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 affe cted by clonidine is unknown. In 26 normotensive patients age 58.0 +/-1.1 y ears (mean +/- SEM) affected by congestive heart failure (New York Heart As sociation functional class II or III) and treated with furosemide and enala pril, we measured mean arterial pressure, heart rate, venous plasma norepin ephrine, and muscle sympathetic nerve traffic (microneurography) at rest an d during baroreceptor stimulation and deactivation caused by stepwise intra venous infusions of phenylephrine and nitroprusside, respectively. Measurem ents were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, r andomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity a nd echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were sig nificantly 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 fai lure patients who are undergoing conventional drug treatment, chronic cloni dine administration exerts marked sympathoinhibitory effects without advers ely affecting cardiac functions and clinical state. Whether this leads to f urther therapeutic benefits remains to be tested.