title: Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support.
abstract: In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidative stress in patients with decompensated CHF (congestive heart failure) and assessed whether clinical recompensation by short-term inotropic therapy influences these parameters. Patients with worsening CHF (n=29, aged 61.9+/-2.7 years), NYHA (New York Heart Association) class III-IV, and left ventricular ejection fraction of 23.7+/-1.8% were studied. Controls comprised age-matched healthy volunteers (n=15; 54.1+/-3.2 years). Plasma levels of cytokines [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein-1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE-selectin (soluble E-selectin)], systemic markers of oxidation [TBARS (thiobarbituric acid-reactive substances), 8-isoprostaglandin F(2alpha) and nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by ELISA and colorimetric assays at admission and 30 days following 72-h milrinone (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs-CRP and oxidative markers were significantly higher in patients on admission before inotropic treatment compared with controls (P<0.05). Short-term inotropic support improved clinical status as assessed by NYHA classification and by the 6-min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs-CRP and markers of oxidation (P<0.05) at 30 days. The effects of milrinone and dobutamine were similar. In conclusion, our results demonstrate that patients with decompensated CHF have marked systemic inflammation and increased production of oxygen free radicals. Short-term inotropic support improves functional status and reduces indices of inflammation and oxidative stress in patients with decompensated CHF.
authors.affiliation: Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada, H1T 1C8.
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.forename: Anique
authors.initials: A
authors.lastname: Ducharme
authors.forename: Reda
authors.initials: R
authors.lastname: Ibrahim
authors.forename: Lucette
authors.initials: L
authors.lastname: Whittom
authors.forename: Joel
authors.initials: J
authors.lastname: Lavoie
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guertin
authors.forename: Normand
authors.initials: N
authors.lastname: Racine
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Guoying
authors.initials: G
authors.lastname: Yao
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D003124:Colorimetry; D016207:Cytokines / Q000097:blood*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D018450:Disease Progression; D004280:Dobutamine / Q000627:therapeutic use; D019040:E-Selectin / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000627:therapeutic use; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D002316:Cardiotonic Agents; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016207:Cytokines; D019040:E-Selectin; D020382:Interleukin-18; D015850:Interleukin-6; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; D004280:Dobutamine; D014443:Tyrosine; D002097:C-Reactive Protein; D015237:Dinoprost; D020105:Milrinone