Asociación entre el volumen plaquetario medio y la resistencia a aspirina e inhibidores del receptor p2y12 en pacientes ancianos con síndrome coronario agudo / Association between Mean Platelet Volume and Resistance to Aspirin and P2Y12 Receptor Inhibitors in Elderly Patients with Acute Coronary Syndrome

RESUMEN Introducción: La resistencia a antiagregantes y el volumen plaquetario medio (VPM) son predictores de eventos en el síndrome coronario agudo (SCA). La asociación entre ambos ha sido poco estudiada. Objetivos: Evaluar si existe asociación entre la resistencia a la aspirina (AAS) e inhibidores del receptor P2Y12 (iP2Y12) y el VPM en pacientes mayores de 65 años con SCA. Material y métodos: Se incluyeron pacientes mayores de 65 años con diagnóstico de SCA. Se dividieron en: grupo 1 (resistencia a ambos antiagregantes), grupo 2 (a uno de los antiagregantes) y grupo 3 (a ningún antiagregante). Se midió la agregación plaquetaria entre las 12 y 24 horas poscarga (por light transmission aggregometry). Se consideró resistencia a iP2Y12 a un porcentaje máximo de agregación (PMA) con ADP > 60% y a la AAS a un PMA con ARA > 20%. En el seguimiento se consi-deró el punto final combinado de muerte global y reinternación cardiovascular. Resultados: Se incluyeron 195 pacientes que recibieron AAS e iP2y12 (120 recibieron clopidogrel y 75 ticagrelor); grupo 1 (19%), grupo 2 (34,4%) y grupo 3 (46,6%). El VPM se asoció a la resistencia a ambos antiagregantes (OR 1,02 (IC 95% 1,01-1,05), p = 0,03. A su vez, el VPM y el GRACE fueron predictores independientes del punto combinado (HR 1,03 (IC 95% 1,01-1,07), p = 0,04 y HR 1,02 (IC 95% 1,01-1,04), p = 0,02), respectivamente. Conclusiones: El VPM se asoció a la presencia de resistencia a ambos antiagregantes. En el seguimiento el VPM y el score GRACE fueron predictores del punto combinado.

ABSTRACT Background: Antiplatelet resistance and mean platelet volume (MPV) are event predictors in acute coronary syndrome (ACS). However, the association between both has been poorly studied. Objective: The aim of this study was to evaluate the association between MPV and resistance to aspirin (ASA) and P2Y12 receptor inhibitors (P2Y12i) in elderly patients with ACS. Methods: Patients over 65 years old with diagnosis of ACS were included in the study. They were divided into group 1 (re-sistance to both antiplatelet agents), group 2 (resistance to one antiplatelet agent) and group 3 (no resistance to antiplatelet agents). Platelet aggregation was measured between 12 and 24 hours postload (by light transmission aggregometry). Resis-tance to P2Y12i was considered as maximum percentage of aggregation (MPA) with adenosine diphosphate (ADP) >60% and resistance to ASA as MPA with arachidonic acid (ARA) >20%. The composite endpoint of global death and cardiovascular re-hospitalization was considered during follow-up. Results: One hundred and ninety five patients included in the study received ASA and P2Y12i (120 received clopidogrel and 75 ticagrelor). Nineteen percent of patients belonged to group 1, 34.4% to group 2 and 46.6% to group 3. Mean platelet volume was associated with resistance to both antiplatelet agents [OR 1.02 (95% CI 1.01-1.05), p=0.03], while MPV and the GRACE score were independent predictors of the composite endpoint [HR 1.03 (95% CI 1.01-1.07), p=0.04] and [HR 1.02 (95% CI 1.01-1.04), p=0.02], respectively. Conclusions: Mean platelet volume was associated with the presence of resistance to both antiplatelet agents. During follow-up, MPV and the GRACE score were predictors of the composite endpoint.

Renal damage induced by the pesticide methyl parathion in male Wistar rats.

Little information is apparently available regarding the nephrotoxic effects induced by pesticides. The aim of this study was to examine the influence of low doses of methyl parathion (MP) on the structure and function of the kidney of male Wistar rats. A corn oil (vehicle) was administered to control rats, whereas treated rats received MP at 0.56 mg/kg orally (1/25 of LD50), every third day, for 8 weeks. At the end of each week following MP exposure, creatinine and glucose levels were measured in plasma, while glucose, inorganic phosphate, total proteins, albumin, and activity of γ-glutamyltranspeptidase (GGT) were determined in urine. Kidney histological study was also performed. Compared with control rats, MP significantly increased plasma glucose and creatinine levels accompanied by decreased urinary flow rate and elevated urinary excretion rates of glucose, phosphate, and albumin. Further, the activity of GGT in urine was increased significantly. The proximal cells exhibited cytoplasmic vacuolization, positive periodic acid Schiff inclusions, and brush border edge loss after 2 or 4 weeks following MP treatment. Finally, renal cortex samples were obtained at 2, 4, 6, and 8 weeks of MP treatment, and the concentrations of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity were measured. The mRNA expression levels of BAX and tumor necrosis factor-α (TNF-α) were also determined (RT-PCR). MP significantly decreased renal GSH levels, increased GPx activity, as well as downregulated the mRNA expression of TNF-α and BAX. Densitometry analysis showed a significant reduction in TNF-α and BAX mRNA expression levels at 2 and 4 weeks following MP treatment. Low doses of MP produced structural and functional damage to the proximal tubules of male rat kidney.

Embolia de líquido amniótico que debuta como asistolia durante el trabajo de parto / Amniotic fluid embolism manifesting as asystole during labor

La embolia de líquido amniótico (ELA) constituye una entidad infrecuente en el embarazo o posparto, pero sus consecuencias pueden ser devastadoras tanto para la madre como para el feto. Presentamos el caso de una paciente primípara de 35 años que súbitamente durante el trabajo de parto presenta una parada cardiaca, iniciándose maniobras de RCP avanzada y cesárea peri-mortem. La evolución es mala, con múltiples complicaciones cardiovasculares y coagulopatía importante que precisa de histerectomía. Desenlace fatal a los 8 días de la madre y a los 5 días del recién nacido. La incidencia de la ELA, según los más recientes estudios realizados sobre bases poblacionales extensas, se sitúa entre 1/15.000 y 1/50.000 partos, con una mortalidad que clásicamente se sitúa entorno al 60-80%. La terapéutica se basa en gran parte en medidas de sostén y tratamiento sintomático. Las principales complicaciones son hemorrágicas, cardiovasculares y respiratorias. Se instauran medidas de soporte vital avanzado tan pronto como sea posible, dirigidas al mantenimiento de la oxigenación, la circulación y la coagulopatía(AU)

Amniotic fluid embolism (AFE) is infrequent in pregnancy or the postpartum, but the consequences can be devastating for both the mother and the fetus. We report the case of a 35-year-old primipara with sudden cardiac arrest during labor. Advanced cardiopulmonary resuscitation and peri-mortem cesarean section were performed. The clinical course was poor with multiple cardiovascular complications and severe coagulopathy, requiring hysterectomy. The patient died at 8 days and the neonate at 5 days. According to the most recent broad population-based studies, the incidence of AFE is between 1/15000 and 1/50000 childbirths, with mortality that is classically around 60-80%. Treatment is largely based on support measures and symptomatic treatment. The principal complications are hemorrhagic, cardiovascular and respiratory. Advanced life support measures should be started as soon as possible, aiming to maintain oxygen supply and circulation and arrest coagulopathy(AU)

The flavonoid quercetin protects and prevents against potassium dichromate-induced systemic peroxidation of lipids and diminution in renal clearance of para-aminohippuric acid and inulin in the rat.

It is well known that exposure to chromium (Cr) can lead to nephrotoxicity. Quercetin is a flavonoid of interest because of its proposed health-promoting effects. The aim of this work was to elucidate the role of quercetin against the nephrotoxicity caused by Cr in rats. Quercetin may have positive effects in combating, or helping to prevent, nephrotoxicity. It was observed that a single dose of potassium dichromate resulted in both an increase of systemic peroxidation of lipids and a decrease of the renal clearance of para-aminohippuric acid and inulin. Our results show that treatment with quercetin protected and prevented against these damaging effects.

Potassium dichromate-induced changes on urinary-specific activities of gamma-glutamyl transpeptidase and alanine aminopeptidase enzymes.

It has been reported that potassium dichromate-induced nephrotoxicity is evidenced by diminution in creatinine clearance, increase in urinary protein, and structural damage to the proximal tubules. Damage to tissue often leads to the release of enzymes from the injured cells into the extracellular fluids. The aim of this study was to establish whether potassium dichromate induces changes in the urinary-specific activities of gamma-glutamyl transpeptidase and alanine aminopeptidase enzymes. Our results show that the administration of a single intraperitoneal dose of potassium dichromate decreased the activity of such enzymes in urine.

Acute renal failure induced by carbon tetrachloride in rats with hepatic cirrhosis.

Relationship between cirrhosis and renal dysfunction is not yet fully understood. A model of cirrhosis with acute hepatic and renal damage (RF), produced by CCl4 in rats, with hemodynamic and renal functional alterations, similar to those observed in decompensated cirrhosis (DC) in man, was used to study chemical nephrotoxicity in animals. We performed in male Wistar rats hepatic and renal functional and hemodynamic studies in control, cirrhotic and decompensated cirrhotic (DC) groups. Cirrhosis was induced with carbon tetrachloride by chronic administration. Association between liver and renal functional alterations was detected in rats with decompensated cirrhosis, showing fall in mean arterial pressure and reduction of glomerular filtration rate and filtration fraction. Renal hemodynamics did not change in cirrhotic rats, similarly to what occurs in compensated cirrhotic patients. However, DC rats exhibited increased sodium, glucose and phosphate urinary excretions and decreased ATP in renal cortex. DC animals had severe hypoglycemia. There was an extensive liver fibrosis. Glomeruli had hypercellularity and tubules showed extensive vacuolization in cirrhotic and DC rats. The present study suggests that in this model, damage typical of acute tubular necrosis ensues in cirrhotic rats. We describe functional and morphological damage in liver and kidney in a model of cirrhosis that might predispose to the development of acute renal failure when an individual with hepatic damage is exposed in acute way to chemical toxicants.