Acute effects of beta 1-selective and nonselective beta-adrenergic receptor blockade on cardiac sympathetic activity in congestive heart failure.
BACKGROUND
beta-Blockers may reduce cardiac sympathetic activity in patients with heart failure by antagonizing beta-adrenergic receptors that facilitate sympathetic outflow to the heart. To explore this possible effect of beta-blockade, we measured cardiac norepinephrine spillover responses in patients with heart failure after the acute administration of either propranolol, a nonselective beta-blocker, or metoprolol, a beta 1-selective agent.


RESULTS
Eighteen patients were studied. Repeated intravenous doses of propranolol (0.5 mg; nine patients; left ventricular ejection fraction, 14 +/- 2%) or metoprolol (1.0 mg; nine patients; left ventricular ejection fraction, 18 +/- 2%) were administered until one of the following end points was reached: a 15% decrease in heart rate, left ventricular +dP/dt, or mean arterial blood pressure or a 5 mm Hg increase in left ventricular end-diastolic pressure. Propranolol (mean dose, 2.0 mg) and metoprolol (mean dose, 3.6 mg) caused similar reductions in heart rate, +dP/dt, and coronary sinus plasma flow. Cardiac norepinephrine spillover was reduced after propranolol (277 +/- 55 to 262 +/- 53 pmol/min, P < .05) but was increased after metoprolol (233 +/- 57 to 296 +/- 82 pmol/min, P < .05). In a comparison of the two groups, the decrease in spillover after propranolol was significantly different than the increase seen after metoprolol (P < .01).


CONCLUSIONS
The administration of a beta 1-selective antagonist was associated with increased cardiac norepinephrine spillover. In contrast, the administration of a nonselective beta-blocker until similar hemodynamic end points were reached caused a reduction in norepinephrine spillover. This suggests that in patients with heart failure, nonselective beta-blockade may have favorable inhibitory effects on cardiac sympathetic activity.
Newton
G E
GE
Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Parker
J D
JD
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D004837:Epinephrine / Q000097:blood; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D008790:Metoprolol; D009638:Norepinephrine; D004837:Epinephrine