Enhanced proinflammatory response of mononuclear cells to in vitro LPS-challenge in patients with ventricular fibrillation in the setting of acute myocardial infarction.
OBJECTIVE
Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death. A potential role of intrinsic, subclinical inflammatory states in patients suffering from ischemia-related VF has not been investigated yet. The aim of the present study was (i) to examine serum levels of proinflammatory markers in VF survivors and (ii) to evaluate basal and lipopolysaccharide (LPS)-stimulated interleukin-8-mRNA (IL-8-mRNA) levels in patients with and without VF complicating AMI.


METHODS
Twenty-five patients with a history of VF during AMI and a control group of 25 AMI patients without VF were included. Blood samples were taken remote from AMI with a mean of 590 days. Circulating serum levels of IL-8, IL-6, soluble E-selectin (sE-selectin), tissue factor activity (TFA), tissue inhibitor of matrix-metalloproteinase-1 (TIMP-1) and matrix-metalloproteinase-9 (MMP-9) were measured. Mononuclear cells were isolated by density gradient centrifugation. The cells were stimulated with lipopolysaccharide (LPS) from Escherichia coli (700 ng/mL). IL-8-mRNA levels in mononuclear cells were determined by a colorimetric mRNA quantification assay.


RESULTS
Serum levels (median; range) of IL-8 (VF: 2.24 pg/mL; <0.10-19.3 pg/mL versus controls: 0.10 pg/mL; <0.10-7.7 pg/mL; p=0.014), IL-6 (VF: 0.68 pg/mL; <0.05-2.9 pg/mL versus controls: 0.23 pg/mL; <0.05-1.8 pg/mL; p=0.042) and TIMP-1 (VF: 229 ng/mL; 144-348 ng/mL versus controls: 186 ng/mL; 126-263 ng/mL; p=0.014) were significantly higher among patients with VF as compared to controls. Baseline IL-8-mRNA concentrations of blood mononuclear cells were significantly higher among patients with VF (257 amol/mL; 52-2672 amol/mL) as compared to patients without VF (37 amol/mL, 3.2-770 amol/mL; p<0.01). IL-8-mRNA levels after LPS-challenge were significantly higher among patients with VF (3503 amol/mL; 215-13,573 amol/mL) than in patients without VF (1003 amol/mL; 208-3386 amol/mL; p<0.01).


CONCLUSIONS
Circulating IL-8, IL-6, and TIMP-1 concentrations as well as IL-8-mRNA expression in mononuclear cells at baseline and after LPS-challenge are increased among patients with a history of VF in the setting of AMI as compared to patients without VF. These findings indicate an enhanced inflammatory response to a proinflammatory stimulus in VF survivors. The magnitude of this increased acute phase reactants may indicate a novel pathway of arrhythmogenesis in patients with AMI.
University Hospital of Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Department of Medicine, Cardiology, Angiology, Pneumology, Intensive Care Medicine, D-68167 Mannheim, Germany. elif.elmas@med.ma.uni-heidelberg.de
Elif
E
Elmas
Lena
L
Hölzer
Siegfried
S
Lang
Tatjana
T
Popp
Thorsten
T
Kälsch
Christian
C
Wolpert
Martina
M
Brueckmann
Martin
M
Borggrefe
D002478:Cells, Cultured; D002633:Chemotaxis; D016207:Cytokines / Q000097:blood / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000150:complications* / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D008070:Lipopolysaccharides