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1.
J Vet Cardiol ; 41: 179-193, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35366640

RESUMO

INTRODUCTION: Heart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality. OBJECTIVES: To investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP. ANIMALS: Three hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned. METHODS: Prospective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity. RESULTS: Median time to primary outcome was 84 days (95% confidence interval [CI]: 63-219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145-377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG. CONCLUSIONS: Heart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.


Assuntos
Cardiomiopatias , Doenças do Gato , Insuficiência Cardíaca , Animais , Gatos , Benzazepinas , Cardiomiopatias/complicações , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/veterinária , Doenças do Gato/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/veterinária , Piperidinas , Estudos Prospectivos
2.
Schweiz Arch Tierheilkd ; 155(2): 143-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23385073

RESUMO

In this article the myocardial expression of different hyperpolarization-activated, cyclic nucleotide-gated (HCN) isoforms in myocardial tissue from healthy control cats and cats with hypertrophic cardiomyopathy (HCM) was evaluated. Myocardial tissue samples of the left ventricle of control cats (n = 12) and cats with HCM (n = 4) were collected. Expression of feline HCN was determined by immunoblot analysis using antibodies against HCN2 and HCN4. Optical densities of HCN bands were compared among groups by use of the Mann-Whitney Rank Sum test. HCN4 was reliably detected in myocardial tissue whereas HCN2 was not. HCN4 expression was significantly increased in left ventricular (LV) myocardial samples of cats with HCM (P = 0.036) compared to control cats. Results indicate that myocardial HCN4 expression can be evaluated in cats by immunoblot analysis and that HCN4 expression is upregulated in LV myocardial tissue of cats with HCM. The pathophysiological importance of HCN overexpression with regard to myocyte function and altered automaticity deserves further study.


Assuntos
Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Miocárdio/metabolismo , Animais , Anticorpos/imunologia , Especificidade de Anticorpos , Western Blotting/veterinária , Cardiomiopatia Hipertrófica/metabolismo , Estudos de Casos e Controles , Gatos , Ventrículos do Coração , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/imunologia
3.
J Vet Intern Med ; 25(3): 469-76, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21418320

RESUMO

BACKGROUND: Ivabradine is a novel negative chronotropic drug used for treatment of ischemic heart disease in people. Little is known about its effects and safety in cats. HYPOTHESIS/OBJECTIVES: Ivabradine is not inferior to atenolol with regard to clinical tolerance, heart rate (HR) reduction, and effects on cardiac function in healthy, lightly sedated cats. ANIMALS: Ten healthy laboratory cats. METHODS: Physical examination, systolic blood pressure measurement, and transthoracic echocardiography were performed in all cats at baseline and after oral administration (4 weeks each) of ivabradine (0.3 mg/kg q12h) and atenolol (6.25 mg/cat q12h; 1.0-1.7 mg/kg) in a prospective, double-blind, randomized, active-control, fully crossed study. A priori noninferiority margins for the effects of ivabradine compared with atenolol were set at 50% (f = 0.5) based on predicted clinical relevance, observer measurement variability, and in agreement with FDA guidelines. Variables were compared by use of 2-way repeated measures ANOVA. RESULTS: Ivabradine was clinically well tolerated with no adverse events observed. HR (ivabradine, P < .001; atenolol, P < .001; ivabradine versus atenolol, P = .721) and rate-pressure product (RPP) (ivabradine, P < .001; atenolol, P = .001; ivabradine versus atenolol, P = .847) were not different between treatments. At the dosages used, ivabradine demonstrated more favorable effects than atenolol on echocardiographic indices of left ventricular (LV) systolic and diastolic function and left atrial performance. CONCLUSIONS AND CLINICAL IMPORTANCE: Ivabradine is not inferior to atenolol with regard to effects on HR, RPP, LV function, left atrial performance, and clinical tolerance. Clinical studies in cats with hypertrophic cardiomyopathy are needed to validate these findings.


Assuntos
Atenolol/farmacologia , Benzazepinas/farmacologia , Gatos/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Antiarrítmicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Cardiotônicos/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Ivabradina
4.
J Vet Pharmacol Ther ; 34(5): 469-75, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21118419

RESUMO

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method for the measurement of the novel heart rate-lowering drug ivabradine and its major metabolite, S-18982, was cross-validated in the plasma of eight healthy cats. Plasma concentrations were then determined after single and repeated oral administration of ivabradine. Individual plasma concentrations versus time from each cat were used in compartmental analysis using the commercially available software WinNonlin. Both ivabradine and S-18982 reached their maximum concentrations of 103.33 and 3.86 ng/mL within 1 h. Following repeated administration, areas under the plasma concentration-time curves for ivabradine and S-18982 did not significantly increase. Two-compartmental and one-compartmental models with first-order input and elimination provided the best fit to the data for ivabradine and S-18982, respectively. Both models were combined to produce a single 4-compartment model characterizing ivabradine and S-18982 pharmacokinetics. The results of this study indicate that repeated oral doses of ivabradine produced plasma drug concentrations suitable for 12-h dosing intervals in healthy cats. Furthermore, the analytical assay and combined ivabradine/S-18982 model provide tools for further evaluation of ivabradine pharmacokinetics and pharmacodynamics in future studies in cats.


Assuntos
Benzazepinas/administração & dosagem , Benzazepinas/farmacocinética , Administração Oral , Animais , Benzazepinas/sangue , Benzazepinas/metabolismo , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/sangue , Fármacos Cardiovasculares/metabolismo , Fármacos Cardiovasculares/farmacocinética , Doenças do Gato , Gatos , Cromatografia Líquida/métodos , Cromatografia Líquida/veterinária , Feminino , Ivabradina , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/veterinária
6.
Schweiz Arch Tierheilkd ; 149(2): 65-71, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17343132

RESUMO

A total of 408 cats with various cardiovascular problems has been presented to two investigational clinics during the last 8 years. The number of yearly examinations has steadily increased during this period. Definitive cardiovascular disease was diagnosed in 287 cats, whereby hypertrophic cardiomyopathy (HCM) was the most common diagnosis with 67.6%. Congenital cardiovascular malformations were found in 11.8% of the cases. Ventricular septal defect (VSD) was the most frequent anomaly, in contrast to previously published studies. The ECG was found to be relatively non-specific and insensitive for the diagnosis of heart disease: Its usefulness lies in the recognition and diagnosis of cardiac arrhythmias. The radiographically recognized changes were also non-specific for certain heart diseases. Radiographs of the thorax are especially useful in the evaluation of cardiomegaly, and secondary signs of congestion.


Assuntos
Doenças do Gato/diagnóstico , Doenças do Gato/epidemiologia , Cardiopatias/veterinária , Animais , Gatos , Diagnóstico Diferencial , Ecocardiografia/métodos , Ecocardiografia/veterinária , Eletrocardiografia/métodos , Eletrocardiografia/veterinária , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/veterinária , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Masculino , Miocárdio/patologia , Prevalência , Radiografia Torácica/métodos , Radiografia Torácica/veterinária , Suíça/epidemiologia
7.
Schweiz Arch Tierheilkd ; 149(2): 73-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17343133

RESUMO

During the last 3 years, a total of 144 cats underwent echocardiographic screening at two investigational clinics before being admitted for breeding. The number of cats presented for that purpose has constantly increased. 8.3% of cats were diagnosed as having hypertrophic cardiomyopathy and 6.9% were diagnosed as suspicious. Male cats were more affected than females (9.4% vs 7.7%). In 4.2 of all presented cats, a congenital cardiac malformation was recognised, most often tricuspid valve dysplasia.


Assuntos
Cruzamento , Doenças do Gato/diagnóstico , Ecocardiografia/veterinária , Cardiopatias Congênitas/veterinária , Programas de Rastreamento/veterinária , Animais , Doenças do Gato/epidemiologia , Gatos , Ecocardiografia/métodos , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Masculino , Programas de Rastreamento/métodos , Estudos Retrospectivos , Fatores Sexuais
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