Effect of digitalis on norepinephrine kinetics in congestive heart failure.
OBJECTIVE
The aim of this study was to test the hypothesis that digitalis glycosides would reduce sympathetic activity as reflected by forearm venous norepinephrine kinetics in patients with congestive heart failure.


BACKGROUND
Digitalis glycosides have been reported to decrease sympathetic nervous system activity with baroreceptor sensitization in experimental animals. Such effects could be of therapeutic importance in congestive heart failure.


METHODS
Double-blind randomized assessment was made of the effects of low dose intravenous deslanoside (Cedilanid-D, 0.002 mg/kg body weight) and vehicle on heart rate, arterial pressure, forearm blood flow, plasma norepinephrine, norepinephrine clearance and norepinephrine spillover in nine patients with stable congestive heart failure, New York Heart Association functional class II or III. Open label assessment of the responses to 0.6 mg of deslanoside was made in an overlapping group of seven patients. All measurements were made 30 and 60 min after intravenous injection of drug or vehicle and after 15 min of 30 degrees head-down tilt as a test of the sympathetic response to baroreceptor loading.


RESULTS
Heart rate, arterial pressure and forearm blood flow were unchanged by low dose deslanoside. Heart rate decreased slightly with the 0.6 mg dose with the patients in the supine position. Norepinephrine spillover and clearance decreased with time on each study day in the supine position, but no effect was attributable to digitalis. Plasma norepinephrine and norepinephrine clearance and spillover all remained unchanged during head-down tilt on each study day.


CONCLUSIONS
Nonpressor doses of deslanoside do not suppress sympathetic activity as reflected by venous norepinephrine and norepinephrine spillover in patients with congestive heart failure. Further, deslanoside did not normalize the sympathetic response to mild baroreceptor loading produced by head-down tilt. These data do not support sympathoinhibition through baroreceptor sensitization as a likely effect of digitalis in congestive heart failure.
Goldsmith
S R
SR
Hennepin County Medical Center, Minneapolis, Minnesota 55415.
Simon
A B
AB
Miller
E
E
D003892:Deslanoside / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011187:Posture / Q000502:physiology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D009638:Norepinephrine; D003892:Deslanoside