Effect of Repeated Exposure to Sevoflurane on Electroencephalographic Alpha Oscillation in Pediatric Patients Undergoing Radiation Therapy: A Prospective Observational Study.

BACKGROUND: Pharmacological tolerance is defined as a decrease in the effect of a drug over time, or the need to increase the dose to achieve the same effect. It has not been established whether repeated exposure to sevoflurane induces tolerance in children. METHODS: We conducted an observational study in children younger than 6 years of age scheduled for multiple radiotherapy sessions with sevoflurane anesthesia. To evaluate the development of sevoflurane tolerance, we analyzed changes in electroencephalographic spectral power at induction, across sessions. We fitted individual and group-level linear regression models to evaluate the correlation between the outcomes and sessions. In addition, a linear mixed-effect model was used to evaluate the association between radiotherapy sessions and outcomes. RESULTS: Eighteen children were included and the median number of radiotherapy sessions per child was 28 (interquartile range: 10 to 33). There was no correlation between induction time and radiotherapy sessions. At the group level, the linear mixed-effect model showed, in a subgroup of patients, that alpha relative power and spectral edge frequency 95 were inversely correlated with the number of anesthesia sessions. Nonetheless, this subgroup did not differ from the other subjects in terms of age, sex, or the total number of radiotherapy sessions. CONCLUSIONS: Our results suggest that children undergoing repeated anesthesia exposure for radiotherapy do not develop tolerance to sevoflurane. However, we found that a group of patients exhibited a reduction in the alpha relative power as a function of anesthetic exposure. These results may have implications that justify further studies.

Techniques and Complications of Anesthesia in Pediatric Radiotherapy: A Retrospective Cohort Study.

BACKGROUND: Anesthesia during pediatric external beam radiation therapy poses a challenge, as radiotherapy rooms are not designed for the administration of anesthesia. AIMS: We conducted a retrospective cohort study of children who underwent radiation therapy to describe the anesthetic approach and assess anesthetic-related complications. MATERIALS AND METHODS: Data of all, who underwent radiation therapy under general anesthesia between November 2019 and January 2021, were recorded. Data were obtained from medical records, including demographic characteristics and information, regarding the anesthetic procedure and its associated complications. We describe our protocols for preoperative assessment, anesthetic procedures, and postanesthetic discharge evaluation. RESULTS: Over the reporting period, 739 sessions of general anesthesia were performed. The mean number of radiation therapy rounds per patient was 23.5 sessions. Anesthetic induction was accomplished by sevoflurane inhalation in 639 sessions (86.4%) and intravenous propofol in the remaining 13.6%. General anesthesia was maintained with sevoflurane in all cases. Anesthesia-related complications occurred in 118 sessions (15.7%). The most frequent was nausea in 48 (6.4%) cases, followed by hypotension in 38 (5.1%). Airway-related complications occurred at a low frequency (2.3%), and all were resolved successfully with positive pressure ventilation. No patient hospitalizations were required because of any anesthetic complications. CONCLUSIONS: Inhalation anesthesia is reliable and safe for pediatric patients undergoing radiation therapy.

Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support.

Purpose: Endothelial damage and angiogenesis are fundamental elements of neovascularisation and fibrosis observed in patients with coronavirus disease 2019 (COVID-19). Here, we aimed to evaluate whether early endothelial and angiogenic biomarkers detection predicts mortality and major cardiovascular events in patients with COVID-19 requiring respiratory support. Methods: Changes in serum syndecan-1, thrombomodulin, and angiogenic factor concentrations were analysed during the first 24 h and 10 days after COVID-19 hospitalisation in patients with high-flow nasal oxygen or mechanical ventilation. Also, we performed an exploratory evaluation of the endothelial migration process induced by COVID-19 in the patients' serum using an endothelial cell culture model. Results: In 43 patients, mean syndecan-1 concentration was 40.96 ± 106.9 ng/mL with a 33.9% increase (49.96 ± 58.1 ng/mL) at day 10. Both increases were significant compared to healthy controls (Kruskal-Wallis p < 0.0001). We observed an increase in thrombomodulin, Angiopoietin-2, human vascular endothelial growth factor (VEGF), and human hepatocyte growth factor (HGF) concentrations during the first 24 h, with a decrease in human tissue inhibitor of metalloproteinases-2 (TIMP-2) that remained after 10 days. An increase in human Interleukin-8 (IL-8) on the 10th day accompanied by high HGF was also noted. The incidence of myocardial injury and pulmonary thromboembolism was 55.8 and 20%, respectively. The incidence of in-hospital deaths was 16.3%. Biomarkers showed differences in severity of COVID-19. Syndecan-1, human platelet-derived growth factor (PDGF), VEGF, and Ang-2 predicted mortality. A multiple logistic regression model with TIMP-2 and PDGF had positive and negative predictive powers of 80.9 and 70%, respectively, for mortality. None of the biomarkers predicted myocardial injury or pulmonary thromboembolism. A proteome profiler array found changes in concentration in a large number of biomarkers of angiogenesis and chemoattractants. Finally, the serum samples from COVID-19 patients increased cell migration compared to that from healthy individuals. Conclusion: We observed that early endothelial and angiogenic biomarkers predicted mortality in patients with COVID-19. Chemoattractants from patients with COVID-19 increase the migration of endothelial cells. Trials are needed for confirmation, as this poses a therapeutic target for SARS-CoV-2.

Early Oxidative Stress Response in Patients with Severe Aortic Stenosis Undergoing Transcatheter and Surgical Aortic Valve Replacement: A Transatlantic Study.

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR. A total of 60 patients were prospectively enrolled in this exploratory study, 38 patients undergoing TAVR and 22 patients SAVR. Reduced and oxidized glutathione (GSH, GSSG) in red blood cells as well as the ferric-reducing ability of plasma (FRAP) and plasma concentrations of 8-isoprostanes were measured at baseline (S1), during early reperfusion (S2), and 6-8 hours (S3) following aortic valve replacement (AVR). TAVR and SAVR were successful in all patients. Patients undergoing TAVR were older (79.3 ± 9.5 vs. 74.2 ± 4.1 years; P < 0.01) and had a higher mean STS risk score (6.6 ± 4.8 vs. 3.2 ± 3.0; P < 0.001) than patients undergoing SAVR. At baseline, FRAP and 8-isoprostane plasma concentrations were similar between the two groups, but erythrocytic GSH concentrations were significantly lower in the TAVR group. After AVR, FRAP was markedly higher in the TAVR group, whereas 8-isoprostane concentrations were significantly elevated in the SAVR group. In conclusion, TAVR appears not to cause acute oxidative stress and may even improve the antioxidant capacity in the extracellular compartment.

Viable Pregnancy in a patient with metastatic melanoma treated with double checkpoint immunotherapy.

Metastatic cancers during pregnancy have historically been associated with dismal outcomes, with greater rates of tumor progression in part because of diminished treatment alternatives. Immunotherapy with T-cell checkpoint inhibitors has significantly impacted the survival of several metastatic tumors. However, given their mechanism of action, immune-related adverse events can occur, especially with combined immunotherapy treatments. During pregnancy, checkpoint pathways have a major role, providing immune tolerance to the fetal allograft. Furthermore, evidence suggests that inhibition of this pathway may be associated with an increased risk of miscarriage. We describe, to our knowledge, the first case reported in the literature of a patient 7 weeks pregnant, diagnosed with metastatic melanoma and treated with nivolumab plus ipilimumab. We also present the associated immune-related side effects and their treatment, as well as the oncologic results that lead to favorable pregnancy outcome.

Evaluación del consumo de antimicrobianos en una Unidad de Neonatologia: un trabajo en equipo para promover el uso racional de antimicrobianos / Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics

Resumen Antecedentes: Los antimicrobianos (ATM) son uno de los medicamentos más utilizados en recién nacidos (RN) hospitalizados. El uso indiscriminado de ATM trae consecuencias negativas como son el predominio de bacterias resistentes a los ATM usualmente utilizados y asociaciones individuales a morbilidad relevante como son la displasia broncopulmonar, enterocolitis necrosante, sepsis tardía y/o muerte. Objetivo: Registrar y evaluar las tendencias del uso de ATM a lo largo del tiempo en RN hospitalizados en el Servicio de Neonatología (SRN) del Complejo Asistencial Dr. Sótero del Río, con el fin de objetivar los cambios en la práctica habitual de la indicación de ATM. Un objetivo secundario fue evaluar el impacto de estas conductas sobre la resistencia antimicrobiana. Métodos: Estudio de cohorte, prospectivo, observacional, unicéntrico, en todos los pacientes hospitalizados entre enero de 2011 y diciembre de 2014. Se registró el peso al nacer, días de hospitalización, indicación y días de uso de ATM para cada paciente. El uso de ATM fue cuantificado por medio de distintas tasas: días de indicación de un o más ATM para el consumo global (TUA), sumatoria total de días de uso (STUA) como para los ATM más frecuentemente utilizados. Cada tasa calculada por 100 días hospitalizados. Además, se registró la susceptibilidad antimicrobiana de las bacterias más frecuentemente aisladas en nuestro servicio: Staphylococcus coagulasa negativa (SCN) y bacilos gramnegativos (BGNs). Resultados: El 34,7% de los pacientes hospitalizados recibió algún tipo de antimicrobiano, correspondiendo 32,3% a antibacterianos. El ATM más utilizado fue ampicilina (20,2% del total) y luego cefadroxilo (11,6%). El TUA no cambió entre 2011 y 2014. La STUA disminuyó en 10,7% entre 2011 y 2014 (p < 0,05). En el análisis por rangos de peso, en el grupo < 750 g disminuyó la tendencia de uso de vancomicina (descenso de uso en 9,9%) y un aumento de 18,8% para metronidazol. Por otra parte, hubo un aumento en el uso del régimen de piperacilina/tazobactam en el grupo > 1.500 g. Al evaluar la susceptibilidad antimicrobiana, hubo una disminución de la susceptibilidad a cloxacilina en SCN entre 2011 y 2014 desde 27 a 10,3%, respectivamente. Para BGN hubo una disminución desde 76,9 a 40,5% en la susceptibilidad a cefalosporinas de tercera generación, principalmente debido a Klebsiella pneumoniae que pasó a ser el BGN predominante, con un aumento de 6,7 a 50% en los años 2011 y 2014, respectivamente. Para Klebsiella pneumoniae la susceptibilidad a cefalosporinas de tercera generación descendió desde 77 a 22%. Por último, amikacina mostró una actividad sobre 85% en todos los BGNs entre 2011 y 2014. Conclusiones: Es recomendable planificar y mantener un registro continuo del consumo de ATM tanto como terapia y profilaxis, idealmente llevar el TUA, el STUA y siendo categorizado por tipo de ATM y rango de peso de los RN. En forma concomitante, es de considerable importancia analizar y evaluar la susceptibilidad de microorganismos. Es esencial que un equipo interdisciplinario prepare este registro, y que continuamente proporcione retroalimentación a los profesionales que mantienen el funcionamiento de las unidades de cuidados neonatales.

Background: Antibiotics (ATB) are drugs widely used in hospitalized newborns. The indiscriminate use of ATBs promote the rise of resistant bacteria to the most commonly indicated antimicrobials. In addition, ATB prescription presents associations to morbidity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, late sepsis and even death. All of the above leads to an increase in health care costs. Aim: To record and to evaluate trends of antibiotic use over time in hospitalized NB in the Neonatology Unit at Dr. Sótero del Río Hospital, in order to objectify the changes in the usual practice of the ATM indication. A secondary objective was to assess its impact on antimicrobial resistance. Methods: Cohort, observational, prospective unicenter study which included all hospitalized patients between January 2011 and December 2014. Birth weight, hospitalization days, ATB indication and days of ATB use were recorded for each patient. The use of ATB was quantified by means of different rates; days of indication of one or more ATBs for global consumption (RUA), total sum of days of use (TSUA) and for the most frequently used ATBs. Each calculated rate for 100 days hospitalized. In addition, the antimicrobial susceptibility of the most frequently isolated bacteria in our service: coagulase-negative Staphylococcus (SCN) and Gram-negative bacilli (BGN) were recorded continuously. Results: The 34.7% of the hospitalized patients received some type of antimicrobial agent. ATBs were 32.3% of medicines used. The most widely used was ampicillin (with 20.2% of the total) and cefadroxyl (with 11.6%). The RUA did not change during the study time, but STUA decreased by 10.7% between 2011 and 2014 with p < 0.05. When subgroup analyzes were divided by weight ranges, in the < 750 g group, the use of vancomycin decreased in use by 9.9% and an increase of 18.8% for metronidazole was observed. On the other hand, there was an increase in the use of the piperacillin-tazobactam regimen in the range > 1,500 g. When evaluating antimicrobial susceptibility, there was a decrease in susceptibility for oxacillin in SCN between 2011 and 2014 from 27% to 10.3% respectively. In addition, for Gram negative there was a decrease from 76.9% to 40.5% in susceptibility to third generation cephalosporins, mainly due to Klebsiella pneumoniae, which became the predominantly isolated BGN with an increase of 6.7% to 50% between 2011 and 2014, respectively. For K. pneumoniae the loss of susceptibility to third generation cephalosporins decreased from 77% to 22%. Finally, amikacin showed an activity over 85% in all BGNs between 2011 and 2014. Conclusions: It is advisable to plan and to maintain a continuous record of ATB consumption, as well as therapy and prophylaxis, being categorized by ATB type and range of newborn weight. It is of considerable importance to analyze and to evaluate the susceptibility of microorganisms. It is essential that an interdisciplinary team prepare this recording, and to continuously provide feedback to professionals who maintain the functioning of neonatal care units.

Effects of a novel ascorbate-based protocol on infarct size and ventricle function in acute myocardial infarction patients undergoing percutaneous coronary angioplasty.

INTRODUCTION: This study was designed to test the hypothesis that high-dose ascorbate prior to reperfusion followed by low chronic oral doses ameliorate myocardial reperfusion injury (MRI) in acute myocardial infarction patients subjected to primary percutaneous coronary angioplasty (PCA). MATERIAL AND METHODS: A randomized double-blind placebo-controlled and multicenter clinical trial was performed on acute myocardial infarction (AMI) patients who underwent PCA. Sodium ascorbate (320 mmol/l, n = 53) or placebo (n = 46) was infused 30 min prior to PCA. Blood samples were drawn at enrolment (M1), after balloon deflation (M2), 6-8 h after M2 (M3) and at discharge (M4). Total antioxidant capacity of plasma (ferric reducing ability of plasma - FRAP), erythrocyte reduced glutathione (GSH) and plasma ascorbate levels were determined in blood samples. Cardiac magnetic resonance (CMR) was performed at 7-15 days and 2-3 months following PCA. Ninety-nine patients were enrolled. In 67 patients, the first CMR was performed, and 40 patients completed follow-up. RESULTS: The ascorbate group showed significantly higher ascorbate and FRAP levels and a decrease in the GSH levels at M2 and M3 (p < 0.05). There were no significant differences in the infarct size, indexed end-systolic volume and ejection fraction at both CMRs. There was a significant amelioration in the decreased ejection fraction between the first and second CMR in the ascorbate group (p < 0.05). CONCLUSIONS: Ascorbate given prior to reperfusion did not show a significant difference in infarct size or ejection fraction. However, it improved the change in ejection fraction determined between 7-15 days and 2-3 months. This result hints at a possible functional effect of ascorbate to ameliorate MRI.

Role of Oxidative Stress in Renal Transplantation: Bases for an n-3 PUFA Strategy Against Delayed Graft Function.

Renal transplantation (RT) is considered the "gold standard" treatment for end-stage renal disease patients. Efforts should be made to reduce ischaemia-reperfusion (IR) injury, which unavoidably occurs in RT as long as several clinical settings, i.e. open-heart surgeries, prosthesis implantation, among others. It is well known that IR is primarily responsible for injury associated with RT. Consequently, tissue inflammation and organ dysfunction will ensue due to the occurrence of oxidative stress (OS) in the reperfused tissue, a condition generated when endogenous antioxidant defences become overwhelmed by a massive production of reactive oxygen species. Furthermore, OS is involved in the impairment of renal function, leading to deleterious conditions such as delayed graft function (DGF), which is a common clinical expression of IR injury in RT. Omega-3 polyunsaturated fatty acids (n -3 PUFA) have been widely used in different clinical settings to counteract the deleterious effects of OS. Thus, based on the currently available literature, the central aim of this review was to propose an n-3 PUFAbased strategy targeting the key role of OS in the pathophysiology of renal IR injury in order to encourage protection against the occurrence of DGF.

[Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics]. / Evaluación del consumo de antimicrobianos en una Unidad de Neonatologia: un trabajo en equipo para promover el uso racional de antimicrobianos.

BACKGROUND: Antibiotics (ATB) are drugs widely used in hospitalized newborns. The indiscriminate use of ATBs promote the rise of resistant bacteria to the most commonly indicated antimicrobials. In addition, ATB prescription presents associations to morbidity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, late sepsis and even death. All of the above leads to an increase in health care costs. AIM: To record and to evaluate trends of antibiotic use over time in hospitalized NB in the Neonatology Unit at Dr. Sótero del Río Hospital, in order to objectify the changes in the usual practice of the ATM indication. A secondary objective was to assess its impact on antimicrobial resistance. METHODS: Cohort, observational, prospective unicenter study which included all hospitalized patients between January 2011 and December 2014. Birth weight, hospitalization days, ATB indication and days of ATB use were recorded for each patient. The use of ATB was quantified by means of different rates; days of indication of one or more ATBs for global consumption (RUA), total sum of days of use (TSUA) and for the most frequently used ATBs. Each calculated rate for 100 days hospitalized. In addition, the antimicrobial susceptibility of the most frequently isolated bacteria in our service: coagulase-negative Staphylococcus (SCN) and Gram-negative bacilli (BGN) were recorded continuously. RESULTS: The 34.7% of the hospitalized patients received some type of antimicrobial agent. ATBs were 32.3% of medicines used. The most widely used was ampicillin (with 20.2% of the total) and cefadroxyl (with 11.6%). The RUA did not change during the study time, but STUA decreased by 10.7% between 2011 and 2014 with p < 0.05. When subgroup analyzes were divided by weight ranges, in the < 750 g group, the use of vancomycin decreased in use by 9.9% and an increase of 18.8% for metronidazole was observed. On the other hand, there was an increase in the use of the piperacillin-tazobactam regimen in the range > 1,500 g. When evaluating antimicrobial susceptibility, there was a decrease in susceptibility for oxacillin in SCN between 2011 and 2014 from 27% to 10.3% respectively. In addition, for Gram negative there was a decrease from 76.9% to 40.5% in susceptibility to third generation cephalosporins, mainly due to Klebsiella pneumoniae, which became the predominantly isolated BGN with an increase of 6.7% to 50% between 2011 and 2014, respectively. For K. pneumoniae the loss of susceptibility to third generation cephalosporins decreased from 77% to 22%. Finally, amikacin showed an activity over 85% in all BGNs between 2011 and 2014. CONCLUSIONS: It is advisable to plan and to maintain a continuous record of ATB consumption, as well as therapy and prophylaxis, being categorized by ATB type and range of newborn weight. It is of considerable importance to analyze and to evaluate the susceptibility of microorganisms. It is essential that an interdisciplinary team prepare this recording, and to continuously provide feedback to professionals who maintain the functioning of neonatal care units.

Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases.

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. It is widely accepted that oxidative stress plays a key role in their development and progression; hence oxidative damage might be abrogated by antioxidants. Polyphenols are phytochemicals showing extensively studied antioxidant properties in-vivo. Most representative sources of these compounds include fruits, greens, nuts, herbs, cocoa, tea and coffee. Epidemiological evidence suggests an association between the consumption of polyphenol-rich vegetables and the reduction of cardiovascular disease prevalence. This fact could be related to the anti-inflammatory, antithrombotic and vasodilatory effects of polyphenols. Even though these biological effects could be mainly attributed to the antioxidant activity of polyphenols, other pharmacological mechanisms should also be considered. The latter could comprise direct anti-inflammatory effects, modulation of intracellular signaling and gene expression, improvement of nitric oxide homeostasis, as well as platelet antiaggregation. However, it is noticeable that protocols of interventions to evaluate the properties of polyphenols have failed to show the same positive results reported from observational studies. At present, a controversy exists regarding the actual effectiveness of polyphenols in preventing cardiovascular diseases. Therefore, an improvement of the available knowledge about polyphenol pharmacokinetics, together with a better understanding of the mechanisms of action of these compounds, could be of great benefit. Thus, a rational support for the development of interventional designs could provide reliable evidence on the actual role of polyphenols in CVD prevention.

Amelioration of persistent left ventricular function impairment through increased plasma ascorbate levels following myocardial infarction.

PURPOSE: Percutaneous coronary angioplasty (PCA) has been demonstrated to reduce mortality and morbidity and thereby improve the prognosis of patients undergoing acute myocardial infarctions (AMIs). However, this procedure paradoxically increases the initial damage as the result of a condition known as 'myocardial reperfusion injury'. Oxidative stress may contribute to the mechanism of this injury. The goal of the present study was to ascertain whether high plasma ascorbate levels could ameliorate the reperfusion injuries that occur after the successful restoration of blood flow. METHODS: Patients from three clinical centers of the public health system were included in the study. The groups were formed by either-sex patients with a diagnosis of ST-segment elevation myocardial infarction with an indication for primary PCA. Only the patients who presented with their first myocardial infarction were enrolled. Ascorbate was administered through an infusion given prior to the restoration of the coronary flow, which was then followed by oral treatment with vitamin C (500 mg/12 hours) plus vitamin E (400 IU/day) for 84 days. The left ventricular ejection fraction (LVEF) was determined by using cardiac magnetic resonance on days 6 and 84 following the onset of the reperfusion. In addition, the microvascular function was assessed by an angiographic evaluation using the Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG). The results were grouped according to the plasma ascorbate concentration achieved immediately following the onset of reperfusion into either the HA group (high ascorbate, >1 mmol/l) or the LA group (low ascorbate, <1 mmol/l). The biochemical parameters were analyzed throughout the protocol. RESULTS: The LVEF of the HA group was significantly higher than that of the LA group, values on day 84 in the HA group were 33% higher than those of the LA group. The amelioration of the LVEF was accompanied by an improvement in the microvascular dysfunction, after PCA, 95% of the patients in the HA group achieved a TMPG of 2-3, in the LA group only 79% of patients showed a TMPG of 2-3. CONCLUSIONS: These data are consistent with the protective effect of high plasma levels of ascorbate against the oxidative challenge caused by reperfusion injury in patients subjected to PCA following an AMI. Further studies are needed to elucidate the mechanism accounting for this beneficial antioxidant effect.

Essential hypertension and oxidative stress: New insights.

Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.

The effectiveness of antioxidant vitamins C and E in reducing myocardial infarct size in patients subjected to percutaneous coronary angioplasty (PREVEC Trial): study protocol for a pilot randomized double-blind controlled trial.

BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Oxidative stress has been involved in the ischemia-reperfusion injury in AMI. It has been suggested that reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented.Therefore, we propose that antioxidant reinforcement through vitamins C and E supplementation should protect against the ischemia-reperfusion damage, thus decreasing infarct size.The PREVEC Trial (Prevention of reperfusion damage associated with percutaneous coronary angioplasty following acute myocardial infarction) seeks to evaluate whether antioxidant vitamins C and E reduce infarct size in patients subjected to percutaneous coronary angioplasty after AMI. METHODS/DESIGN: This is a randomized, 1:1, double-blind, placebo-controlled clinical trial.The study takes place at two centers in Chile: University of Chile Clinical Hospital and San Borja Arriarán Clinical Hospital.The subjects will be 134 adults with acute myocardial infarction with indication for percutaneous coronary angioplasty.This intervention is being performed as a pilot study, involving high-dose vitamin C infusion plus oral administration of vitamin E (Vitamin-treatment group) or placebo (Control group) during the angioplasty procedure. Afterward, the Vitamin-treatment group receives oral doses of vitamins C and E, and the Control group receives placebo for 84 days after coronary angioplasty.Primary outcome is infarct size, assessed by cardiac magnetic resonance (CMR), measured 6 and 84 days after coronary angioplasty.Secondary outcomes are ejection fraction, measured 6 and 84 days after coronary angioplasty with CMR, and biomarkers for oxidative stress, antioxidant status, heart damage, and inflammation, which will be measured at baseline, at the onset of reperfusion, 6 to 8 hours after revascularization, and at hospital discharge. DISCUSSION: The ischemia-reperfusion event occurring during angioplasty is known to increase myocardial infarct size. The cardioprotective benefits of high doses of vitamin C combined with vitamin E have not been fully explored. The PREVEC Trial seeks to determine the suitability of the therapeutic use of vitamins C and E against the reperfusion damage produced during angioplasty.Patient recruitment opened in February 2013. The trial is scheduled to end in March 2016. TRIAL REGISTRATION: ISRCTN56034553.