Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Curr Med Chem ; 21(11): 1271-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23992336

RESUMO

Ranolazine has primarily been developed and so far approved as an antianginal drug. However, it also has potentially interesting and relevant antiarrhythmic properties. Its antiarrhythmic effects are mainly based on the blockade of sodium currents, in particular of the late sodium current. Experimental and clinical studies have revealed an antiarrhythmic effect of ranolazine in atrial fibrillation as chronic or "pill in the pocket" therapy. Of note, this effect was preserved in the setting of chronic heart failure. Furthermore, an antiarrhythmic effect has also been shown in experimental models of ventricular tachyarrhythmias. In addition, prevention of ventricular tachyarrhythmias has been demonstrated in patients with structural heart disease. A few late sodium current inhibitors are evaluated for antiarrhythmic properties in experimental studies. However, randomized clinical data is not yet available for these recently developed agents and larger controlled trials are necessary before recommending ranozaline as a novel antiarrhythmic drug.


Assuntos
Antiarrítmicos/uso terapêutico , Fenômenos Eletrofisiológicos , Sódio/química , Antiarrítmicos/química , Arritmias Cardíacas/tratamento farmacológico , Fibrilação Atrial/tratamento farmacológico , Combinação de Medicamentos , Humanos , Sódio/metabolismo
2.
Int J Cardiol ; 169(5): 366-70, 2013 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-24182908

RESUMO

INTRODUCTION: Catheter ablation for idiopathic ventricular arrhythmia is well established but epicardial origin, proximity to coronary arteries, and limited accessibility may complicate ablation from the venous system in particular from the great cardiac vein (GCV). METHODS: Between April 2009 and October 2010 14 patients (56 ± 15 years; 9 male) out of a total group of 117 patients with idiopathic outflow tract tachycardias were included undergoing ablation for idiopathic VT or premature ventricular contractions (PVC) originating from GCV. All patients in whom the PVC arose from the GCV were subject to the study. In these patients angiography of the left coronary system was performed with the ablation catheter at the site of earliest activation. RESULTS: Successful ablation was performed in 6/14 (43%) and long-term success was achieved in 5/14 (36%) patients. In 4/14 patients (28.6%) ablation was not performed. In another 4 patients (26.7%), ablation did not abolish the PVC/VT. In the majority, the anatomical proximity to the left coronary system prohibited effective RF application. In 3 patients RF application resulted in a coronary spasm with complete regression as revealed in repeat coronary angiography. CONCLUSION: A relevant proportion idiopathic VT/PVC can safely be ablated from the GCV without significant permanent coronary artery stenosis after RF application. Our data furthermore demonstrate that damage to the coronary artery system is likely to be transient.


Assuntos
Ablação por Cateter/métodos , Vasos Coronários , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/cirurgia , Complexos Ventriculares Prematuros/diagnóstico por imagem , Complexos Ventriculares Prematuros/cirurgia , Adulto , Idoso , Ablação por Cateter/efeitos adversos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Fatores de Risco , Resultado do Tratamento
3.
Br J Pharmacol ; 166(2): 557-68, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22013922

RESUMO

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca(2+) overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether I(Ca) blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K(+) ] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block I(Kr) in CHF hearts. After lowering [K(+) ] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of I(Ca) . CONCLUSIONS AND IMPLICATIONS Blockade of I(Ca) was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01818.x.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Taquicardia Ventricular/tratamento farmacológico , Verapamil/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Eritromicina/farmacologia , Feminino , Coração/efeitos dos fármacos , Coração/fisiologia , Insuficiência Cardíaca/fisiopatologia , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Bloqueadores dos Canais de Potássio/farmacologia , Coelhos , Taquicardia Ventricular/fisiopatologia , Verapamil/farmacologia
4.
Dtsch Med Wochenschr ; 133 Suppl 8: S285-9, 2008 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-19085808

RESUMO

One major cause of sudden cardiac death in heart failure is the occurrence of life-threatening polymorphic ventricular tachycardia. Especially in the early stages of heart failure half of the deaths are sudden and unexpected. The majority of these are caused by ventricular tachyarrhythmias. Whereas reentry plays a major role in patients after myocardial infarction, triggered activity is responsible for the occurrence of arrhythmic events in non-ischemic heart failure. Action potential prolongation serves as the electrophysiological basis for the formation of triggered activity and the underlying early afterdepolarizations. It has been demonstrated in heart failure and in cardiac hypertrophy that this results from a reduction in outward repolarizing ion currents, especially due to downregulation of potassium channels. The underlying substrate for the maintenance of arrhythmias in chronic heart failure in experimental models and in humans is an increase in dispersion of repolarization. It opens the floodgate to the occurrence of potentially life-threatening polymorphic ventricular arrhythmias and leads to their maintenance. Thus chronic heart failure leads to a reduced repolarization reserve, i.e. a patient-specific response to risk factors that influence repolarization. Additional risk factors in patients with heart failure are hypokalemia (diuretic therapy), bradycardia (AV block) or concomitant therapy with repolarization prolonging drugs (antiarrhythmic drugs, antibiotics etc.) that may add further stress on the repolarization process and set the stage for the occurrence of life-threatening arrhythmias. One promising therapeutic approach to suppress arrhythmias in chronic heart failure may be a selective blocking of the Na+/Ca2+ exchanger. Experimental data have recently demonstrated a reduction of action potential duration, and dispersion of repolarization as well as suppression of early afterdepolarizations and torsade de pointes in an isolated intact heart model of chronic heart failure in a proarrhythmic milieu due to block of the Na+/Ca2+ exchanger.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomegalia/complicações , Insuficiência Cardíaca/complicações , Potenciais de Ação , Animais , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Cardiomegalia/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Fatores de Risco , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/metabolismo , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologia , Torsades de Pointes/etiologia , Torsades de Pointes/mortalidade , Torsades de Pointes/fisiopatologia
5.
Basic Res Cardiol ; 100(4): 365-71, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15944809

RESUMO

BACKGROUND: In long QT syndrome (LQTS), prolongation of the QT-interval is associated with sudden cardiac death resulting from potentially life-threatening polymorphic tachycardia of the torsade de pointes (TdP) type. Experimental as well as clinical reports support the hypothesis that calcium channel blockers such as verapamil may be an appropriate therapeutic approach in LQTS. We investigated the electrophysiologic mechanism by which verapamil suppresses TdP, in a recently developed intact heart model of LQT3. METHODS AND RESULTS: In 8 Langendorff-perfused rabbit hearts, veratridine (0.1 microM), an inhibitor of sodium channel inactivation, led to a marked increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p < 0.05) thereby mimicking LQT3. In bradycardic (AV-blocked) hearts, simultaneous recording of up to eight epi- and endocardial MAPs demonstrated a significant increase in total dispersion of repolarization (56%, p < 0.05) and reverse frequency-dependence. After lowering potassium concentration, veratridine reproducibly led to early afterdepolarizations (EADs) and TdP in 6 of 8 (75%) hearts. Additional infusion of verapamil (0.75 microM) suppressed EADs and consecutively TdP in all hearts. Verapamil significantly shortened endocardial but not epicardial MAPs which resulted in significant reduction of ventricular transmural dispersion of repolarization. CONCLUSIONS: Verapamil is highly effective in preventing TdP via shortening of endocardial MAPs, reduction of left ventricular transmural dispersion of repolarization and suppression of EADs in an intact heart model of LQT3. These data suggest a possible therapeutic role of verapamil in the treatment of LQT3 patients.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Síndrome do QT Longo/tratamento farmacológico , Torsades de Pointes/prevenção & controle , Verapamil/farmacologia , Animais , Cálcio/metabolismo , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/fisiopatologia , Masculino , Coelhos , Verapamil/uso terapêutico
6.
Ann Plast Surg ; 4(5): 426-9, 1980 May.
Artigo em Inglês | MEDLINE | ID: mdl-7436273

RESUMO

A case of giant cell tumor compression of the ulnar nerve at the loge de Guyon is noted. Due to great variation of the anatomy of the deep branch, plus the varying locations of lesion appearance, numerous presentations of the ulnar tunnel syndrome are manifested. When recognized, early surgery and complete decompression are in order.


Assuntos
Tumores de Células Gigantes/complicações , Síndromes de Compressão Nervosa/etiologia , Tendões/cirurgia , Nervo Ulnar/cirurgia , Adulto , Tumores de Células Gigantes/patologia , Tumores de Células Gigantes/cirurgia , Humanos , Masculino , Síndromes de Compressão Nervosa/cirurgia
7.
Ann Bot ; 90(6): 707-14, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12451026

RESUMO

The role of dormancy, temperature and light in the regulation of seed germination of four annual Asteraceae from south-western Australia was investigated. The experiments aimed to identify after-ripening patterns, and to relate these to climatic conditions of the habitat in which the species occur. Seeds of all species were strongly dormant at maturity and maintained high levels of dormancy for time periods corresponding to the duration of summer in south-western Australia. Dry after-ripening was promoted best by temperatures lower than those prevailing in the dry season, although differences among storage temperatures were mostly insignificant. Germination percentages were highest at average winter temperatures (15 degrees C). A logistic model revealed significant differences in germinability among species, but not between incubation temperatures or light and dark treatments across species. Three species with seeds >0.5 mg germinated better in darkness than in light, whereas germination in darkness was almost inhibited in the species with the smallest seeds (0.14 mg). The course of dormancy loss, tested over a range of fluctuating incubation temperatures (7-30 degrees C), showed that seeds of three species came out of dormancy first at temperatures that prevail in south-western Australia during the winter (10-15 degrees C). Seeds from one species, introduced from South Africa, first lost dormancy at the lowest temperature (7 degrees C). All species showed after-ripening patterns of Type 1, typical of species growing in Mediterranean climates. The germination characteristics of the investigated species can be interpreted as ensuring that initial growth and establishment occur during the winter growing season, thereby avoiding the hot and dry summer conditions that follow seed dispersal.


Assuntos
Asteraceae/fisiologia , Sementes/fisiologia , Asteraceae/classificação , Asteraceae/efeitos da radiação , Austrália , Escuridão , Germinação/fisiologia , Germinação/efeitos da radiação , Luz , Sementes/crescimento & desenvolvimento , Sementes/efeitos da radiação , Especificidade da Espécie , Temperatura
8.
Eur Heart J ; 23(17): 1394-401, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12191751

RESUMO

INTRODUCTION: Numerous reports on the inducibility of ventricular tachyarrhythmias (VT) in patients with atypical right bundle branch block and right precordial ST-elevation (Brugada syndrome) are based on multicentre studies that have used different stimulation protocols. Therefore, we prospectively investigated the inducibility of VT in these patients using a uniform protocol. METHODS: In 41 consecutive patients (29 males) showing a pattern of right bundle branch block and ST-elevation, programmed ventricular stimulation was performed in the right ventricular apex with up to three premature stimuli at sinus rhythm and at four different paced cycle lengths (500, 430, 370, and 330 ms) until refractoriness was reached or reproducible induction of a sustained (>30s) VT occurred. If a VT was not reproducibly inducible, the same protocol was repeated in the right ventricular outflow tract. RESULTS: A history of life-threatening events defined as syncope (n=17) or aborted sudden cardiac death (n=13) was present in 30 patients (73%); 11 individuals were asymptomatic. Inducibility (68%) was similar between symptomatic (n=21, 70%) and asymptomatic patients (n=7, 64%). In 16 (39%) patients, VT were reproducibly inducible. If patients were only stimulated in the right ventricular apex, inducibility rate decreased to 39%. If only two premature beats at two sites were used it was as low as 32%. The mean coupling intervals of the second and third premature stimuli inducing sustained VT were short: 189+/-21 ms vs 186+/-22 ms, respectively. Forty-four percent of all patients (i.e. 64% of the inducible patients) had inducible VT only with coupling intervals shorter than 200 ms. CONCLUSIONS: The stimulation protocol markedly influences the extent of inducibility of VT in patients with right bundle branch block and ST-segment elevation. These findings question the significance of previous multicentre studies using different stimulation protocols and should have implications for further studies.


Assuntos
Bloqueio de Ramo/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Adulto , Idoso , Desfibriladores Implantáveis , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome , Fibrilação Ventricular/fisiopatologia
9.
J Hand Surg Am ; 7(4): 424, 1982 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7119404
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA