RESUMEN
Patients admitted for surgical removal of varicose veins were treated in a blinded manner for 48 hours prior to surgery with either placebo, low-dose aspirin (25 mg twice daily), dipyridamole (150 mg twice daily) or both. Segments of vein excised at surgery were incubated with or without sodium arachidonate and subsequent prostacyclin (PGI2) production was measured without knowledge of treatment given. During the first 5 minute period of incubation in the presence of arachidonate, veins from dipyridamole-treated patients demonstrated increased (by 75%) arachidonate-stimulated PGI2 production compared to placebo-treated patients. By contrast, PGI2 production was reduced by 64% by aspirin treatment and 67% by aspirin plus dipyridamole compared to placebo-treated patients (p = less than 0.05). In unstimulated vein segments incubated in the absence of arachidonate, spontaneous PGI2 production during the first 5 minute incubation period was increased 32% following dipyridamole treatment but was unchanged following aspirin treatment. By contrast, unstimulated (spontaneous) PGI2 production in patients treated with aspirin plus dipyridamole was reduced by 57% (p = less than 0.05), compared to both placebo- and aspirin-treated patients, and by 71% (p = less than 0.05) compared to dipyridamole-treated patients. With repeated change of incubation medium, the ability of vein walls to produce PGI2 declined. This exhaustion was not prevented by drug treatment. However, drug effects between patient treatment groups were consistent over successive incubation periods. These results suggest that certain therapeutic benefits that might be achieved by enhancement of PGI2 production from vascular endothelium following dipyridamole treatment may be reduced by simultaneous aspirin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Aspirina/farmacología , Dipiridamol/farmacología , Epoprostenol/biosíntesis , Várices/cirugía , Aspirina/administración & dosificación , Aspirina/sangre , Dipiridamol/administración & dosificación , Dipiridamol/sangre , Método Doble Ciego , Endotelio Vascular/metabolismo , Epoprostenol/sangre , Humanos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Vena Safena/metabolismo , Tromboxano A2/biosíntesis , Tromboxano A2/sangreAsunto(s)
Infecciones Bacterianas/prevención & control , Cefoxitina/uso terapéutico , Ceftriaxona/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Premedicación , Gastropatías/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoAsunto(s)
Enfermedades Gastrointestinales/cirugía , Trastornos Nutricionales/complicaciones , Complicaciones Posoperatorias/epidemiología , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/cirugía , Factores de Riesgo , Gastropatías/cirugía , Neoplasias Gástricas/cirugíaAsunto(s)
Infecciones Bacterianas/prevención & control , Neoplasias del Colon/cirugía , Complicaciones Posoperatorias/prevención & control , Neoplasias del Recto/cirugía , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Cefotetán/administración & dosificación , Cefalosporinas/administración & dosificación , Clindamicina/administración & dosificación , Evaluación de Medicamentos , Gentamicinas/administración & dosificación , Humanos , Neomicina/administración & dosificación , Cuidados Posoperatorios , PremedicaciónAsunto(s)
Trastornos Nutricionales/complicaciones , Nutrición Parenteral Total , Neoplasias Gástricas/cirugía , Anciano , Ensayos Clínicos como Asunto , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Nutrición Parenteral Total/métodos , Cuidados Posoperatorios , Distribución AleatoriaAsunto(s)
Infecciones Bacterianas/prevención & control , Ceftriaxona/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Premedicación , Gastropatías/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Cefalosporinas/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Factores de TiempoRESUMEN
The effect of dipyridamole on prostacyclin (PGI2) production in the presence or in the absence of sodium arachidonate was examined in human veins collected from otherwise normal subjects undergoing saphenous vein removal. Vein segments, maintained in ex vivo culture, that were removed from subjects treated with dipyridamole for two days prior to surgery synthesized 2.5 times more PGI2 (p less than 0.05) than veins that were removed from placebo-treated subjects when incubated in the presence of arachidonate. This difference decreased progressively when vein segments were washed repeatedly and then re-incubated in the presence of arachidonate. Direct addition of dipyridamole to vein segments incubated in vitro resulted in a dose-dependent increase in PGI2 production when the incubation was carried out in the presence of arachidonic acid. No effect of dipyridamole was observed in experiments performed in the absence of arachidonic acid. A mathematical analysis based on both ex vivo and in vitro experiments of the rate of decline of endothelial cell PGI2 biosynthesis suggested that the elevation of PGI2 with dipyridamole treatment resulted from increased PGI2 synthesis rather than decreased PGI2 catabolism. These data support the hypothesis that dipyridamole both ex vivo and in vitro enhances and prolongs PGI2 production by human vessels.