RESUMO
In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.
Assuntos
Coração/efeitos dos fármacos , Hidroclorotiazida/farmacologia , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Diuréticos , Relação Dose-Resposta a Droga , Eletrofisiologia , Coração/fisiologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiologia , Ventrículos do Coração/efeitos dos fármacos , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Miocárdio/citologia , Técnicas de Patch-Clamp , Canais de Potássio/efeitos dos fármacos , Ratos , Sódio/metabolismo , Estimulação QuímicaRESUMO
BACKGROUND: Reversal of ischemia after myocardial infarction by revascularization is worthwhile only if viability exists in a sufficiently large portion of the left ventricle. METHODS AND RESULTS: To determine myocardial hypoperfusion reversibility and its influence on segmental and global function, we studied 50 patients after myocardial infarction. Three technetium 99m-tetrofosmin scintigraphies were performed: 1 at rest, 1 after 0.6 mg sublingual nitroglycerin (NTG), and 1 after injection at peak stress. First-pass multigated radionuclide angiography was obtained at rest and after NTG. Each patient also underwent a stress redistribution-reinjection thallium-201 scintigraphy. During stress 99mTc-tetrofosmin, 104 segments had normal uptake, 51 showed moderately reduced uptake, and 186 had severely reduced uptake. Of these 186 segments, 33 (18%) improved at rest, and 41 (22%) improved only after NTG. Fifty-nine (79%) of these segments with improved uptake were also found to have reversible defects on 201TI imaging. In the 26 patients with ventricular dysfunction, a 73% agreement was found between the functional and 99mTc-tetrofosmin uptake post-NTG improvement, whereas a 69% agreement was found with thallium reinjection. No significant differences were seen between 99mTc-tetrofosmin and 201T1 imaging. CONCLUSION: Nitroglycerin administration during 99mTc-tetrofosmin scintigraphy improves the detection of myocardium with reversible hypoperfusion in patients with a previous myocardial infarction.
Assuntos
Circulação Coronária , Coração/diagnóstico por imagem , Nitroglicerina/farmacologia , Compostos Organofosforados , Compostos de Organotecnécio , Vasodilatadores/farmacologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Angiografia Cintilográfica , Radioisótopos de TálioRESUMO
Dynamic cardiomyoplasty improves ventricular function by increasing pump function and by limiting cardiac dilatation. The aim of this study was to assess long-term myocardial performance by radionuclide ventriculography on dilated cardiomyopathy patients subjected to cardiomyoplasty. Thirteen survivors were included. Radionuclide ventriculography was performed one week before surgery and one year later. Five patients were also studied two years following surgery. The left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and ventricular amplitude ratio (VAR) to assess mitral regurgitation were measured. Every case after one year showed a non-significant increase in LVEF. However, the decrease in EDV and in VAR was significant (p < 0.01). No significant difference in these values was found after two years. We conclude that the effects of cardiomyoplasty--reduction of cardiac dilatation, wall stress and mitral regurgitation--are more evident during the first year after surgery. Thereafter, a certain stabilization is observed.
Assuntos
Cardiomioplastia , Ventriculografia com Radionuclídeos , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Seventeen patients with effort angina, a positive exercise test and at least one stenosed vessel in coronary angiography were studied. Following a crossover blind-design, each patient received at random either 400 mg/day oral celiprolol or 120 mg/day oral nicardipine. A treadmill exercise test and 24 hour Holter monitoring were accomplished at the end of each treatment period. Both drugs significantly prolonged exercise time and reduced maximum ST segment depression at similar stages of control testing. Nicardipine reduced resting diastolic blood pressure a mean of 18 mm Hg (p less than 0.005) and also systolic blood-pressure 11 mm Hg (p less than 0.005) while celiprolol only reduced systolic pressure 10 mm Hg (p less than 0.01). Resting heart-rate was lowered by celiprolol a mean of 9 beats/min (p less than 0.0001) while nicardipine slightly increased it. The double product at maximum effort decreased with celiprolol and increased with nicardipine. Six patients with 3 vessel disease continued having transient ischemic episodes during treatment with celiprolol and 5 had them with nicardipine. Both drugs were well tolerated by the patients. In conclusion celiprolol and nicardipine proved to be effective in the treatment of myocardial ischemia specially when coronary heart disease is not very advanced.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Angina Pectoris/tratamento farmacológico , Nicardipino/uso terapêutico , Esforço Físico/efeitos dos fármacos , Propanolaminas/uso terapêutico , Angina Pectoris/diagnóstico , Celiprolol , Eletrocardiografia Ambulatorial , Teste de Esforço , HumanosRESUMO
In order to characterize postinfarction ischemia, 68 patients were studied by 24 hours Holter-monitoring and exercise testing. Twenty-four (35%) patients in Holter-monitoring and 26 (38%) in exercise testing had transient ischemic episodes. A significant coefficient of agreement was found between both tests. Nineteen (79%) of the patients had only silent ischemic episodes in Holter monitoring, and 87% of all episodes were asymptomatic. Twenty-two (87%) of the patients during positive exercise testing had silent ischemia. Eleven (46%) patients had transient ischemia at low and also at high heart-rates. Ten (37%) patients had ischemic episodes at lower charges than 100 watts, and all of them had more than 60 min of total ischemic burden in Holter-monitoring. A significant correlation was found between total ischemic burden and maximum ST segment shifts. The number of ischemic episodes were significantly higher during morning hours. A significantly higher rate of ventricular extrasystoles was found in recurrent ischemic patients, however, no difference was found in complex arrhythmias. After 1 year follow-up, 3 residual ischemic patients have died. The morbidity-calculated relative-risk is 13.9 times higher in patients with recurrent ischemia.
Assuntos
Doença das Coronárias/diagnóstico , Eletrocardiografia Ambulatorial , Eletrocardiografia , Adulto , Idoso , Complexos Cardíacos Prematuros/diagnóstico , Complexos Cardíacos Prematuros/etiologia , Doença das Coronárias/etiologia , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , RecidivaRESUMO
Hemodynamic effects of nicardipine (60 mg) were evaluated in 20 patients whose left ventricular ejection fraction was less than 55%. Nicardipine significantly reduced the mean arterial blood pressure by 28 mmHg (p less than 0.0005). Left ventricular ejection fraction and maximal rate of ventricular diastolic filling were increased in 12% and 84.0 VDF/s (p less than 0.0005) respectively. The end diastolic volume was reduced by 26 ml (p less than 0.001). The decrease in mean arterial blood pressure correlates with the increase in the left ventricular ejection fraction (r = 0.76, p less than 0.001) as well as with the reduced end diastolic volume (R = 0.43, p less than 0.05). The results obtained corroborate the beneficial effects of nicardipine on ventricular function of ischemic patients, whose cardiac reserve is reduced.
Assuntos
Doença das Coronárias/fisiopatologia , Nicardipino/farmacologia , Administração Oral , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Humanos , Nicardipino/administração & dosagem , Ventriculografia com Radionuclídeos/métodos , Volume Sistólico/efeitos dos fármacosRESUMO
The effects of oral verapamil monotherapy (320 mg/day) given to a group of essential hypertensive patients (n = 16) on blood pressure, electrocardiogram (ECG) and ventricular function measured by means of nuclear ventriculography (NV) were investigated. Verapamil significantly lowered systolic (SP) (p less than 0.001) and diastolic (DP) (p less than 0.001) blood pressure. Left ventricular ejection fraction (LVEF) and ejection rate (LVER) were reduced from 61.61 +/- 6.34 to 54.16 +/- 6.09% (p less than 0.001) and from 255.6 +/- 58.9 to 217.4 +/- 56.03% (p less than 0.02), respectively. On the other hand, in the right ventricle, the drug only reduced the right ventricular filling rate (RVFR) from 225.2 +/- 60.02 to 167.5 +/- 43.7% (p less than 0.05). Total blood volume (TBV) was also significantly diminished (p less than 0.05). Variations in LVEF (delta LVEF) and RVEF (delta RVEF) correlated with variations in blood pressures and TVB (delta TVB). The results indicate that the hypotensive action mechanism of verapamil could be explained at least in part by a reduction in LVEF and systemic vasodilatation.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Eletrocardiografia/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Verapamil/uso terapêutico , Administração Oral , Adulto , Feminino , Ventrículos do Coração/efeitos dos fármacos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Ventriculografia com Radionuclídeos , Função Ventricular , Verapamil/administração & dosagemRESUMO
Twenty-seven hypertensive outpatients were studied to evaluate the efficacy of verapamil after a single oral dose as well as following a short-term treatment and also in combination with oxprenolol. Blood pressure was significantly reduced (p 0.01) after verapamil monotherapy and the combined treatment. PR interval was lengthened from 30 min to 4 h during acute testing, and also after short-term treatment. QT was only prolonged after the verapamil monotherapy. Systolic time intervals (STIs) were not modified, except left ventricular ejection time (LVETc). Direct correlations were found among verapamil plasma concentrations and changes provoked on blood pressure and PR interval. The mean side effects found were disturbance of atrioventricular conduction in two patients without ulterior complications. The results suggest that verapamil monotherapy or in combination with oxprenolol could be useful in the treatment of essential hypertension.
Assuntos
Hipertensão/tratamento farmacológico , Verapamil/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Avaliação de Medicamentos , Quimioterapia Combinada , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Oxprenolol/administração & dosagem , Estatística como Assunto , Verapamil/administração & dosagem , Verapamil/sangueRESUMO
Las tecnicas nucleares que emplean camara gamma y computadora digital, han cobrado especial interes en cardiologia durante los ultimos anos.Estos procedimientos presentan como principales ventajas su simplicidad y caracter no invasivo, asi como la informacion que permiten disponer.En el trabajo se presenta la tecnica de ventriculografia nuclear empleada en el laboratorio de los autores y los resultados obtenidos en un grupo de sujetos normales y pacientes con cardiopatia isquemica. Los parametros que se calculan son: fracciones de ejeccion y velocidades de llenado y vaciamiento para cada ventriculo. Ademas se determina el retardo de la contraccion de un ventriculo respecto al otro. El movimiento de paredes se estudia por medio de las imagenes de fase y amplitud, obtenidas al aplicar el aparato matematico de la transformada de Fourier a la ventriculografia nuclear. Estas imagenes diferencian zonas normokineticas de aquinesias e hipoquinesias regionales y permiten identificar segmentos con movimiento paradojico.Los resultados obtenidos con la ventriculografia izquierda y coronariografia en 15 sujetos. Se concluye en la utilidad y valor de la ventriculografia nuclear en una serie de situaciones clinicas
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Doença das Coronárias , Cintilografia , Ventrículos do CoraçãoAssuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Infarto do Miocárdio , CintilografiaAssuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Cintilografia , Infarto do MiocárdioRESUMO
Twenty patients with coronary heart disease subjected to exercise testing presented ventricular arrhythmias. In a "double blind" design, oral disopyramide was administered during 7 days, after which the test was repeated. In 16 patients disopyramide prevented the appearance of arrhythmia or decreased their severity. Basal heart rate increased. Significant toxic or colateral effects were not observed. In 6 cases, placebo also hindered exercise arrhythmias. It is suggested that disopyramide may be useful in the prevention of sudden death from ventricular arrhythmias.