title: Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response.
abstract: Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 °C, followed by re-warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-α). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation.
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Steinbrenner
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Esra
authors.initials: E
authors.lastname: Bilgic
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University, Düsseldorf, Germany.|Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Engels
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University, Düsseldorf, Germany.|Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Wollschläger
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Döhrn
authors.affiliation: Clinic for Anaesthesiology, Klinikum rechts der Isar, Technische Universität, Munich, Germany.
authors.forename: Kristine
authors.initials: K
authors.lastname: Kellermann
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany. udo.boeken@med.uni-duesseldorf.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Boeken
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
mesh_terms: D000818:Animals; D001393:Azoles / Q000008:administration & dosage* / Q000494:pharmacology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D019587:Dietary Supplements; D007036:Hypothermia, Induced / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy; D054833:Isoindoles; D007964:Leukocytosis / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D058958:Organs at Risk / Q000293:injuries; D010766:Phosphorylation / Q000187:drug effects; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000178:diet therapy / Q000188:drug therapy / Q000517:prevention & control*; D012643:Selenium / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D012643:Selenium
keywords: cardioprotection; cardiopulmonary bypass; deep hypothermic circulatory arrest; ischemia/reperfusion injury; selenium