Echocardiographic and hemodynamic effects of alfaxalone or dexmedetomidine based sedation protocols in cats with hypertrophic cardiomyopathy: a pilot study.

OBJECTIVE: To report the effects of alfaxalone and dexmedetomidine based sedation protocols on echocardiographic and hemodynamic variables in cats with hypertrophic cardiomyopathy (HCM) during sedation and inhalational anesthesia. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: A group of 10 client-owned cats with subclinical HCM. METHODS: Cats were administered one of two sedative intramuscular combinations: protocol ABM (alfaxalone 2 mg kg-1, butorphanol 0.4 mg kg-1, midazolam 0.2 mg kg-1; n = 5) or protocol DBM (dexmedetomidine 8 µg kg-1, butorphanol 0.4 mg kg-1, midazolam 0.2 mg kg-1; n = 5). General anesthesia was induced with intravenous alfaxalone and maintained with isoflurane in oxygen. Echocardiographic variables and noninvasive arterial blood pressures were obtained before sedation, following sedation, and during inhalational anesthesia. Sedation scores and alfaxalone induction dose requirements were recorded. Descriptive statistics are reported for cardiovascular variables. RESULTS: During sedation, echocardiographic and hemodynamic variables remained within normal limits with protocol ABM, whereas protocol DBM was characterized by bradycardia, low cardiac index and elevated blood pressure. During isoflurane anesthesia, both protocols demonstrated similar hemodynamic performance, with heart rates of 98 ± 12 and 89 ± 11 beats min-1, cardiac index values of 68 ± 17 and 47 ± 13 mL min-1 kg-1 and Doppler blood pressures of 72 ± 15 and 79 ± 20 mmHg with protocols ABM and DBM, respectively. A reduction in myocardial velocities were also observed during atrial and ventricular contraction with both protocols during isoflurane anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: An alfaxalone based protocol offered hemodynamic stability during sedation in cats with HCM; however, both dexmedetomidine and alfaxalone based protocols resulted in clinically relevant hemodynamic compromise during isoflurane anesthesia. Further studies are required to determine optimal sedative and anesthetic protocols in cats with HCM.

Hypertrophic Cardiomyopathy-Advances in Imaging and Diagnostic Strategies.

Hypertrophic cardiomyopathy (HCM) is the most important and prevalent cardiac disease in cats. Due to the highly variable nature of HCM, a multimodal approach including physical examination, genetic evaluation, cardiac biomarkers, and imaging are all essential elements to appropriate and timely diagnosis. These foundational elements are advancing rapidly in veterinary medicine. Newer biomarkers such as galectin-3 are currently being researched and advances in tissue speckle-tracking and contrast-enhanced echocardiography are readily available. Advanced imaging techniques, such as cardiac MRI, are providing previously unavailable information about myocardial fibrosis and paving the way for enhanced diagnostic capabilities and risk-stratification in cats with HCM.

Cardiac Magnetic Resonance Imaging Detects Myocardial Abnormalities in Naturally Infected Dogs with Chronic Asymptomatic Chagas Disease.

Trypanosoma cruzi infection causes inflammation and fibrosis, resulting in cardiac damage in dogs. The objectives of this study were to describe cardiac magnetic resonance imaging (CMR) in naturally infected dogs with chronic Chagas disease and the frequency of abnormalities for CMR and cardiac diagnostic tests. Ten asymptomatic, client-owned dogs seropositive for T. cruzi were prospectively enrolled in an observational study evaluating echocardiography, ECG (standard and ambulatory), cardiac troponin I (cTnI), and CMR. Standard ECG measurements (3/10) and cTnI concentration (1/10) outside the reference range were uncommon. Ambulatory ECG abnormalities were documented more frequently (6/10 dogs) than with standard ECG and included ventricular arrhythmias (4), supraventricular premature beats (3), second-degree atrioventricular block (2), and sinus arrest (1). Echocardiographic abnormalities were documented in 6/10 dogs including mildly increased left ventricular internal dimension in diastole (1) and decreased right ventricular (RV) systolic function based on reductions in tricuspid annular plane systolic excursion (3) and RV S' (4). Abnormalities were detected with CMR in 7/10 dogs including delayed myocardial enhancement in 5 of which 2 also had increased extracellular volume, abnormal wall motion in 5, and loss of apical compact myocardium in 1. In conclusion, CMR abnormalities were common, and the results of this study suggest CMR can provide useful information in dogs with T. cruzi infection and may support naturally infected dogs for future clinical investigation as an animal model for Chagas disease.

Ala vestibuloplasty improves cardiopulmonary and activity-related parameters in brachycephalic cats.

OBJECTIVE: To evaluate the effects of ala vestibuloplasty on cardiopulmonary and lifestyle-related parameters in brachycephalic (BC) cats. STUDY DESIGN: Prospective cohort. ANIMALS: Client-owned BC cats (n = 19). METHODS: Cats were assessed preoperatively by airway computed tomography (CT), endoscopy, contrast echocardiography, cardiac biomarkers, and structured owner questionnaire. Ala vestibuloplasty was performed bilaterally, and blood values, imaging, and owner questionnaire responses were re-evaluated 8-20 weeks postoperatively. RESULTS: Cats were presented for predominantly respiratory clinical signs attributable to brachycephaly. Preoperatively, all cats had stenotic nares, prolonged normalized pulmonary transit time (nPTT) (mean 5.43 ± 1.10 s), and a hyperattenuating pulmonary pattern. No complications occurred following surgery. Postoperatively, nPTT (mean 3.89 ± 0.74 s, p < .001) and frequencies of sneezing (p = .002), snoring (p = .006), open-mouth breathing (p = .0004), and nasal discharge (p = .019) were decreased. Cats exhibited increased activity (p = .005), less frequent dyspnea during activity (p < .001), longer duration of activity before becoming dyspneic (p = .002), faster recovery from activity (p < .001), and decreased respiratory noise (p < .001). Median questionnaire scores improved from preoperative to postoperative (p < .001). CONCLUSION: Anatomic, echocardiographic, and CT changes were common in this cohort of clinically affected BC cats. Pulmonary blood flow and respiratory function were improved after surgery. CLINICAL SIGNIFICANCE: Stenotic nares are the predominant airway abnormality in BC cats. Ala vestibuloplasty is a safe procedure that improves cardiac and CT abnormalities and respiratory and other clinical signs in BC cats.

Use of alfaxalone in bearded dragons (Pogona vitticeps): optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography.

OBJECTIVE: Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for procedures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has been performed in squamate species using alfaxalone without preservatives at various doses and routes of administration, but it is unknown whether preservatives affect quality of sedation or cardiac function. ANIMALS: 10 bearded dragons. PROCEDURES: This complete crossover study evaluated the pharmacodynamic effects of alfaxalone with preservatives administered to bearded dragons via intracoelomic (ICo; n = 10), SC (10), IM (9), and IV (9) injection at 15 mg/kg. RESULTS: Deep sedation was achieved in 9 of 10 ICo, 8 of 10 SC, 8 of 9 IM, and 9 of 9 IV administrations. Heart rate significantly decreased from baseline for ICo (P = .008; median heart rate, 46), IM (P = .018; 54), and IV (P = .033; 54) routes, but maintained within clinically acceptable limits. Respiratory rate significantly decreased from baseline for ICo (P = .011; median respiratory rate, 30), SC (P = .024; 12), IM (P = .028; 12), and IV (P = .043; 12) routes. Spontaneous ventilation was retained during all events. Time to first effects was significantly sooner with IV (0 min) administration compared with ICo (P = .02; 5 min) and IM (P = .008; 5 min). Time to loss and recovery of withdrawal, righting reflex, deep pain, and purposeful movement were not significantly different between routes of administration. End-systolic volume was the only echocardiographic parameter significantly affected by IV sedation. CLINICAL RELEVANCE: Sedation quality was most consistent via IV administration at 15 mg/kg, and minimal changes in cardiac function were observed.

Canine urinary lactate and cortisol metabolites in hypercortisolism, nonadrenal disease, congestive heart failure, and health.

Spontaneous hypercortisolism (HC) is a common endocrine disease of senior dogs, often overlapping in selected clinical signs and hematologic and blood biochemical abnormalities with nonadrenal diseases (NADs). HC and NAD could differentially affect cortisol metabolism, which is a complex 10-enzymatic pathway process. HC might also affect blood and urine lactate levels through its effects on mitochondrial function. We aimed to differentiate between HC and NAD via a urinary cortisol metabolites and lactate panel. We prospectively recruited 7 healthy dogs and 18 dogs with HC, 15 with congestive heart failure (CHF), and 9 with NAD. We analyzed urine by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. We normalized urinary lactate and cortisol metabolites to urine creatinine concentration, and then compared groups using a linear-mixed model and principal component (PC) analysis. A machine-learning classification algorithm generated a decision tree (DT) model for predicting HC. The least-squares means of normalized urinary 6ß-hydroxycortisol and PC1 of the HC and CHF groups were higher than those of the healthy and NAD groups (p = 0.05). Creatinine-normalized urinary 6ß-hydroxycortisol had better sensitivity (Se, 0.78; 95% CI: 0.55-0.91), specificity (Sp, 0.89; 95% CI: 0.57-0.99), and a likelihood ratio (LR; 7), than the Se (0.72; 95% CI: 0.49-0.88), Sp (0.89; 95% CI: 0.57-0.99), and LR (6.5) of PC1 for distinguishing HC from NAD. Lactate and dihydrocortisone had the highest decreasing node-weighted impurity value and were considered the most important features in the DT model; dihydrocortisol had no role in determining whether a dog had HC.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Cats With Hypertrophic Cardiomyopathy.

Objective: To assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) for cardiac death in cats with hypertrophic cardiomyopathy. Study Design: Prospective observation study. Animals: Ninety-six client-owned cats. Methods: Complete blood count samples were collected from 38 healthy and 58 cats with hypertrophic cardiomyopathy (HCM), and the NLR ratios were analyzed. All cats had echocardiographic measurements performed on the same day as blood collection. Spearman rank correlation was used to assess the relationship between echocardiographic measurements and NLR. Long-term outcome data were obtained, and time to cardiac death and variables associated with cardiac death were analyzed using Kaplan-Meier survival curves and Cox proportional hazards models, respectively. Results: The NLR was significantly higher in cats with confirmed congestive heart failure. When evaluating HCM patients, cats in the third NLR tertile had a significantly higher risk of cardiac death with a hazard ratio of 10.26 (95% CI: 1.84-57.14; p = 0.0001) when compared with that of patients in the first tertile. NLR was significantly associated with echocardiographic measures of left atrial size, left auricular function, the presence of left atrial spontaneous echo contrast (SEC), and thrombus formation. Conclusions and Clinical Relevance: Increased NLR is a negative prognostic indicator in cats with HCM.

Comparison of in-hospital continuous electrocardiography versus recordable Holter monitoring in dogs with ventricular arrhythmias.

OBJECTIVE: Determine the agreement between nonrecordable continuous ECG and Holter monitoring at estimating arrhythmia severity in hospitalized dogs. DESIGN: Prospective, observational, cohort study. SETTING: University teaching hospital. ANIMALS: Ten dogs. INTERVENTIONS: Heart rates and rhythms were simultaneously monitored using nonrecordable cage-side continuous ECG and Holter monitoring. Continuous ECG was assessed by ICU technicians for 1 min every hour, and heart rate and rhythm were recorded. A modified Lown score was used to grade arrhythmia severity (Grade 0 = sinus; Grade 1 = single ventricular premature complexes; Grade 2 = accelerated idioventricular; Grade 3 = bigeminy/trigeminy; Grade 4 = couplets/triplets; Grade 5 = ventricular tachycardia or R on T). Holter data were analyzed by a board-certified cardiologist, and arrhythmia grade was assigned to the same 1-min time period reported by ICU technicians. A 1-h arrhythmia grade was also determined from Holter data and was reported as the highest grade noted during the previous hour. Cohen's weighted kappa analysis was used to compare the agreement of ICU and Holter grade during the same 1-min time period and to compare 1-min Holter grade with the prior hour Holter grade. MEASUREMENTS AND MAIN RESULTS: Weak agreement was found between ICU-reported grade and Holter grade (κ = 0.40), as well as weak agreement between 1-min Holter grade and hour Holter grade (κ = 0.39). CONCLUSIONS: Results of this study indicate that arrhythmia grades assessed by ICU technicians and hourly 1-min observations weakly agree with recordable Holter monitoring in hospitalized dogs with ventricular arrhythmias.

Multidose pharmacokinetics and safety of a modified, compounded theophylline product in dogs.

Theophylline is used in canine medicine for the management of chronic bronchitis and bradyarrhythmias, yet no species-validated commercial products are available. This study reports the single-dose and multidose pharmacokinetics and safety of a modified, compounded theophylline (MCT) product readily available from a well-established, USP-compliant compounding pharmacy, which may be a suitable and reliable source for theophylline for dogs. Eleven dogs underwent serial plasma theophylline measurement following 10 mg/kg MCT PO. After a 7 days washout, dogs received 10 mg/kg MCT PO q12h and serial plasma theophylline quantification was repeated after the ninth dose. Dogs were monitored for potential adverse effects. For the nine dogs that completed the study, plasma theophylline concentrations were between 5 and 30 µg/ml for 91 +/- 15% of the dosing interval. There was no significant difference in half-life between single-dose and multidose administration. The most common adverse effects reported were mild and included agitation, excitement, and increased activity. The results of this study support the use of 10 mg/kg MCT administered twice daily as a starting dosage in dogs. This regimen appears safe, achieves appropriate plasma drug concentrations in most dogs, and does not cause significant changes in pharmacokinetic properties at steady state. Because compounded drugs do not undergo consistent testing for identity, quality, strength, purity, and stability, results of research described in reports using compounded products may not be reproducible.

EFFECT OF BODY POSITION ON ECHOCARDIOGRAPHIC PARAMETERS IN PRAIRIE RATTLESNAKES (CROTALUS VIRIDIS).

Echocardiography is a noninvasive diagnostic tool that can provide instantaneous information about cardiac function, but it is uncommonly used by veterinarians to assess reptilian patients. Echocardiograms were performed on 14 clinically healthy, adult prairie rattlesnakes (Crotalus viridis), and cardiac measurements were taken in a horizontal and vertical position. Cardiac parameters including ventricular volume in systole and diastole, as well as the diameter of the left atrium, pulmonary artery, and paired left and right aortic arches were obtained. No evidence of cardiac disease was noted in any of the study animals. Males had a greater percentage of ventricular volume change (VVC) than females in the vertical position (P = 0.043). The percentage of ventricular volume change was significantly lower in the horizontal compared with the vertical position (P = 0.032) and was not different by sex. For the short-axis views, the right atrial diameter and short-axis ventricular area in diastole and systole were significantly smaller in snakes in the vertical compared with the horizontal position. This study is the first to obtain echocardiographic measurements in North American vipers and adds to the understanding of techniques used to evaluate the cardiac function of these species.

Pharmacokinetics and pharmacodynamics of intravenous and oral apixaban in horses.

Large vessel and microvascular thrombi are common complications in systemically ill horses contributing to patient morbidity and mortality. Apixaban, an oral factor Xa inhibitor, shows excellent efficacy against stroke and deep vein thrombosis in humans. The purpose of this study was to determine serum apixaban concentrations and anti-factor Xa activity in horses after orally administered apixaban. Five horses received a single dose of intravenous (0.09 mg/kg) and oral (1 mg/kg) apixaban in a cross-over design. Serum apixaban concentrations and anti-Xa activity were measured serially via liquid chromatography-tandem mass spectrometry and a commercial assay, respectively, for 12 hr following oral administration. Apixaban was detected in all horses after both oral and intravenous administration. Oral administration yielded a mean maximum concentration of 60.3 ng/ml (59.4-111 ng/ml), mean time to maximum concentration of 0.5 hr (0.5-2), mean half-life of 6.2 hr (4.6-8.3), and mean oral bioavailability of 10% (3.8-17.4). After oral administration, anti-Xa activity had a strong positive relationship with serum apixaban and was best represented by a dose-response model with the following parameters: E0  = 5.00 ng/ml, EMAX  = 311 ng/mL, EC50  = 267 ng/ml, and n = 1.58. Anti-Xa activity was significantly higher 2 hr post-administration compared with baseline (p = .032). Despite low oral bioavailability, administration of 1 mg/kg oral apixaban, in healthy horses, achieves serum concentrations similar to those reported in humans. Apixaban has potential clinical utility in horses and warrants further investigation.

Cardiac extracellular volume fraction in cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) allows for detection of fibrosis in hypertrophic cardiomyopathy (HCM) by quantification of the extracellular volume fraction (ECV). HYPOTHESIS/OBJECTIVES: To quantify native T1 mapping and ECV in cats. We hypothesize that native T1 mapping and ECV will be significantly increased in HCM cats compared with healthy cats. ANIMALS: Seventeen healthy and 12 preclinical HCM, age-matched, client-owned cats. METHODS: Prospective observational study. Tests performed included indirect blood pressure, CBC, biochemical analysis including total thyroid, urinalysis, transthoracic echocardiogram, and CMR. Cats were considered healthy if all tests were within normal limits and a diagnosis of HCM was determined by the presence of left ventricular concentric hypertrophy ≥6 mm on echocardiography. RESULTS: There were statistically significant differences in LV mass (healthy = 5.87 g, HCM = 10.3 g, P < .0001), native T1 mapping (healthy = 1122 ms, HCM = 1209 ms, P = .004), and ECV (healthy = 26.0%, HCM = 32.6%, P < .0001). Variables of diastolic function including deceleration time of early diastolic transmitral flow (DTE), ratio between peak velocity of early diastolic transmitral flow and peak velocity of late diastolic transmitral flow (E : A), and peak velocity of late diastolic transmitral flow (A wave) were significantly correlated with ECV (DTE; r = 0.73 P = .007, E : A; r = -0.75 P = .004, A wave; r = 0.76 P = .004). CONCLUSIONS AND CLINICAL IMPORTANCE: Quantitative assessment of cardiac ECV is feasible and can provide additional information not available using echocardiography.

OPTIMIZING THE PHARMACODYNAMICS AND EVALUATING CARDIOGENIC EFFECTS OF THE INJECTABLE ANESTHETIC ALFAXALONE IN PRAIRIE RATTLESNAKES (CROTALUS VIRIDIS).

North American vipers are commonly housed in zoological institutions or studied as free-ranging populations. Because of their venomous predatory and defensive mechanism, sedation or anesthesia is frequently employed to facilitate safe handling and medical procedures, especially of the head. A new formulation of alfaxalone with proprietary preservatives was recently approved and indexed for 28-d use post-vial puncture. Pharmacodynamic effects of alfaxalone in its prior formulation have been researched in nonvenomous species, but the optimal dose and route of administration in vipers have not been reported. In part one, 10 prairie rattlesnakes (Crotalus viridis) participated in a complete four-route crossover study evaluating 20 mg/kg alfaxalone administered intracoelomically (ICo), SC cranial to the heart, IM cranial to the heart, and IV in the ventral coccygeal vein. HR significantly decreased from baseline during IV (P= 0.024), IM (P= 0.024), and SC (P= 0.028) administration. Respiratory rate significantly decreased following alfaxalone delivered IV (P = 0.027). Time to first effects was significantly faster in IV compared with IM (P= 0.01), SC (P= 0.001), and ICo (P= 0.036). All IV and IM administrations resulted in deep sedation, but 70% of the IV and 10% of the IM sedation events resulted in apnea and required intermittent positive ventilation via endotracheal tube. Fifty percent of the ICo sedation events and 10% of the SC sedation events did not result in sedation. One successful SC sedation event resulted in apnea. In part two, echocardiograms were performed in the same rattlesnakes at baseline and at maximum effect of sedation with 20 mg/kg alfaxalone administered IM. Cardiac contractility and output were unaffected. Administration of alfaxalone at 20 mg/kg IM cranial to the heart should facilitate safe handling and minimally invasive procedures in prairie rattlesnakes and related species.

Effect of Methadone or Hydromorphone on Cardiac Conductivity in Dogs Before and During Sevoflurane Anesthesia.

Objective: To evaluate changes in electrocardiogram (ECG) variables in healthy dogs receiving either methadone or hydromorphone IV before and during sevoflurane anesthesia. Study Design: Prospective clinical study. Animals: Forty client-owned dogs. Methods: Dogs were randomized to receive methadone 0.5 mg/kg IV or hydromorphone 0.1 mg/kg IV in each part of a two-part study. In part one, dogs received the opioid prior to sevoflurane anesthesia (groups MS, n = 12 and HS, n = 12). Anesthesia was induced with propofol IV, maintained with sevoflurane, and dogs were mechanically ventilated. Standard 6-lead ECG recordings were obtained before opioid administration, 2, 5, and 10 min after opioid administration prior to anesthesia, and during anesthesia 15 min after end-tidal sevoflurane stabilized at 2.4%. In part two, conscious dogs received the same opioid treatments and ECGs were obtained at equivalent time points without undergoing anesthesia (groups M, n = 8 and H, n = 8). Values for ECG variables were determined by a blinded cardiologist and included: Heart rate (HR), PR interval, QT interval, and HR corrected QT interval (QTc) using the Bazett (QTcB), Fridericia (QTcF), and Van de Water (QTcV) formulas. Differences over time and between all four groups were evaluated using ANOVA for repeated measures with significance set at p ≤ 0.05. Results: Both methadone and hydromorphone administration reduced HR and prolonged PR and QT intervals, with greater changes observed during sevoflurane anesthesia. The greatest prolongation in QT interval was observed in dogs administered methadone during sevoflurane anesthesia. Conclusions and Clinical Relevance: Methadone and hydromorphone caused disturbances in myocardial electrical activity, and the addition of sevoflurane enhanced these disturbances. Both drugs caused considerable QT interval prolongation into the proarrhythmogenic range, with methadone causing greater prolongation.

Quantitative assessment of left ventricular volume and function by transthoracic and transesophageal echocardiography, ultrasound velocity dilution, and gated magnetic resonance imaging in healthy foals.

OBJECTIVE: To compare measurements of left ventricular volume and function derived from 2-D transthoracic echocardiography (2DE), transesophageal echocardiography (TEE), and the ultrasound velocity dilution cardiac output method (UDCO) with those derived from cardiac MRI (cMRI) in healthy neonatal foals. ANIMALS: 6 healthy 1-week-old Standardbred foals. PROCEDURES: Foals were anesthetized and underwent 2DE, TEE, and cMRI; UDCO was performed simultaneously with 2DE. Images acquired by 2DE included the right parasternal 4-chamber (R4CH), left apical 4- and 2-chamber (biplane), and right parasternal short-axis M-mode (M-mode) views. The longitudinal 4-chamber view was obtained by TEE. Measurements assessed included left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction, stroke volume (LVSV), cardiac output (CO), and cardiac index (CI). Bland-Altman analyses were used to compare measurements derived from biplane, R4CH, and M-mode images and UDCO with cMRI-derived measurements. Repeatability of measurements calculated by 3 independent reviewers was assessed by the intraclass correlation coefficient. RESULTS: Compared with cMRI, all 2DE and TEE modalities underestimated LVEDV and LVESV and overestimated ejection fraction, CO, and CI. The LVSV was underestimated by the biplane, R4CH, and TEE modalities and overestimated by UDCO and M-mode methods. However, the R4CH-derived LVSV, CO, and CI were clinically comparable to cMRI-derived measures. Repeatability was good to excellent for measures derived from the biplane, R4CH, M-mode, UDCO, and cMRI methods and poor for TEE-derived measures. CONCLUSIONS AND CLINICAL RELEVANCE: All assessed modalities yielded clinically acceptable measurements of LVEDV, LVESV, and function, but those measurements should not be used interchangeably when monitoring patient progress.

Plasma and tissue angiotensin-converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a homologue of angiotensin-converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1-9 and 1-7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty-nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1-12.1) as compared to control (2.2 mU/mg; IQR, 1.8-3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1-7, in dogs with CHF (486.7 pg/mL; IQR, 214.2-1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4-45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1-25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1-9 (preincubation, 10.3 pg/mL; IQR, 4.4-37.2; postincubation, 2431 pg/mL; IQR, 1355-3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6-226.4; postincubation, 2.4 pg/mL; IQR, 0.50-5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.

Effects of oral trazodone on echocardiographic and hemodynamic variables in healthy cats.

OBJECTIVES: The purpose of this study was to evaluate the effects of oral trazodone on echocardiographic variables, heart rate (HR) and blood pressure (BP) in healthy cats. METHODS: Client-owned domestic cats between 2 and 8 years of age were recruited. Cats were considered healthy based on physical examination, complete blood count, blood chemistry profile, urinalysis, total thyroxine concentration, non-invasive BP measurement by Doppler method and a screening transthoracic echocardiogram with simultaneous electrocardiogram. Echocardiographic variables assessed pre-trazodone and 90-120 mins post-trazodone (50 mg PO) included left ventricular internal diameter in systole and diastole, interventricular septal and left ventricular free-wall thickness in systole and diastole, left atrial size, left auricular function and left ventricular diastolic function assessed by spectral Doppler transmitral and pulmonary venous flow velocities, and tissue Doppler profiles. Mean echocardiographic and hemodynamic variables were calculated for pre- and post-trazodone examinations for each cat. Pre- and post-trazodone variables were analyzed with a paired t-test with significance set at P <0.05. RESULTS: Twelve healthy cats were evaluated. Trazodone was administered to all cats and a sedative effect was observed. There were no clinically significant differences in any echocardiographic variables post-trazodone administration. Systolic BP was significantly decreased after trazodone (P = 0.001) with no significant change in HR. CONCLUSIONS AND RELEVANCE: Trazodone did not alter echocardiographic variables, in a clinically relevant manner, in this group of healthy cats. Trazodone may aid in obtaining transthoracic echocardiograms without affecting HR or echocardiographic variables but may significantly lower BP in healthy cats.