Asunto(s)
Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Trasplante de Corazón/inmunología , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Azatioprina/uso terapéutico , Biopsia con Aguja , Creatinina/sangre , Ciclosporina/farmacocinética , Quimioterapia Combinada , Emulsiones , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Trasplante de Corazón/patología , Humanos , Inmunosupresores/farmacocinética , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Factores de TiempoAsunto(s)
Citoesqueleto/patología , Rechazo de Injerto/patología , Trasplante de Corazón/inmunología , Trasplante de Corazón/patología , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4 , Infecciones Tumorales por Virus/complicaciones , Núcleo Celular/patología , Núcleo Celular/ultraestructura , Citoesqueleto/ultraestructura , Rechazo de Injerto/inmunología , Rechazo de Injerto/virología , Corazón/virología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Linfoma/etiología , Linfoma/inmunología , Linfoma/patología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Microscopía Electrónica , Miocardio/ultraestructura , Receptores de Complemento 3d/análisis , Receptores de IgE/análisis , Receptores Virales/análisis , Vacuolas/patología , Vacuolas/ultraestructuraRESUMEN
Treatment with second generation histamine H1 receptor antagonists has been associated with lengthening of the Q-T interval and proarrhythmia. Similarly, lengthening of the Q-T interval has been reported in patients after overdosing with diphenhydramine (DPH), a first generation agent. Therefore, our study was designed 1) to assess effects of DPH on cardiac repolarization and 2) to characterize effects of the drug on major voltage-dependent cardiac K+ currents. First, we noticed that oral administration of DPH at usual dosages to healthy volunteers or to patients (prior to angioplasty) was associated with prolongation of the Q-Tc interval. Although this effect was modest in most individuals, Q-Tc was increased more than 20 ms in 7 of 20 patients. Second, we noticed that exposure of isolated guinea pig hearts to DPH 10(-5) M caused a lengthening of monophasic action potential duration. This effect was potentiated by the combined perfusion of other K+ channel blockers such as indapamide. Finally, experiments performed with the patch-clamp technique demonstrated unequivocal block of the rapid component of the delayed rectifier (IKr) by DPH; however, IC50 determined for block of IKr (3 x 10(-5) M) is approximately 40-fold greater than plasma concentrations of the drug measured at usual dosages (7 x 10(-7) M). Consequently, in agreement with the long-term clinical use of the drug, prolongation of cardiac repolarization should be minimal in most patients at usual dosages but may be observed with overdosing. Nevertheless, caution remains since excessive lengthening of cardiac repolarization may occur after administration of DPH with other drugs due to 1) concomitant block of other ionic currents or 2) pharmacokinetic interactions leading to toxic concentrations of DPH.