title: Hemoglobin-associated oxidative stress in the pericardial compartment of postoperative cardiac surgery patients.
abstract: Atherosclerosis and valvular heart disease often require treatment with corrective surgery to prevent future myocardial infarction, ischemic heart disease, and heart failure. Mechanisms underlying the development of the associated complications of surgery are multifactorial and have been linked to inflammation and oxidative stress, classically as measured in the blood or plasma of patients. Postoperative pericardial fluid (PO-PCF) has not been investigated in depth with respect to the potential to induce oxidative stress. This is important because cardiac surgery disrupts the integrity of the pericardial membrane surrounding the heart and causes significant alterations in the composition of the pericardial fluid (PCF). This includes contamination with hemolyzed blood and high concentrations of oxidized hemoglobin, which suggests that cardiac surgery results in oxidative stress within the pericardial space. Accordingly, we tested the hypothesis that PO-PCF is highly pro-oxidant and that the potential interaction between inflammatory cell-derived hydrogen peroxide with hemoglobin is associated with oxidative stress. Blood and PCF were collected from 31 patients at the time of surgery and postoperatively from 4 to 48 h after coronary artery bypass grafting, valve replacement, or valve repair (mitral or aortic). PO-PCF contained high concentrations of neutrophils and monocytes, which are capable of generating elevated amounts of superoxide and hydrogen peroxide through the oxidative burst. In addition, PO-PCF primed naive neutrophils resulting in an enhanced oxidative burst upon stimulation. The PO-PCF also contained increased concentrations of cell-free oxidized hemoglobin that was associated with elevated levels of F2α isoprostanes and prostaglandins, consistent with both oxidative stress and activation of cyclooxygenase. Lastly, protein analysis of the PO-PCF revealed evidence of protein thiol oxidation and protein carbonylation. We conclude that PO-PCF is highly pro-oxidant and speculate that it may contribute to the risk of postoperative complications.
authors.affiliation: 1] Department of Pathology, Mitochondrial Medicine Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA [2] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kramer
authors.affiliation: 1] Department of Pathology, Mitochondrial Medicine Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA [2] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Balu K
authors.initials: BK
authors.lastname: Chacko
authors.affiliation: 1] Department of Pathology, Mitochondrial Medicine Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA [2] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Saranya
authors.initials: S
authors.lastname: Ravi
authors.affiliation: 1] Department of Pathology, Mitochondrial Medicine Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA [2] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Johnson
authors.affiliation: 1] Department of Pathology, Mitochondrial Medicine Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA [2] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Tanecia
authors.initials: T
authors.lastname: Mitchell
authors.affiliation: 1] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA [2] Targeted Metabolomics and Proteomics Laboratory, Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Targeted Metabolomics and Proteomics Laboratory, Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Arabshahi
authors.affiliation: 1] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA [2] Division of Cardiovascular Sciences, Department of Medicine, Center for Heart Failure Research, University of Alabama at Birmingham, Birmingham, AL, USA [3] Department of Veterans Affairs Medical Center, Birmingham, AL, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: George
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.affiliation: 1] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA [2] Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: George
authors.affiliation: 1] Department of Pathology, Mitochondrial Medicine Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA [2] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Darley-Usmar
authors.affiliation: 1] Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA [2] Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Melby
mesh_terms: D000704:Analysis of Variance; D001772:Blood Cell Count; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004591:Electrophoresis, Polyacrylamide Gel; D045604:Extracellular Fluid / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000378:metabolism; D005434:Flow Cytometry; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D013058:Mass Spectrometry; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010496:Pericardium / Q000378:metabolism / Q000503:physiopathology*; D011183:Postoperative Complications / Q000503:physiopathology*; D050050:Protein Carbonylation; D012394:Rosaniline Dyes; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D028441:F2-Isoprostanes; D006454:Hemoglobins; D012394:Rosaniline Dyes; D013438:Sulfhydryl Compounds; C048139:Coomassie blue; D006861:Hydrogen Peroxide