High plasma levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8) characterize patients prone to ventricular fibrillation complicating myocardial infarction.
BACKGROUND
Atherosclerotic plaques prone to cause thrombotic complications and plaque rupture account for the majority of fatal myocardial infarctions (MI), which may be complicated by ventricular fibrillation (VF). Matrix-degrading metalloproteinases (MMPs) and their inhibitors (TIMPs) are expressed in atherosclerotic lesions and contribute to plaque vulnerability. Interleukin-8 (IL-8) is one of the predominant chemokines interacting with MMPs and TIMPs and the coagulation system. The aim of the present study was to assess potential differences of levels of MMP-9, TIMP-1 and IL-8 in postmyocardial infarction patients with or without VF complicating acute MI.


METHODS
Blood samples were taken from 45 patients with VF complicating acute MI and from 88 patients without VF. All samples were collected during a symptom-free interval remote from the acute ischemic event with a median of 556 days. The markers of interest were TIMP-1, MMP-9 and IL-8.


RESULTS
IL-8 and TIMP-1 levels were significantly higher among patients with VF than among patients without VF (p<0.001). In a logistic regression approach IL-8 was an independent indicator of patients prone to VF during MI (p=0.03). High levels of TIMP-1 (p=0.05), MMP-9 (p=0.03), the MMP-9/TIMP-1 ratio (p=0.049) and hypertension (p=0.02) were found to be indicators in patients with reinfarction or unstable angina pectoris during follow-up. Hypertension (p=0.02) and MMP-9 (p=0.03) were the only significant indicators characterizing patients undergoing coronary reinterventions, such as percutaneous coronary interventions and coronary bypass surgery.


CONCLUSIONS
Higher TIMP-1 and IL-8 levels are present in patients with VF complicating MI. High TIMP-levels may be related to the degree of fibrosis which is a substrate for electrical instability and may contribute to the occurrence of VF. Patients prone to develop VF during MI seem to have an increased proinflammatory condition compared to patients without VF.
Elmas
Elif
E
1st Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany. elif.elmas@med.ma.uni-heidelberg.de
Lang
Siegfried
S
Dempfle
Carl Erik
CE
Kälsch
Thorsten
T
Hannak
Dieter
D
Sueselbeck
Tim
T
Wolpert
Christian
C
Borggrefe
Martin
M
Brueckmann
Martina
M
D000368:Aged; D015415:Biomarkers / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000473:pathology; D016209:Interleukin-8 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000473:pathology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014693:Ventricular Fibrillation / Q000097:blood* / Q000150:complications / Q000473:pathology
D015415:Biomarkers; D016209:Interleukin-8; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9