RESUMEN
Using the blood-bathed technique of Vane we induced acute coronary occlusion in the dog and subsequently detected adrenaline release into the circulatory system, determined the rate of release and documented its significance for induction of cardiac arrhythmias. In the intact anesthetized dog, adrenaline excess of the magnitude released after coronary occlusion was sufficient to injure the healthy myocardium and to induce unfavorable metabolic systemic alterations. Subsequently, clinical research has documented that a serious clinical course of acute myocardial infarction is associated not only with enhanced excretion of catecholamines but also with augmentation of plasma renin activity and aldosterone levels. The positive therapeutic effect of aldosterone antagonists in acute myocardial infarction has been documented. The clinical value of our results, which were obtained in experimental and clinical studies, was later confirmed in multi-center trials.
Asunto(s)
Arritmias Cardíacas/metabolismo , Epinefrina/metabolismo , Infarto del Miocardio/metabolismo , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Receptores Adrenérgicos/metabolismo , Animales , Catecolaminas/sangre , Perros , Epinefrina/sangre , Corazón/inervación , Sistema de Conducción Cardíaco/fisiopatología , Infarto del Miocardio/fisiopatología , Ratas , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
BACKGROUND: There is significant evidence that reactive oxygen species play an important role in endothelial dysfunction, ischemia/reperfusion injury as well as in the pathogenesis of diabetes mellitus (DM). It is also known that vitamins C and E have substantial antioxidant properties. However, clinical evidence concerning this topic is insufficient so far. The aim of the present study was to determine if the administration of vitamins C and E influences the outcome in diabetic patients with acute myocardial infarction (AMI). METHODS: Among 800 patients with AMI included in the MIVIT (Myocardial Infarction and Vitamins) study, 122 patients (15%) had confirmed DM. A retrospective analysis of the influence of vitamins C and E on 30-day cardiac mortality in patients with or without DM was performed. RESULTS: There was a significant reduction in 30-day cardiac mortality in diabetic patients treated with antioxidant vitamins C and E [5 (8%) vs. 14 (22%); OR 0.32, 95% CI 0.11-0.93; p = 0.036]. Such an effect has not been observed in patients without DM [19 (6%) vs. 19 (6%); OR 0.97, 95% CI 0.51-1.85; p = 0.94]. CONCLUSION: The results suggest that early administration of antioxidant vitamins C and E in patients with AMI and concomitant DM reduces cardiac mortality.
Asunto(s)
Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Diabetes Mellitus/mortalidad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Vitamina E/administración & dosificación , Anciano , Diabetes Mellitus/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proyectos Piloto , Ensayos Clínicos Controlados Aleatorios como Asunto , Especies Reactivas de Oxígeno/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIMS: In patients with acute myocardial infarction (MI), low serum triiodothyronine (T3) concentration is commonly associated with a severe clinical course. The aim of this prospective study was to investigate whether a severe clinical course in patients with low T3 is related to the magnitude of myocardial injury assessed by echocardiography. METHODS AND RESULTS: Out of 635 patients with MI we enrolled 100 consecutive patients. They were divided in two subgroups: group A, 81 patients without clinical hard events (death, resuscitation following ventricular tachycardia/vertricular fibrillation, new MI) and group B, 19 patients in whom at least one of the above hard events occurred during hospital stay. Thyroid function tests were performed on day 1, 4 and 7, echocardiographic examinations measuring asynergic area (AA), and wall motion score index (WMSI) between day 1 and 5 (median 3). A negative correlation was found between plasma free triiodothyronine (FT3), concentration and AA (p<0.001), FT3 and WMSI (p<0.001) values at all time points. FT3 concentration was lower in group B than group A at all time points (p<0.001). CONCLUSIONS: In patients with acute MI, low FT3 state is related to the extent of myocardial damage.
Asunto(s)
Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Glándula Tiroides/fisiopatología , Triyodotironina/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In congestive heart failure (CHF), endothelial dysfunction may contribute to impairment of exercise induced vasodilatation and decreased exercise capacity. We hypothesised that administration of L-arginine, a precursor of nitric oxide (NO) and postulated antioxidant, may improve endothelium-dependent vasodilatation and exercise capacity and also exert antioxidant activity. AIMS: To investigate the effect of oral supplementation with L-arginine on exercise capacity and markers of oxidative stress in patients with mild to moderate CHF. METHODS: The study had a randomised double-blind cross-over design. Twenty one patients with stable NYHA II-III CHF underwent three exercise tests: initially, after oral administration of L-arginine (9 g/day for 7 days) or placebo. Blood was sampled prior to each test for plasma lipid peroxides, reduced sulphydryl groups and leukocyte oxygen free radical production. RESULTS: We found a higher prolongation of exercise duration time after L-arginine than after placebo (99+/-106 vs 70+/-99 s, p<0.05). There were no significant differences in markers of free radical activity. CONCLUSIONS: In patients with chronic stable CHF, oral supplementation with L-arginine prolongs exercise duration which may be due to NO-induced peripheral vasodilatation. The antioxidant properties of L-arginine have not been confirmed in this ex vivo study.
Asunto(s)
Arginina/farmacología , Suplementos Dietéticos , Endotelio Vascular/efectos de los fármacos , Tolerancia al Ejercicio/efectos de los fármacos , Insuficiencia Cardíaca/fisiopatología , Vasodilatadores/farmacología , Anciano , Arginina/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vasodilatadores/uso terapéuticoRESUMEN
BACKGROUND: Vascular wall remodeling is a major factor contributing to restenosis after angioplasty that involves migration and proliferation of vascular smooth muscle cells. The release of matrix-degrading metalloproteinases, including metalloproteinase-2 and metalloproteinase-9, facilitates remodeling. Experimental data suggest that nitric oxide (NO) decreases the activity of metalloproteinases and this may attenuate arterial remodeling after balloon injury. We investigated whether metalloproteinase-2, metalloproteinase-9 and NO are released into the coronary sinus blood during angioplasty in coronary patients. METHODS: In 10 patients with stable angina undergoing elective percutaneous transluminal coronary angioplasty of an isolated stenosis of the proximal left anterior descending coronary artery, blood was sampled from the coronary sinus at baseline, immediately and 1 min after each balloon deflation. Plasma release of metalloproteinase-2 and metalloproteinase-9 was assayed by their gelatinolytic activity using zymography, while the liberation of NO metabolites was measured by high-performance liquid chromatography. RESULTS: Two consecutive balloon inflations each of 60 s duration, resulted in an immediate increase (P<0.05) of metalloproteinase-9, but not metalloproteinase-2 activity, followed by normalization of metalloproteinase-9 levels to the baseline within 1 min. Plasma levels of NO metabolites remained unchanged. CONCLUSIONS: Rapid release of metalloproteinase-9 after balloon inflation may both contribute to remodeling and protect the vascular wall from post-angioplasty thrombosis.