RESUMEN
Myocardial deterioration is relentlessly progressive in almost all patients who develop overt symptoms. Many dilated cardiomyopathies are associated with a marked increase in cardiac sympathetic tone which may be toxic to myocytes. Microvascular spasm, leading to diffuse, focal reperfusion injury, also appears to be an important mechanism of cardiomyocyte loss in many models of dilated cardiomyopathy. Free radicals may mediate both catecholamine-induced damage and reperfusion injury. We hypothesized that myocardial antioxidant reserve may be significantly reduced in dilated cardiomyopathy and that alpha-tocopheryl acetate may be of benefit. The enzymes superoxide dismutase, catalase and glutathione peroxidase were measured in the myocardial tissue of control and cardiomyopathic hamsters in early (25-50 days) and late (275-320 days) stages of the cardiomyopathy. In another study, myocardial glutathione peroxidase activity and protein oxidation was measured in control and late stage cardiomyopathic hamsters receiving alpha-tocopheryl (70 mg/kg/day) or vehicle for 1 month. There were no significant differences in glutathione peroxidase activity between control and cardiomyopathic hamsters in the early stage of the cardiomyopathy. Superoxide dismutase and catalase activities did not change with aging; however, glutathione peroxidase decreased over 30%, alpha-tocopherol was reduced by approximately 50% and protein oxidation increased more than 2-fold in the hearts of late stage cardiomyopathic hamsters. Alpha-tocopheryl acetate administration restored alpha-tocopherol levels, glutathione peroxidase activity and protein oxidation to normal. We conclude that the decompensating heart has significantly limited antioxidant reserve and that this reserve is sensitive to the intake of antioxidant supplements.
Asunto(s)
Cardiomiopatía Dilatada/metabolismo , Estrés Oxidativo , Vitamina E/análogos & derivados , Vitamina E/metabolismo , alfa-Tocoferol/análogos & derivados , Animales , Cardiomiopatía Dilatada/tratamiento farmacológico , Catalasa/metabolismo , Cricetinae , Glutatión Peroxidasa/metabolismo , Masculino , Mesocricetus , Miocardio/metabolismo , Oxidación-Reducción , Proteínas/metabolismo , Superóxido Dismutasa/metabolismo , Tocoferoles , Vitamina E/uso terapéuticoAsunto(s)
Infarto Cerebral/prevención & control , Demencia por Múltiples Infartos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Embolia y Trombosis Intracraneal/tratamiento farmacológico , Medicina Tradicional China , Aspirina/uso terapéutico , Quimioterapia Combinada , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
To determine the effect of vitamin E on cellular antioxidant enzymes, human ventricular cardiomyocytes were incubated with 200 microM all-racemic-alpha-tocopheryl acetate for 14 d at pO2s of 150 and 40 mm Hg. Cellular Cu, Zn superoxide dismutase, catalase, and GSH-Px1 activities were measured. Although SOD and catalase activities were unaffected by alpha-tocopherol, GSH-Px1 activities increased (p < .0001) as much as twofold. This increase was independent of oxygen tension and selenium. The increase in GSH-Px1 activity became significant (p < .01) by day 4. A nonantioxidant analog of alpha-tocopherol, 200 microM RRR-alpha-tocopherol methyl ether, did not affect GSH-Px1 activities. Although GSH-Px1 mRNA levels mirrored the changes in enzyme activities, the de novo nuclear GSH-Px1 transcript synthesis was unaffected by alpha-tocopherol. Because the increase in GSH-Px1 activities also occurred after cellular alpha-tocopherol levels had plateaued, the above results were most consistent with posttranscriptional stabilization of GSH-Px1 mRNA by alpha-tocopherol or an alpha-tocopherol-related metabolic product.
Asunto(s)
Antioxidantes/farmacología , Glutatión Peroxidasa/biosíntesis , Miocardio/enzimología , Transcripción Genética/efectos de los fármacos , Vitamina E/análogos & derivados , alfa-Tocoferol/análogos & derivados , Análisis de Varianza , Catalasa/metabolismo , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Medios de Cultivo , Glutatión Peroxidasa/metabolismo , Ventrículos Cardíacos , Humanos , Cinética , Oxígeno/análisis , ARN Mensajero/biosíntesis , Selenio/farmacología , Superóxido Dismutasa/metabolismo , Factores de Tiempo , Tocoferoles , Vitamina E/farmacologíaRESUMEN
Both Trolox (a water-soluble analogue of alpha-tocopherol) and ascorbic acid were more effective than superoxide dismutase or catalase in protecting myocyte cell cultures from free radical attack (induced by hypoxanthine and xanthine oxidase). In a canine model of two hours of left anterior descending coronary artery occlusion followed by four hours of reperfusion, Trolox and ascorbic acid reduced the area of infarction within the area at risk. The Trolox group received 500 mL of deoxygenated saline solution containing 2.0 g of Trolox, 3.0 g of ascorbic acid, and 18 mg of EDTA (ethylenediaminetetraacetic acid) infused into the ascending aorta 30 seconds before and four minutes after reperfusion. Saline controls received 500 mL of deoxygenated saline solution containing 18 mg of EDTA. The angioplasty group had unmodified reperfusion by simple release of the occlusion. The area at risk and the area infarcted were estimated with Evans blue and triphenyl tetrazolium hydrochloride stains, respectively. The ratio of the area infarcted to the area at risk was significantly lower with Trolox (angioplasty, 30.4% +/- 5.1%; saline, 20.8% +/- 2.9%; and Trolox, 8.7% +/- 4.0%; p less than 0.01). In summary, the antioxidants Trolox and ascorbic acid effectively reduced myocardial necrosis after ischemia.