Tumour necrosis factor and inducible nitric oxide synthase in dilated cardiomyopathy.
BACKGROUND
Two important features of dilated cardiomyopathy (DCM) are low myocardial contractility and risk of thromboembolism. Nitric oxide (NO) exerts a negative inotropic effect on the myocardium and is produced by NO-synthase, an inducible form of which (iNOS) is stimulated by tumour necrosis factor (TNF-alpha). Accordingly, we hypothesized that locally produced TNF-alpha might contribute to the pathogenesis and complications of DCM by inducing iNOS in the heart.


METHODS
iNOS and TNF-alpha were quantified by histochemistry and computerised image analysis in explanted heart tissues or myocardial biopsy material from patients with DCM (n = 21) or ischaemic heart disease (HD; n = 10) and from normal donor hearts (n = 9).


RESULTS
Immunoreactivity for iNOS was strong in myocytes of DCM hearts, particularly in areas adjacent to the endocardium, and moderately intense in blood vessels of DCM and IHD hearts. The median optical density of the immunostaining for iNOS was greater in cardiac myocytes of patients with DCM (0.86, range 0.21 to 1.29) than in those from patients with IHD (0.20, range 0.095 to 0.26) (p < 0.01) or controls (0.01, range 0.001 to 0.02) (p < 0.001). Staining for TNF-alpha was observed in the vascular endothelium and smooth muscle cells of patients with DCM but not in IHD or control tissues.


CONCLUSIONS
The localisation of iNOS and TNF-alpha within cardiac tissues in DCM suggests that TNF-alpha contributes to both the low contractility and the tendency to thromboembolism in these patients.
Habib
F M
FM
Department of Cardiology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Springall
D R
DR
Davies
G J
GJ
Oakley
C M
CM
Yacoub
M H
MH
Polak
J M
JM
D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000503:physiopathology; D003327:Coronary Disease / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide