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: Michel White, Anique Ducharme, Reda Ibrahim, Lucette Whittom, Joel Lavoie, Marie-Claude Guertin, Normand Racine, Ying He, Guoying Yao, Jean L Rouleau, Ernesto L Schiffrin, Rhian M Touyz
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 110 Issue 4 Pg. 483-9 (Apr 2006) ISSN: 0143-5221 [Print] England
• PMID: 16402915 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, blood)
• Disease Progression
• Dobutamine (therapeutic use)
• E-Selectin (blood)
• Enzyme-Linked Immunosorbent Assay
• Exercise Test
• Female
• Heart Failure (drug therapy, immunology, 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, blood)