compared by means of a log rank test., Results: Cats receiving pimobendan had a significant benefit in survival time. Median survival time of case cats receiving pimobendan was 626 days, whereas median survival time for control cats not receiving pimobendan was 103 days. No significant differences were detected for any other variable., Conclusions and Clinical Relevance: The addition of pimobendan to traditional treatment for CHF may provide a substantial clinical benefit in survival time for HCM-affected cats with CHF and possibly HOCM-affected cats with CHF.

Background: Myocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families., Hypothesis/objectives: We hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion., Animals: Thirty-three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease., Methods: DNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fisher's exact test. T-tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%., Results: Thirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements., Conclusions and Clinical Importance: This study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Objective: To determine whether a high dosage of pimobendan, when administered concurrently with moderate-dosage furosemide to healthy dogs, would activate the renin-angiotensin-aldosterone system (RAAS) more than furosemide alone., Animals: 12 healthy dogs., Procedures: 6 dogs received furosemide (2.0 mg/kg, PO, q 12 h) only, as an RAAS activator, for 10 days. The other 6 dogs received furosemide (2.0 mg/kg, PO, q 12 h) and pimobendan (0.6 mg/kg, PO, q 12 h) for 10 days. The effect of these drugs on the RAAS was determined by measurement of the aldosterone-to-creatinine ratio (A:C) in urine collected in the morning and evening of study days -2, -1, 1, 5, and 10., Results: Although there was an increase in the urine A:C during the study period in both groups, it was significant only for dogs that received both drugs. The urine A:C only differed significantly between groups on day 1, at which time A:C was greater in the group that received both drugs., Conclusions and Clinical Relevance: High-dosage pimobendan administration neither substantially suppressed nor potentiated the RAAS when administered with furosemide in healthy dogs.

An adult Labrador retriever dog was presented with respiratory signs and heart murmur. Echocardiography and thoracic radiographs revealed a heart base mass infiltrating the left atrial wall. Microscopically, neoplastic tissues consisted of spindle cells and abundant extracellular matrix. Based on histochemical stain and immunohistochemistry, a diagnosis of primary cardiac sarcoma was made.

Case Description: 2 castrated male Labrador Retrievers (dogs 1 and 2) were evaluated 3 to 4 years after placement of a permanent pacemaker. Dog 1 was evaluated because of a large volume of chylous pleural effusion. Dog 2 was admitted for elective replacement of a pacemaker., Clinical Findings: Dog 1 had mild facial swelling and a rapidly recurring pleural effusion. Previously detected third-degree atrioventricular block had resolved. Cranial vena cava (CVC) syndrome secondary to pacemaker-induced thrombosis and stricture of the CVC was diagnosed on the basis of results of ultrasonography, computed tomography, and venous angiography. Dog 2 had persistent third-degree atrioventricular block. Intraluminal caval stricture and thrombosis were diagnosed at the time of pacemaker replacement. Radiographic evidence of pleural effusion consistent with CVC syndrome also was detected at that time., Treatment and Outcome: Dog 1 improved after treatment with unfractionated heparin and a local infusion of recombinant tissue-plasminogen activator. Balloon venoplasty was performed subsequently to relieve the persistent caval stricture. In dog 2, balloon dilatation of the caval stricture was necessary to allow for placement of a new pacing lead. Long-term anticoagulant treatment was initiated in both dogs. Long-term (> 6 months) resolution of clinical signs was achieved in both dogs., Clinical Relevance: Thrombosis and stricture of the CVC are possible complications of a permanent pacemaker in dogs. Findings suggested that balloon venoplasty and anticoagulation administration with or without thrombolytic treatment can be effective in the treatment of dogs with pacemaker-induced CVC syndrome.