Myocardial cyclic AMP and norepinephrine content in human heart failure

Impaired production of myocardial cyclic adenosine monophosphate (cAMP) is thought to contribute to contractile dysfunction in end stage heart failure, but myocardial cAMP content has not yet been evaluated in heart failure patients in comparison with controls. We therefore measured the myocardial content of cAMP by radioimmunoassay in endomyocardial biopsies from patients in different stages of heart failure and in controls and correlated it with biochemical and functional parameters. The myocardial content of norepinephrine was determined by HPLC in the same biopsies in order to assess if the myocardium studied was affected by heart failure. Myocardial cAMP (in fmol.microgram-1 non-collagen protein) in 20 patients with heart failure (LVEF: 27 +/- 8%, cAMP: 5.8 +/- 2.0) was unchanged in comparison with eight controls (LVEF: 64 +/- 4.7%, cAMP, 4.9 +/- 2.1). In contrast, myocardial norepinephrine (in pg.microgram-1 non-collagen protein) in the same biopsies was significantly reduced in heart failure (4.0 +/- 3.0) in comparison with the same controls (11.5 +/- 3.0, P < 0.0002). Plasma cAMP in 20 heart failure patients (22.0 +/- 4.2 pmol.l-1) was not different from controls(22.0 +/- 7.8), whereas plasma norepinephrine was increased (heart failure: 460 +/- 257 pg.ml-1, controls 182 +/- 49, P < 0.001). Myocardial cAMP levels are indistinguishable from controls in human heart failure and therefore do not contribute to a further characterization of the cardiac adrenergic system in these patients. This is most likely due to the impossibility of obtaining biopsies with truly unstimulated adenylyl cyclase activity.