The failing human heart does not release nitrogen oxides

It has been suggested that the myocardial production of nitric oxide, as a consequence of expression of the inducible isoform of nitric oxide synthase (NOS), plays an important role in the pathophysiology of heart failure. We determined the net cardiac production of nitrogen oxides (NOx), as a measure of NOS activity, by performing arterial and coronary sinus sampling in healthy control subjects (n=6) and patients with end-stage heart failure (n=10). The arterial plasma NOx concentration was significantly elevated in heart failure patients (58.4+/-7.0 vs 36.9+/-4.9 mu M, p<0.05). However, we found net extraction of NOx across the heart, with no difference between the two groups. Therefore, the heart does not appear to be a source of NOx in heart failure, and this study does not support a pathophysiological role for NOx in this condition.