RESUMEN
This study was designed to determine the hemodynamic effects of the class III antiarrhythmic agent d-sotalol in acute ischemic heart failure at concentrations that prolong ventricular repolarization. In pentobarbital-anesthetized open-chest dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular (LV) end-diastolic pressure of 25 +/- 2 mm Hg was achieved. Embolization shortened the QT interval by 30 +/- 11 msec, while 1 and 2 mg/kg d-sotalol intravenously after embolization lengthened the QT interval by 23 +/- 7 and 39 +/- 7 msec, respectively (n = 7). Heart rate increased after embolization by 19 +/- 7 beats/min, while it decreased by 12 +/- 6 beats/min and by 21 +/- 5 beats/min after d-sotalol. The depressed LV function after embolization assessed by LV pressures, stroke volume, cardiac output, ultrasonometrically estimated LV volume, the pressure-volume relationship, and the time for isovolumic relaxation was not changed following infusion of 1 or 2 mg/kg d-sotalol. Plasma concentrations of d-sotalol were 1.55 +/- 0.33 and 2.58 +/- 0.50 micrograms/ml, respectively. In conclusion, d-sotalol at concentrations prolonging repolarization was devoid of cardiodepressive effects in acute ischemic heart failure in dogs.
Asunto(s)
Enfermedad Coronaria/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Sotalol/uso terapéutico , Enfermedad Aguda , Animales , Enfermedad Coronaria/sangre , Enfermedad Coronaria/fisiopatología , Diástole/efectos de los fármacos , Diástole/fisiología , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/fisiología , Masculino , Sotalol/sangre , Sístole/efectos de los fármacos , Sístole/fisiologíaRESUMEN
Earlier studies have shown that selenium and vitamin E are important in maintaining normal cardiac function. The present study was designed to test the effect of sole selenium deficiency on electrophysiological and mechanical characteristics of the rat heart. Male weanling rats were fed a standardized vitamin E adequate but selenium deficient diet, or a control diet. Deficiency of selenium was verified by direct (tissue selenium analyses) and indirect (glutathione-peroxidase tissue analyses) methods. In vivo electrocardiographic recordings as well as in vitro electrophysiological and mechanical recordings did not reveal abnormalities in any of the two groups. In conclusion, earlier studies have shown that the combined deficiency of selenium and vitamin E leads to abnormal cardiac function. Selenium deficiency alone, however, does not appear to significantly affect cardiac function in the rat.