Sympathetic inhibition with clonidine improves autonomic balance in congestive heart failure

In this double-blind, placebo-controlled crossover study, we examined the effect of transdermal clonidine (given for 5 days) on autonomic control in 14 patients with mild to moderate congestive heart failure by heart rate variability analysis. Compared with placebo, clonidine increased the 24-h mean R-R interval from 718+/-110 to 811+/-117 ms (P<0.01), increased the S.D. of all normal RR intervals (SDNN) from 60.8+/-18.5 to 80.9+/-21.4 ms (P<0.01), the S.D. of the average RR intervals for all 5-min segments (SDANN) from 54.7+/-15.2 to 70.5+/-18.4 ms (P<0.01) and the mean of the S.D.s of all RR intervals for all 5-min segments (SDNN index) from 29.2+/-8.3 to 36.5+/-8.1 ms (P<0.01). The root mean square successive differences (r-MSSD) and the percent of differences between adjacent RR intervals >50 ms (pNN50) were also increased from 18.3+/-6.7 to 23.1+/-7.0 ms (P<0.01) and from 2.1+/-1.9 to 4.5+/-3.0% (P<0.01). In addition, total power, low frequency power and high frequency power were increased from 641+/-322 to 898+/-403 ms2/Hz (P<0.01), from 149+/-97 to 216+/-133 ms2/Hz (P<0.01) and from 52.8+/-27.1 to 93.2+/-41.3 ms2/Hz (P<0.01), respectively. The plasma norepinephrine level was decreased significantly from 0.52+/-0.18 to 0.24+/-0.09 ng/ml (P<0.01) after clonidine therapy. Changes in heart rate variability measures after clonidine administration were positively related to changes in plasma norepinephrine level. These results indicate that suppressing the sympathetic nervous system by clonidine improves autonomic balance in patients with congestive heart failure. But whether such restoration of the autonomic control has a beneficial effect on the long-term management of these patients still needs further investigation.