Altered cardiovascular autonomic regulation after 2-week inhaled salbutamol treatment in asthmatic children.
We studied the effects of therapeutic 2-week inhaled salbutamol treatment on the cardiovascular and respiratory autonomic nervous regulation in eight children with asthma. In this randomized, double-blind, placebo-controlled crossover study our test subjects inhaled 200 microg salbutamol or placebo thrice daily for 14 days. After the 14-day treatment we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline and the response to a single 600 microg salbutamol inhalation. The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis. Two-week salbutamol treatment increased baseline low frequency (LF) variability (P < 0.05) and low frequency/high frequency (LF/HF) variability ratio of R-R intervals (P < 0.05) when compared to the placebo treatment. As a response to the single salbutamol inhalation the increase in LF/HF ratio of R-R intervals was smaller after the 2-week salbutamol treatment (P < 0.01). No significant differences were found in the bronchodilatory response after the treatment period.


CONCLUSIONS
Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. Because these effects were evident 18 h after cessation of the therapy they are likely to reflect the adaptation of organ responses to regular therapy or altered central autonomic regulation rather than direct drug effect. A slight tolerance developed in the sympathovagal cardiac response but not in the bronchodilatory response.
Jartti
T T
TT
Department of Paediatrics, Turku University Hospital, Finland.
Kaila
T J
TJ
Tahvanainen
K U
KU
Kuusela
T A
TA
Vanto
T T
TT
Välimäki
I A
IA
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000187:drug effects*; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D012129:Respiratory Function Tests; D013566:Sympathomimetics / Q000008:administration & dosage / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D013566:Sympathomimetics; D000420:Albuterol