Hernán Prat

Relationship between Oxidative Stress and Essential Hypertension

This study investigated the association of blood pressure with blood oxidative stress–related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=−0.46, p<0.009 and r=−0.48, p<0.007), plasma vitamin C levels (r=−0.53, p<0.003 and r=−0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress–related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.

Decrease in oxidative stress through supplementation of vitamins C and E is associated with a reduction in blood pressure in patients with essential hypertension

Oxidative stress has been associated with mechanisms of EH (essential hypertension). The aim of the present study was to test the hypothesis that the antioxidant properties of vitamins C and E are associated with a decrease in BP (blood pressure) in patients with EH. A randomized double-blind placebo-controlled clinical trial was conducted in 110 men with grade 1 EH (35-60 years of age without obesity, dyslipidaemia and diabetes mellitus, non-smokers, not undergoing vigorous physical exercise, without the use of any medication and/or high consumption of fruit and vegetables). Participants were randomly assigned to receive either vitamins C+E [vitamin C (1 g/day) plus vitamin E (400 international units/day)] or placebo for 8 weeks. Measurements included 24 h ambulatory BP and blood analysis of oxidative-stress-related parameters in erythrocytes (GSH/GSSH ratio, antioxidant enzymes and malondialdehyde) and plasma [FRAP (ferric reducing ability of plasma)], and levels of 8-isoprostane, vitamins C and E were measured at baseline and after treatment. Following administration of vitamins C+E, patients with EH had significantly lower systolic BP, diastolic BP and mean arterial BP and higher erythrocyte and serum antioxidant capacity compared with either placebo-treated patients with EH or the patients with EH at baseline prior to treatment. BP correlated positively with plasma 8-isoprostane levels and negatively with plasma FRAP levels in the vitamins C+E- and placebo-treated groups. In conclusion, the present study supports the view that oxidative stress is involved in the pathogenesis of EH, and that enhancement of antioxidant status by supplementation with vitamins C and E in patients with EH is associated with lower BP. This suggests intervention with antioxidants as an adjunct therapy for hypertension.

Is Ouabain Produced by the Adrenal Gland

1. Ouabain or a related stereoisomer, termed endogenous ouabain, has been identified in adrenal cortex tissue and culture medium from adrenocortical cells. 2. Angiotensin II and adrenocorticotropin, the main activators of aldosterone secretion from adrenal glomerulosa cells appear to increase the production of this compound. 3. The purpose of this review is to briefly discuss recent available experimental evidence suggesting that endogenous ouabain is secreted by the zona glomerulosa of the adrenal gland.

Seguimiento clínico en pacientes con buena capacidad metabólica en la prueba de esfuerzo con SPECT miocárdico

BACKGROUND The evaluation of coronary artery disease (CAD) can be performed with stress test and myocardial SPECT tomography. AIM To assess the predictive value of myocardial SPECT using stress test for cardiovascular events in patients with good exercise capacity. MATERIAL AND METHODS We included 102 males aged 56 ± 10 years and 19 females aged 52 ± 10 years, all able to achieve 10 METs and ≥ 85% of the theoretical maximum heart rate and at least 8 min in their stress test with gated 99mTc-sestamibi SPECT. Eighty two percent of patients were followed clinically for 33 ± 17 months. RESULTS Sixty seven percent of patients were studied for CAD screening and the rest for known disease assessment. Treadmill stress test was negative in 75.4%; 37% of patients with moderate to severe Duke Score presented ischemia. Normal myocardial perfusion SPECT was observed in 70.2%. Reversible defects appeared in 24.8% of cases, which were of moderate or severe degree (> 10% left ventricular extension) in 56.6%. Only seven cases had coronary events after the SPECT. Two major (myocardial infarction and emergency coronary revascularization) and 5 minor events (elective revascularization) ere observed in the follow-up. In a multivariate analysis, SPECT ischemia was the only statistically significant parameter that increased the probability of having a major or minor event. CONCLUSIONS Nearly a quarter of our patients with good exercise capacity demonstrated reversible defects in their myocardial perfusion SPECT. In the intermediate-term follow-up, a low rate of cardiac events was observed, being the isotopic ischemia the only significant predictive parameter.

Daño vascular asociado a uso de cocaína: Caso clínico

BACKGROUND Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. We report a 39-year-old male addicted to cocaine, who presented with three consecutive ischemic events characterized by an acute myocardial infarction and two ischemic strokes complicated by cardiac failure and severe neurological sequelae. The pathophysiology of cocaine-induce vascular damage and the management of the ischemic complications are discussed.

Valor del índice de excentricidad del ventrículo izquierdo con tomografía spect de perfusión miocárdica en diversas condiciones

Resumen:Introduccion: El indice de excentricidad (IE) obtenido con SPECT miocardico permite evaluacion de esfericidad ventricular izquierda en remodelacion patologica. Objetivo: conocer IE en adultos con diversas con-diciones cardiacas. Metodo: Grupo I: Controles (n=44) con >2 fac-tores de riesgo cardiovascular exceptuando Diabe-tes Mellitus (DM); Grupo II: DM 2 (n=41). Ambos grupos asintomaticos sin enfermedad coronaria co-nocida. Grupo III: Con alteracion de motilidad seg-mentaria y/o infarto de miocardio (n=64). Grupo IV: Dilatados (n=21) con alteraciones de motilidad difu-sa o miocardiopatias. Se utilizo Sestamibi-Tc99m y procesamiento QGS. (IE esfera valor ≈0). Resultados: Las fracciones de eyeccion del ven-triculo izquierdo fueron significativamente mayores en grupos I y II que en grupos III y IV y los volu-menes de fin de diastole menores. Los IE en reposo fueron: Grupo I: 0.889±0.003; Grupo II: 0.873±0.03; Grupo III: 0.846±0.04 y Grupo IV: 0.820±0.06. Prueba t de student entre Grupos: I vs II (p=0.028); I vs III asi como I vs IV (p<0.0001). Sin embargo, el analisis multivariado ANOVA no mostro diferen-cia entre los grupos I vs II ni entre grupos III vs IV, aunque si entre I y II vs III y IV. El IE fue menor en grupos con alteraciones de motilidad que sin estas (p<0.001). No hubo Controles del Grupo I con fun-cion normal con IE <0.82. Los hallazgos de IE post estres fueron similares.

Estratificación de riesgo de muerte a mediano plazo de pacientes evaluados por enfermedad coronaria con SPECT de perfusión miocárdica bajo efecto de dipiridamol

BACKGROUND Dipyridamole (DIP) is the most commonly employed pharmacological stressor for myocardial perfusion tomography (SPECT) in patients unable to reach an adequate work load. AIM To assess the predictive capacity of DIP SPECT on survival. MATERIAL AND METHODS We included 985 adults aged 66 ±11 years (45% women) with rest and DIP-SPECT. The main indications for the procedure were coronary artery disease (CAD) screening in 66% and known CAD in 33%. Participants were followed up for a median of 65 months (interquartile range 54 to 86 months). During the follow up, 261 deaths were recorded and 98% had a specified cause in their death certificate. RESULTS Myocardial SPECT was abnormal in 44% of participants. Transient ischemic defects were observed in 34%, fixed defects concordant with infarction in 27% and post-stress systolic dysfunction in 23%. Twenty five percent of deaths were attributable to cardiac or ischemic cause and 22% to cancer. In a bivariate analysis, the hazard ratio (HR) of death of any cause was lower in females and higher in the presence of CAD. The multivariate analysis showed that being older than 46 years increased the HR of death of any cause. In a bivariate analysis, the HR for cardiac death was higher when the myocardial SPECT showed ischemia, necrosis or left ventricular dilation. In the multivariate analysis, post-stress left ventricular systolic function was associated with a lower risk of cardiac death. CONCLUSIONS An abnormal myocardial SPECT, perfusion abnormalities, left ventricular systolic function or dilation are independent predictors of cardiac death in these participants.

SEGUIMIENTO A CINCO AÑOS EN PACIENTES DIABÉTICOS SIN SÍNTOMAS CARDÍACOS ESTUDIADOS CON PERFUSIÓN MIOCÁRDICA

Se estudiaron 40 pacientes asintomati-cos coronarios, con DM conocida por ≥5 anos, >45 anos de edad, con ≥2 factores de riesgo cardiovascular (FRCV) y electrocardiograma basal normal o con al-teraciones inespecificas. Todos efectuaron una prueba de esfuerzo (PE) adecuada y se estudiaron con Sesta-mibi-Tc99m repetido en 32 casos al 3o ano. Ademas, se evaluo a 36 controles no diabeticos con >2 FRCV. El seguimiento fue de 64±11 meses.

VALIDACIÓN DEL TEST DE TROPONINAS EN PLASMA A PARTIR DE UNA POBLACIÓN SANA. UNA EXPERIENCIA LOCAL

Las troponinas corresponden a pro-teinas estructurales del miocardiocito, su presencia en plasma se utiliza como marcador de injuria miocardica. El test troponinas en plasma se utiliza actualmente para detectar dano miocardico en pacientes en quienes se sos -pecha un infarto agudo al miocardio; para este proposito se toma como referencia valores de referencia validados en poblaciones de Inglaterra o Estados Unidos.

Enfermedad cerebrovascular y estatinas

Summary: Cerebrovascular disease is one of the leading causes of death in Chile. Its main manifestation, CVA, is most frequent in elderly subjects. Approximately 70% of CVA recognize an ischemic origin, the rest corresponds to intracerebral bleeding episodes. In several studies the prior use of statins has been proven to reduce the incidence of CVA as well as improving their prognosis, in spite of a lack of significant correlation with statins effects on serum cholesterol. Statin effects have been related to their pleiotropic properties, to reductions in Protein C levels and to activation of endothelial stem cells. American Stroke Association Guidelines (2011) recommend statins for CVA in subjects with high cardiovascular risk. Triglycerides have not been clearly shown to be a risk factor for CVA and no other lipid lowering agents are recommended in this setting