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 hea rt failure, but myocardial cAMP content has not yet been evaluated in heart failure patients in comparison with controls. We therefore measu red the myocardial content of cAMP by radioimmunossay in endomyocardia l biopsies from patients in different stages of heart failure and in c ontrols 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 affect ed by heart failure. Myocardial cAMP (in fmol.mu g(-1) non-collagen pr otein) 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 p g.mu g(-1) non-collagen protein) in the same biopsies was significantl y reduced in heart failure (4.0 +/- 3.0) in comparison with the same c ontrols (11.5 +/- 3.0, P (0.0002). Plasma cAMP in 20 heart failure pat ients (22 0 i 4 2 pmoll(-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 lev els are indistinguishable from controls in human heart failure and the refore do not contribute to a further characterization of the cardiac adrenergic system in these patients. This is most likely due to the im possibility of obtaining biopsies with bury unstimulated adenylyl cycl ase activity.