Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support

Clin Sci (Lond). 2006 Apr;110(4):483-9. doi: 10.1042/CS20050317.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cardiotonic Agents / therapeutic use*
  • Case-Control Studies
  • Cell Adhesion Molecules / blood
  • Chemokine CCL2 / blood
  • Colorimetry
  • Cytokines / blood*
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Disease Progression
  • Dobutamine / therapeutic use
  • E-Selectin / blood
  • Enzyme-Linked Immunosorbent Assay
  • Exercise Test
  • Female
  • Heart Failure / drug therapy
  • Heart Failure / immunology*
  • Heart Failure / metabolism
  • Humans
  • Inflammation
  • Interleukin-18 / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Milrinone / therapeutic use
  • Oxidative Stress
  • Thiobarbituric Acid Reactive Substances / analysis
  • Tyrosine / analogs & derivatives
  • Tyrosine / blood

Substances

  • Biomarkers
  • CCL2 protein, human
  • Cardiotonic Agents
  • Cell Adhesion Molecules
  • Chemokine CCL2
  • Cytokines
  • E-Selectin
  • Interleukin-18
  • Interleukin-6
  • Thiobarbituric Acid Reactive Substances
  • 8-epi-prostaglandin F2alpha
  • 3-nitrotyrosine
  • Dobutamine
  • Tyrosine
  • C-Reactive Protein
  • Dinoprost
  • Milrinone