RESUMEN
Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.
Asunto(s)
Modelos Animales de Enfermedad , Hipoglucemiantes , Síndrome Metabólico , Obesidad , Animales , Perros , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Glucemia/metabolismo , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Péptido Natriurético Encefálico/sangre , Péptido Natriurético Encefálico/metabolismo , Estrés Oxidativo/efectos de los fármacos , FemeninoRESUMEN
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.
Asunto(s)
Enfermedades de los Perros , Insuficiencia Cardíaca , Enfermedades de las Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Humanos , Perros , Animales , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/veterinaria , Válvula Mitral , Estudios Retrospectivos , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/veterinaria , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/veterinariaRESUMEN
OBJECTIVES: The aim of this study was to collect data from a substantial number of older cats having their systolic blood pressure (SBP) measured in a variety of clinical practices, to describe the findings and assess variables that affected the duration of assessment and the values obtained. METHODS: An international (European-based) multicentre convenience sample survey of cats ⩾7 years of age attending veterinary clinics and having SBP measured as part of their clinical assessment. Information gathered included details of the cat, concomitant disease(s) or therapies, SBP results, device used, time taken to assess SBP and the demeanor of the cat. RESULTS: Useable data were available from 8884 cats aged 7-26 years, from 811 clinics across 16 countries. The device used to measure SBP was Doppler in 47.4% and oscillometry in 48.5%. The demeanor of the cat was reported to be calm in 45.7%, anxious in 41.9% and nervous in 8.9%; and the duration of assessment was reported to be <5 mins in 50.4%, 5-10 minutes in 41.7% and >10 mins in 7.9%. Concomitant chronic kidney disease (CKD) was reported in 21.8%, hyperthyroidism in 12.0% or both in 3.1%. The median SBP was 150 mmHg (range 80-310), with 18.6% classified as hypertensive (SBP 160-179 mmHg) and 21.1% as severely hypertensive (SBP ⩾180 mmHg). The measured SBP was significantly affected by the cat's demeanor, duration of SBP assessment, presence of CKD and/or hyperthyroidism, the cat's sex and age, and the presence of concomitant therapy. The duration of SBP assessment was significantly affected by the cat's demeanor. CONCLUSIONS AND RELEVANCE: In veterinary clinics, SBP can be measured in most cats within a short period of time using either Doppler or oscillometric equipment. The presence of CKD or hyperthyroidism was associated with significantly higher SBP values, and anxious or nervous cats had higher SBP values and took longer to obtain SBP assessments.
Asunto(s)
Enfermedades de los Gatos , Hipertensión , Hipertiroidismo , Mercurio , Insuficiencia Renal Crónica , Animales , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea/veterinaria , Gatos , Hipertensión/complicaciones , Hipertensión/veterinaria , Hipertiroidismo/complicaciones , Hipertiroidismo/veterinaria , Atención Primaria de Salud , Insuficiencia Renal Crónica/veterinariaRESUMEN
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS), when chronically activated, is harmful and RAAS-suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people. HYPOTHESIS/OBJECTIVES: To determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE-I), benazepril, and spironolactone, would be superior to benazepril alone. ANIMALS: Five hundred and sixty-nine client-owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10-days' duration. METHODS: After initial stabilization, dogs were randomized into a positive-controlled, double-blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d. RESULTS: A significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32-0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59-0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups. CONCLUSION AND CLINICAL IMPORTANCE: The combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.
Asunto(s)
Enfermedades de los Perros , Insuficiencia Cardíaca , Animales , Benzazepinas , Enfermedades de los Perros/tratamiento farmacológico , Perros , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/veterinaria , Válvula Mitral , Espironolactona/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Torasemide is a potent loop diuretic with potential to treat congestive heart failure (CHF) in dogs. OBJECTIVE: Evaluate the efficacy and safety of torasemide compared to furosemide in dogs with first occurrence of CHF caused by degenerative mitral valve disease (DMVD). ANIMALS: Three hundred and nineteen dogs with new onset CHF attributable to DMVD. METHODS: Double-blinded randomized noninferiority study of PO torasemide vs furosemide in addition to standard CHF treatment. The primary efficacy criterion was decreased pulmonary edema and cough and no worsening of dyspnea or exercise tolerance at day 14. Secondary endpoints included clinical response at day 84 and time to death, euthanasia, or premature study withdrawal for cardiac reasons. RESULTS: Torasemide q24h (n = 161) was noninferior to furosemide q12h (n = 158); percentage of dogs meeting primary efficacy criterion at day 14 was similar between groups (torasemide, 74.4% [95% confidence interval (CI), 66.8%-81.0%] vs. furosemide, 73.5% [95% CI, 65.7%-80.4%]; risk ratio [RR], 1.01; 95% CI, 0.89-1.15; P = .87). Efficacy at day 84 showed similar results (RR, 1.05; 95% CI, 0.88-1.25; P = .6). Dogs receiving torasemide had a longer time to endpoint and were less than half as likely to experience death, euthanasia, or premature study withdrawal (hazard ratio, 0.36; 95% CI, 0.19-0.65; P = .001) than dogs receiving furosemide at any time during the study. CONCLUSION AND CLINICAL IMPORTANCE: Torasemide was noninferior to furosemide as first line PO treatment for new onset CHF caused by DMVD. Torasemide significantly decreased risk of cardiac-related death or premature study withdrawal for cardiac reasons compared to furosemide.
Asunto(s)
Enfermedades de los Perros , Insuficiencia Cardíaca , Animales , Diuréticos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Furosemida/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/veterinaria , Masculino , Válvula Mitral , Sulfonamidas/uso terapéutico , TorasemidaRESUMEN
BACKGROUND: Parturition and the initial postpartum period are important moments in the reproductive cycle of dogs. METHODS: A study assessed the effect of ADAPTIL, a dog-appeasing pheromone, on maternal behaviour during peripartum. Bitches were continuously exposed to ADAPTIL (n=20) or placebo (n=21) in double-blinded conditions from an average of about seven days before parturition up to 21 days postpartum. Differences in maternal behaviour in relation to the treatment were evaluated by the observation of specific activities through video recordings, such as the time spent by the bitch in close contact with the puppies, oronasal interaction and nursing duration and position. Videos were recorded at four time points (W0: within the first 48 hours of whelping; W1: one week after parturition; W2: two weeks after parturition; and W3: three weeks after parturition). In addition, the perception of breeders in relation to the quality of maternal care, puppies' wellbeing and overall relationship between the bitches and the puppies was evaluated using Visual Analogue Scale at the same time points. Moreover, the daily activity of the bitches was measured by using an electronic device (FitBark dog activity trackers, Kansas City, Missouri). RESULTS: For all observed maternal behaviours, there was a steady decrease in levels as the puppies developed, independently of treatment. However, bitches exposed to ADAPTIL tended to nurse significantly more in lying position, while those exposed to the placebo nursed more in a seated position, especially at W1 (P=0.06) and W3 (P=0.005). According to the breeders, the attention scores of bitches towards puppies were significantly higher in ADAPTIL than in the placebo group at each time point (P=0.01). Moreover, a difference according to parity was observed (P=0.004), with greater attention score displayed by primiparous bitches exposed to ADAPTIL compared with placebo on W0 (P=0.02), W1 and W3 (P<0.001). The global mother-puppies relationship was also perceived as significantly better (P=0.0002) by breeders of bitches exposed to ADAPTIL, with significant differences at W2 (P=0.01) and W3 (P=0.001). The bitches' daily activity increased starting two days before the whelp, peaked during parturition and then gradually declined up until four days postpartum. There was a trend towards a difference in the activity level according to the treatment during the full study period (P=0.09) and at two days before parturition (P=0.07). Bitches exposed to ADAPTIL were more active compared with placebo in relation to the FitBark data. CONCLUSION: The use of ADAPTIL in maternity modulated maternal behaviours. Concerning the caregiver's view, bitches under the influence of ADAPTIL had greater and extended attention towards the puppies and they were eager to stay with the puppies for a longer time.