Search Results (13)

Background: Some dogs with severe mitral valve regurgitation can have chronic cough, but its cause is unclear. Many of these dogs exhibit left principal (synonym mainstem) bronchial collapse or compression. Some clinicians believe that an enlarged heart, particularly the dilated left atrium, compresses the left principal bronchus, while others argue that a healthy bronchus cannot be compressed and that the cough is due to concurrent airway disease, such as bronchomalacia. In this study, we aimed to investigate the correlation between chronic cough and radiographic signs of bronchial narrowing in dogs with cardiomegaly secondary to primary mitral valve regurgitation. Methods: Four radiologists independently evaluated 51 sets of thoracic radiographs from client-owned dogs with cardiomegaly due to severe mitral valve regurgitation, including 26 sets of radiographs belonging to dogs with chronic (>8 weeks) cough and 25 without cough. The presence or absence of bronchial narrowing was assessed while the radiologists were blinded to patient characteristics and each other’s findings. Results: Interobserver variability was high, and the radiologists could not reliably predict which dogs had a chronic cough. Dogs with left atrial enlargement and airway narrowing sometimes coughed and sometimes did not. Likewise, some dogs with left atrial enlargement but no signs of airway compression or collapse coughed, and some did not. It was impossible to distinguish the groups based on these features. Conclusions: Bronchial compression by an enlarged heart and left atrium is an unlikely cause of chronic cough in dogs with severe primary mitral valve regurgitation. Full article

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a fatal disease in cats characterized by variable manifestations. Myocarditis represents a less commonly described pathology within the clinical spectrum of FIP. No research has described the successful treatment of FIP-induced myocarditis. In this study, 40 cats were included and treated with 15 mg/kg of GS-441524 every 24 h orally. All cats were diagnosed with FIP by reverse transcription quantitative PCR in effusion in combination with typical clinical and laboratory changes. Echocardiography was performed in all cats, and myocarditis was suspected in 4/40 cats. Equivocal wall thickness was diagnosed in 2/4 cats, while systolic dysfunction with biatrial dilation was diagnosed in the other 2/4 cats. One cat also presented with ventricular ectopy. A severe increase in cardiac troponin I was seen in all four cats (median 1.82 ng/mL (1.20–5.84 ng/mL)). Cardiac dimensions and electrocardiographic abnormalities completely normalized in all four cats during treatment with GS-441524 and remained stable after treatment discontinuation during a one-year follow-up period. Myocarditis can be a clinical feature of FIP and present with different cardiologic manifestations. FIP-induced myocarditis can be cured with GS-441524 in combination with symptomatic cardiovascular treatment including pimobendan, clopidogrel, furosemide, or atenolol, depending on the clinical presentation. Full article

Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization. Full article

The present study aimed to evaluate the effects of chronic pimobendan monotherapy on cardiac size in dogs with stage B2 myxomatous mitral valve disease (MMVD). Data from 31 dogs diagnosed with MMVD and cardiomegaly (LA/Ao ≥ 1.6 and LVIDdn ≥ 1.7) were included. The intervention group were dogs treated with pimobendan (n = 24). Dogs not receiving any cardiac medication were controls (n = 7). Echocardiographic changes in left atrial and left ventricular dimensions were compared over time. There was significant group × time interaction for LVIDdN (p = 0.011) between diagnosis and initial follow-up (median 3–6 months). There was a significant reduction in LVIDdN over time in the pimobendan group (p = 0.038) but not in the control group (p = 0.216). There was no significant group × time interaction for LA/Ao, and there was no effect of group (p = 0.561), but LA/Ao in both groups decreased over time (p = 0.01). Restraint is advised when prescribing pimobendan based on the detection of a heart murmur where echocardiographic staging is an option. Some stage B2 dogs that received pimobendan no longer met the echocardiographic classification criteria for stage B2 MMVD and could have been misclassified as stage B1 and had their medication inappropriately withdrawn. We suggest these dogs are referred to as reverse remodelled stage B2. Full article

The prognostic and diagnostic role of some trace elements in heart diseases has been demonstrated. In this study, the effects of min. 30-day and min. 120-day treatment with pimobendan, enalapril, and furosemide, as monotherapy and in combination, on serum trace element levels in dogs with heart failure were evaluated. A total of 107 dogs were treated with pimobendan or enalapril as monotherapy and pimobendan + enalapril (PE), enalapril + furosemide (EF), or pimobendan + enalapril + furosemide (PEF) as combination therapy for a min. of 30 and 120 days. Serum copper (Cu), zinc (Zn), iron (Fe), cobalt (Co), magnesium (Mg), manganese (Mn), selenium (Se), and chromium (Cr) were measured by an inductive coupled plasma optical emission spectroscopy device. Mean serum Mg in dogs treated with pimobendan for a min. of 120 days was significantly lower than that for a min. of 30 days (p < 0.05). In dogs using the PEF combination, mean serum Fe was significantly higher in the min. 120-day treatment group than in the min. 30-day treatment group (p < 0.01). No significant difference was observed in mean serum Cu, Zn, Co, Mn, Se, or Cr between the treatment groups and the time periods (p > 0.05). The short- and long-term use of pimobendan, enalapril, furosemide, and their combinations may cause changes in mean serum Mg and Fe in dogs with heart failure. Full article

Background: Myxomatous mitral valve degeneration is the most common canine heart disease. Several clinical trials have investigated various treatments. The latest recommendations are published in the ACVIM consensus guidelines (2019). Our study aimed to investigate how closely veterinary practitioners apply the treatment recommendations of these guidelines and the latest clinical trials. Methods: An online survey was sent to Dutch and Belgian veterinary practices via digital channels. Results: The data from 363 fully completed surveys were analyzed. For stage B1 disease, 93% recommended, correctly, no treatment. For stage B2 disease, 67% of the respondents recommended starting pimobendan as monotherapy. For chronic treatment of stage C disease, 16 different drug combinations were mentioned, but nobody recommended surgery. Only 48% of the respondents recommended the only evidence-based drug combination: a loop diuretic with pimobendan. A concerning finding was the simultaneous prescription of two loop diuretics, by 19% of the respondents. Conclusions: Treatment recommendations showed an increasing variation with more advanced disease stages from B1 through B2 to C. This reflects the increasing disagreement among the panelists who prepared the ACVIM consensus guidelines. Practitioners of our study seem to practice more evidence-based medicine than veterinary cardiologists, as it was reported in a recent survey-based study. Full article

Background: ACVIM developed and published guidelines for staging myxomatous mitral valve degeneration in dogs in 2009. An updated version was published in 2019. The present study aimed to investigate whether these guidelines are actually used by the intended public more than a decade after their first publication. Methods: An online survey was distributed among Dutch and Belgian veterinarians through online channels and mailing lists. Results: Of the 524 responses, only 363 complete surveys were analyzed. The ACVIM guidelines are used by 60% of the respondents. Veterinarians find it more difficult to differentiate stage B1 from B2 in asymptomatic dogs compared to diagnosing stage C. Three-quarters of the respondents would recommend echocardiography for an incidentally detected new murmur with an intensity of 3 out of 6 in an adult dog. Two-thirds of the respondents find coughing a convincing finding for stage C disease. Close to half of the respondents associate a horizontal, dull percussion line with pulmonary edema. For confirming cardiogenic pulmonary edema, 98% of the respondents used thoracic radiographs. Conclusions: Veterinary practitioners might not have the expected training and equipment to be able to apply the guidelines in their practices, especially in the differentiation of stage B1 from stage B2. Full article

Background: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. Methods: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. Results: The new method moderately correlated with LA:Ao (r = 0.56–0.66) in all groups. The diagnostic accuracy (72–74%) of the subjective assessment and the new method showed no difference. Conclusions: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation. Full article

Pimobendan is an inotropic and vasodilator drug with no sympathomimetic effects. This study aimed to evaluate the haemodynamic effects of pimobendan during anaesthesia in healthy senior dogs. A prospective, randomised, triple-blinded, placebo-controlled clinical study was conducted. Thirty-three dogs (median [range]: 9 [7, 12] years) were anaesthetised for surgical procedures. The dogs were randomly allocated into two groups: eighteen dogs received intravenous pimobendan at a dose of 0.15 mg/kg (PIMOBENDAN), and fifteen dogs received intravenous saline solutions at a dose of 0.2 mL/kg (PLACEBO). Data were recorded before, 1 min, 10 min, and 20 min after injection. Velocity-time integral (VTI), peak-velocity (PV), and mean-acceleration (MA) were measured using an oesophageal Doppler monitor (ODM). Heart rate and mean arterial pressure were also registered. The data were analysed using a two-way ANOVA for trimmed means. Statistical differences were considered if p < 0.05. Twenty minutes after injection, the VTI (13.0 cm [10.4, 22.3]), PV (95.0 [83.0, 160] m/s), and MA (12.6 [9.40, 17.0] m/s²) were significantly higher in the PIMOBENDAN group compared to the PLACEBO group (VTI: 10.5 [6.50, 17.4] cm, PV: 80.0 [62.0, 103] m/s and MA: 10.2 [7.00, 16.0] ms²). No significant differences were observed in the rest of the variables. Using pimobendan during anaesthesia increases VTI, PV, and MA, as measured by an ODM. Full article

Pulmonary hypertension (PH) is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol is an intravenous pulmonary vasodilator used to treat PH in humans; however, its efficacy in dogs remains unknown. We investigated the cardiovascular effects of epoprostenol and several cardiac agents for acute heart failure in canine models of chronic PH. Six dogs with chronic PH were anesthetized and underwent right heart catheterization and echocardiography before and after infusion of epoprostenol, dobutamine, dopamine and pimobendane. (The drug administration order was the same for all dogs). High-dose epoprostenol (15–20 ng/kg/min) tended to decrease pulmonary arterial pressure (PAP) while significantly decreasing pulmonary and systemic vascular resistance and increasing left and right ventricular (LV and RV, respectively) function. Pimobendan significantly increased LV and RV functions without increasing PAP. Conversely, dobutamine and dopamine significantly increased LV and RV function as well as PAP. This study revealed the efficacy of epoprostenol in treating canine PH through its pulmonary and systemic vasodilating effects. Although catecholamines improve LV and RV function, they might worsen PH pathophysiology, and careful monitoring may be necessary when using these drugs. Pimobendan improved LV and RV function without increasing PAP; however, a stronger vasodilating effect was observed with epoprostenol. Full article

An 11-year-old intact female Papillion weighing 2.1 kg was referred to our institution with the main complaint of shallow, rapid breathing. At the first visit (day 0), although clinical signs improved due to the use of medication from the primary hospital, transthoracic radiography and echocardiography revealed left heart enlargement and left ventricular dysfunction. A clinical diagnosis of dilated cardiomyopathy (DCM) was made and oral administration of pimobendan, temocapril, and taurine was initiated. However, on day 10, the respiratory status worsened and furosemide was prescribed. On day 54, no significant improvement in heart size was observed. Additionally, the diet that this patient received met the recommendation for diet-related DCM by the U.S. Food and Drug Administration, and the patient’s diet was changed from a grain-free diet to a grain-containing diet. On day 1191, the patient’s respiratory status was stable and no clinical signs were observed. Transthoracic radiography and echocardiography revealed an improvement in left heart size. Additionally, improvements in the left and right ventricular myocardial strains were observed after changing the diet. We suggest that it may be necessary to suspect a dietary association with dilated cardiomyopathy, and a good prognosis might be expected by dietary modification, even in small-breed dogs. Full article

The aims of this study were to investigate the effects of repeated and multiple-dose pimobendan on cardiac systolic function and the correlations between changes in cardiac systolic function and plasma concentrations of pimobendan and O-desmethylpimobendan (ODMP). Five clinically healthy cats were subjected to four different medication protocols for 14 days, with a washout period of at least 1 month between each protocol. The protocols were pimobendan 0.5 mg/kg q12h (high dosage [HD] group); pimobendan 0.25 mg/kg q12h (standard dosage [SD] group); pimobendan 0.125 mg/kg q12h (low dosage group); and Biofermin R, one tablet q12h (placebo group). Echocardiography and measurement of plasma concentrations of pimobendan and ODMP were performed prior to medication administration (baseline) and 20, 40, 60, 120, 240, 360, and 480 min after administration, and the correlation between the changes in cardiac systolic function and plasma concentration of pimobendan, ODMP, or the sum of both were examined. The cardiac systolic function increased in the HD and SD groups, and there were significant correlations between the lateral peak systolic myocardial velocity (S′) changes and plasma pimobendan, plasma ODMP, and the sum of both. Repeated doses of pimobendan in healthy cats increased cardiac systolic function, and there were significant correlations between cardiac function and plasma concentrations of pimobendan and ODMP. The results of this study highlight the effectiveness of a higher dose of pimobendan. Full article

Oral capsule and tablet formulations of pimobendan are widely used but may present difficulties for accurately dosing small patients. This study aimed to compare the pharmacokinetic (PK) characteristics, bioequivalence, and cardiovascular effects of a custom-made oral pimobendan solution (PS) formulation compared to a reference solution (RS) formulation in conscious, healthy dogs. A randomized crossover design was performed on dogs that received RS and PS formulations at a dose of 0.3 mg/kg. Blood samples were collected at 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 24 h after oral administration for PK analysis; bioequivalence was also calculated. Echocardiography was also performed to assess the cardiovascular effects. The results revealed that the plasma concentrations of pimobendan and o-desmethyl-pimobendan (active metabolite) in the case of both formulations were comparable. The relative ratios of geometric mean concentrations for all significant parameters of PK were within a range of 80–125%, indicating bioequivalence. In addition, both formulations increased cardiac contraction significantly when compared with the baseline, and no differences in cardiac contractility were detected between the formulations. The PS formulation can be used as alternative to the RS formulation for the management of congestive heart disease because of the bioequivalence between the two formulations. Full article