TUMOR-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 prod uced by NO-synthase, an inducible form of which (iNOS) is stimulated b y tumour necrosis factor (TNF-alpha). Accordingly, we hypothesised tha t locally produced TNF-alpha might contribute to the pathogenesis and complications of DCM by inducing iNOS in the heart. Methods iNOS and T NF-alpha were quantified by histochemistry and computerised image anal ysis in explanted heart tissues or myocardial biopsy material from pat ients with DCM (n=21) or ischaemic heart disease (IHD; n=10) and from normal donor hearts (n=9). Findings Immunoreactivity for iNOS was stro ng in myocytes of DCM hearts, particularly in areas adjacent to the en docardium, and moderately intense in blood vessels of DCM and IHD hear ts, The median optical density of the immunostaining for iNOS was grea ter 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 c ells of patients with DCM but not in IHD or control tissues. Interpret ation 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.