ROLE OF BETA-ADRENERGIC-RECEPTOR DOWN-REGULATION IN THE PEAK EXERCISERESPONSE IN PATIENTS WITH HEART-FAILURE DUE TO IDIOPATHIC DILATED CARDIOMYOPATHY

The effect of beta-adrenergic receptor downregulation on peak exercise response in patients with heart failure has not been directly investi gated. Seventy-two patients with idiopathic dilated cardiomyopathy who had a mean ejection fraction of 23 +/- 1% (mean +/- SUM) and New York Heart Association class II or Ill symptoms were investigated. Subject s underwent maximal exercise testing on a bicycle or a treadmill, hemo dynamic assessment by right heart catheterization, and measurement of total beta-adrenergic receptor density by I-125-iodocyanopindolol bind ing performed in the right ventricular endomyocardial biopsy tissue an d in peripheral lymphocytes. Endomyocardial biopsy beta-adrenergic rec eptor density (Bmax) was markedly decreased (45 +/- 2 fmol/mg), and si gnificantly lower than lymphocytes Bmax (107 +/- 14 fmol/mg; p <0.05). By univariate analysis, ail exercise variables correlated significant ly with biopsy tissue Bmax but not with lymphocyte Bmax. Maximal exerc ise oxygen consumption (VO(2)max) yielded the highest correlation with Bmax (r = 0.61, p <0.001). By stepwise regression analysis, VO2 max, Delta heart rate x systolic blood pressure, and ejection fraction were all independently related to Bmax. Myocardial p-adrenergic receptor d ownregulation is likely to be partially responsible for the reduced ch ronotropic and inotropic responses to peak exercise in patients with m ild to moderate symptomatic heart failure due to idiopathic dilated ca rdiomyopathy.