title: Plasma prohepcidin as a negative acute phase reactant after large cardiac surgery with a deep hypothermic circulatory arrest.
abstract: Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflammatory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9+/-10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48% fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance.
authors.affiliation: Institute of Pathological Physiology of the First Faculty of Medicine, Charles University, Prague, Czech Republic. maruna@LF1.cuni.cz
authors.forename: P
authors.initials: P
authors.lastname: Maruna
authors.forename: J
authors.initials: J
authors.lastname: Lindner
authors.forename: J
authors.initials: J
authors.lastname: Kunštýř
authors.forename: K
authors.initials: K
authors.lastname: Plocová
authors.forename: J
authors.initials: J
authors.lastname: Hubáček
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects; D015536:Down-Regulation; D004691:Endarterectomy / Q000009:adverse effects; D005260:Female; D064451:Hepcidins; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology / Q000601:surgery; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D011651:Pulmonary Artery / Q000601:surgery; D056346:Sternotomy / Q000009:adverse effects; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000209:etiology; D013923:Thromboembolism / Q000097:blood / Q000150:complications / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D064451:Hepcidins; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D011498:Protein Precursors