Effects of catecholamine-β-adrenoceptor-cAMP system on severe patients with heart failure

摘要

Objective To investigate the association between catecholamine-β-adrenoceptor (β-AR)-adenosine 3′, 5′-monophosphate (cAMP) system and long-term prognosis in patients with chronic heart failure (CHF). Methods The study population comprised 73 patients with CHF (EF:23% +-10%) with a mean follow-up of 3.8+-1.9 years. Plasma levels of norepinephrine (NE) were measured using high performance lipid chromatography, β-adrenergic receptor density (Bmax) and the content of cAMP in peripheral lymphocytes were calculated using ~3H-dihydroalpneolo as ligand and competitive immunoassay, respectively. Deaths due to cardiovascular events within the follow-up period were registered. Results The total mortality was 64.7%, 57.4% of which was for cardiogenic (worsening heart failure; 32.4%; sudden death; 25.0%). In the cardiogenic death group, plasma levels of NE and epinephrine (E) (3.74 nmol/L +-0.09 nmol/L and 3.17 nmol/L +-1. Onmol/L) and the contents of peripheral lymphocyte cAMP (3.64 pmol/mg protein +-1.4 pmol/mg protein) were significantly increased as compared with the survival group (2.68 nmol/L +-0.07 nmol/L, 2.41 nmol/L +-0.24 nmol/L and 2.73 pmol/mg protein +-0.9 pmol/mg protein, respectively, all P<0.01). In the sudden death group, plasma levels of NE and E (5.01 nmol/L +-0.06 nmol/L and 4.13 nmol/L +-0.08 nmol/L) were significantly increased as compared with the worsening heart failure group (2.49 nmol/ L +-0.07 nmol/L and 2.33 nmol/L +-0.8 nmol/L, all P<0.001) and to the survival group (2.68 nmol/L +-0.07 nmol/L and 2.41 nmol/L +-0.14 nmol/L, all P<0.01). The incidences of sudden death were 0% , 75%, and 100% (χ~2 =16. 018, P<0.01) in patients with plasma NE <2.5 nmol/L, NE 2.5 nmol/L -4.5 nmol/L, and NE >4.5 nmol/L, respectively. In the worsening heart failure group, the content of peripheral lymphocyte cAMP (4.46 pmol/mg protein +-0.18 pmol/mg protein) was significantly increased compared with the sudden death group (2. 39 pmol/g protein +-0.9 pmol/mg protein, P<0.001) and to the survival group (2.73 pmol/mg protein +-1.1 pmol/mg protein, P< 0.001). The worsening heart failure death occurences were 5.0%, 72.2%, and 100% (χ~2 =14.26, P<0.01) in patients with a content of peripheral lymphocyte cAMP <2.5 nmol/L, cAMP 2.5 nmol/L -4.5 nmol/L, and cAMP > 4.5 nmol/L, respectively. B_(max) in peripheral lymphocyte was not significantly different (P>0.05) among the sudden death, worsening heart failure, and survival groups in CHF patients. Conclusions Plasma levels of catecholamine increase significantly, and B_(max) and the contents of cAMP in peripheral lymphocytes decrease significantly in patients with CHF. High plasma catecholamine levels may be associated with sudden death, and high intralymphocyte cAMP content may be associated with worsening heart failure in CHF patients.