title: Effect of intravenous administration of antioxidants alone and in combination on myocardial reperfusion injury in an experimental pig model.
abstract: BACKGROUND
  Several antioxidants have been found to have conflicting results in attenuating myocardial reperfusion injury. These studies were done primarily in experimental protocols that did not approximate clinical situations.
  
  
  OBJECTIVE
  The aim of this study was to test the efficacy of 3 different antioxidants (ascorbic acid [AA], desferrioxamine, and N-acetylcysteine [NAC]) administered IV alone and in combination in a closed-chest pig model.
  
  
  METHODS
  Farm-raised domestic male pigs (aged 3-5 months, weight of 30-35 kg) were assigned to 1 of 5 groups to receive treatment as follows: group A, AA 100 mg/kg; group B, desferrioxamine 60 mg/kg; group C, a loading dose of NAC 100 mg/kg for 20 minutes and a 20-mg/kg maintenance dose; group D, all 3 drugs in combination; and group E, normal saline (control group). The infusion of all drugs was started 15 minutes before and completed 5 minutes after reperfusion, except for the administration of NAC, which was terminated 60 minutes postreperfusion. Myocardial ischemia (45 minutes) and reperfusion (210 minutes) were achieved percutaneously by circumflex artery balloon occlusion. Ejection fraction, left ventricular end-diastolic pressure (LVEDP), flow in the infarcted artery, and all ventricular arrhythmias were recorded. Oxidative stress was estimated by serial measurements of thiobarbituric acid reactive substance (TBARS) concentration in coronary sinus blood. Infarct size was assessed as a percentage of the area at risk (I/R ratio) using the tetrazolium red staining method.
  
  
  RESULTS
  The 25 pigs were divided into 5 groups of 5 pigs each. No significant between-group differences were found in I/R ratio or in oxidative stress (as measured by TBARS concentration). Group C developed significantly more ventricular atrhythmias than the control group (80% vs 0%, P = 0.02). No other differences among groups were found. LVEDP was significantly elevated in all treatment groups (mean LVEDP difference [SD] for group A, 6.0 [1.6] mm Hg; group B, 17.6 [1.9] mm Hg; group C, 3.6 [1.7] mm Hg; group D, 6.8 [3.2] and group E, 5.4 [3.4] mm Hg). LVEDP elevation was found to be significantly higher in group B compared with all the other groups (all, P < 0.001). No significant between-group differences were found in the other parameters measured.
  
  
  CONCLUSIONS
  In this experimental pig model, the antioxidants AA, desferrioxamine, and NAC administered alone or in combination did not reduce the deleterious effects of reperfusion injury and specifically the extent of myocardial necrosis.
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece.
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Nikas
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Chatziathanasiou
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Kotsia
authors.affiliation: Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Papamichael
authors.affiliation: Department of Physiology, Ioannina Medical School, Ioannina, Greece.
authors.forename: Christoforos
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece.
authors.forename: Michail
authors.initials: M
authors.lastname: Papafaklis
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece ; Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Katerina K
authors.initials: KK
authors.lastname: Naka
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Kazakos
authors.affiliation: Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Haralampos J
authors.initials: HJ
authors.lastname: Milionis
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Vakalis
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece ; Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Katsouras
authors.affiliation: Department of Forensic Medicine, Ioannina Medical School, Ioannina, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Mpoumpa
authors.affiliation: Department of Forensic Medicine, Ioannina Medical School, Ioannina, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vougiouklakis
authors.affiliation: Michaelideion Cardiac Centre, Ioannina Medical School, Ioannina, Greece ; Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Lampros
authors.initials: L
authors.lastname: Michalis
keywords: antioxidants; combination; myocardial infarction; reperfusion injury