title: Amelioration of persistent left ventricular function impairment through increased plasma ascorbate levels following myocardial infarction.
abstract: OBJECTIVE
  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.
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Valls
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Gormaz
authors.affiliation: b Cardiovascular Department , San Juan de Dios Hospital , Santiago , Chile.
authors.forename: Rubén
authors.initials: R
authors.lastname: Aguayo
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: González
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Brito
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hasson
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Matías
authors.initials: M
authors.lastname: Libuy
authors.affiliation: c Department of Radiology , University of Chile Clinical Hospital , Santiago , Chile.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Ramos
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carrasco
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.|d Cardiovascular Department , University of Chile Clinical Hospital , Santiago , Chile.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Prieto
authors.affiliation: d Cardiovascular Department , University of Chile Clinical Hospital , Santiago , Chile.
authors.forename: Gastón
authors.initials: G
authors.lastname: Dussaillant
authors.affiliation: b Cardiovascular Department , San Juan de Dios Hospital , Santiago , Chile.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Puentes
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Viviana
authors.initials: V
authors.lastname: Noriega
authors.affiliation: a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile , Santiago , Chile.
authors.forename: Ramón
authors.initials: R
authors.lastname: Rodrigo
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001205:Ascorbic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D018384:Oxidative Stress / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D001205:Ascorbic Acid
keywords: Myocardial infarction; Oxidative stress; Ventricular ejection fraction; Vitamin C