Sympathetic overactivity in active ulcerative colitis: effects of clonidine.
Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LF(RR); normalized units) and high-frequency (HF) parasympathetic (HF(RR); normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LF(SAP)), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LF(RR), LF/HF, and LF(SAP) were higher and HF(RR) was lower in patients than in controls. Tilt decreased HF(RR) and increased MSNA and LF(RR) less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LF(RR), and increased HF(RR), whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.
Furlan
Raffaello
R
Unità Sincopi e Disturbi della Postura, Medicina Interna II, Ospedale L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, Italy. raffaello.furlan@unimi.it
Ardizzone
Sandro
S
Palazzolo
Laura
L
Rimoldi
Alexandra
A
Perego
Francesca
F
Barbic
Franca
F
Bevilacqua
Maurizio
M
Vago
Luca
L
Bianchi Porro
Gabriele
G
Malliani
Alberto
A
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*
D000316:Adrenergic alpha-Agonists; D003000:Clonidine