Inhaled β-agonist does not modify sympathetic activity in patients with COPD.
BACKGROUND
Neurohumoral activation is present in COPD and might provide a link between pulmonary and systemic effects, especially cardiovascular disease. Because long acting inhaled β-agonists reduce hyperinflation, they could reduce sympathoexcitation by improving the inflation reflex. We aimed to evaluate if inhaled therapy with salmeterol reduces muscle sympathetic nerve activity (MSNA) evaluated by microneurography.


METHODS
MSNA, heart rate, blood pressure, and respiration were continually measured. After baseline recording of 20 minutes, placebo was administered; after further 45 minutes salmeterol (50 μg) was administered which was followed by a further 45 minutes of data recording. Additionally, lung function, plasma catecholamine levels, arterial pulse wave velocity, heart rate variability, and baroreflex sensitivity were evaluated. Following 4 weeks of treatment with salmeterol 50 μg twice daily, measurements were repeated without placebo administration.


RESULTS
A total of 32 COPD patients were included. Valid MSNA signals were obtained from 18 patients. Change in MSNA (bursts/100 heart beats) following acute administration of salmeterol did not differ significantly from the change following placebo (-1.96 ± 9.81 vs. -0.65 ± 9.07; p = 0.51) although hyperinflation was significantly reduced. Likewise, no changes in MSNA or catecholamines were observed after 4 weeks. Heart rate increased significantly by 3.8 ± 4.2 (p < 0.01) acutely and 3.9 ± 4.3 bpm (p < 0.01) after 4 weeks. Salmeterol treatment was safe and well tolerated.


CONCLUSIONS
By using microneurography as a gold standard to evaluate sympathetic activity we found no change in MSNA following salmeterol inhalation. Thus, despite an attenuation of hyperinflation, the long acting β-agonist salmeterol does not appear to reduce nor incite sympathoexcitation.


BACKGROUND
This study was registered with the European Clinical Trials Database (EudraCT No. 2011-001581-18) and ClinicalTrials.gov ( NCT01536587 ).
Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. helge.haarmann@med.uni-goettingen.de.
Helge
H
Haarmann
GlaxoSmithKline (GSK), Munich, Germany. cordula.c.mohrlang@gsk.com.
Cordula
C
Mohrlang
GlaxoSmithKline (GSK), Munich, Germany. uta.u.tschiesner@gsk.com.
Uta
U
Tschiesner
GlaxoSmithKline, Research Triangle Park, NC, USA. david.b.rubin@gsk.com.
David B
DB
Rubin
Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. thore@gmx.org.
Thore
T
Bornemann
Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. karin.rueter@med.uni-goettingen.de.
Karin
K
Rüter
Mannheim Biomedical Engineering Laboratories, Medical Faculty at Heidelberg University, Mannheim, Germany. slavtcho.bonev@mabel.info.
Slavtcho
S
Bonev
Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. raupach@med.uni-goettingen.de.
Tobias
T
Raupach
Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. hasenfus@med.uni-goettingen.de.
Gerd
G
Hasenfuß
Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. sandreas@lungenfachklinik-immenhausen.de.|Lung Clinic Immenhausen, Immenhausen, Krs. Kassel, Germany. sandreas@lungenfachklinik-immenhausen.de.
Stefan
S
Andreas
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010543:Peroneal Nerve / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D063177:Pulse Wave Analysis; D012129:Respiratory Function Tests; D056152:Respiratory Rate / Q000187:drug effects; D000068299:Salmeterol Xinafoate / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D019208:Brain-Derived Neurotrophic Factor; D002395:Catecholamines; D000068299:Salmeterol Xinafoate; C579455:BDNF protein, human; D009638:Norepinephrine; D004837:Epinephrine