Effects of chronic clonidine administration on sympathetic nerve traffic and baroreflex function in heart failure.
Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0+/-1.1 years (mean+/-SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (-46.8% and -26.7%, respectively; P<0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested.
Grassi
G
G
Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza (Milan), Italy.
Turri
C
C
Seravalle
G
G
Bertinieri
G
G
Pierini
A
A
Mancia
G
G
D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology*
D013565:Sympatholytics; D009599:Nitroprusside; D010656:Phenylephrine; D003000:Clonidine; D009638:Norepinephrine