Inhaled β-agonist does not modify sympathetic activity in patients with COPD

Helge Haarmann, Cordula Mohrlang, Uta Tschiesner, David B Rubin, Thore Bornemann, Karin Rüter, Slavtcho Bonev, Tobias Raupach, Gerd Hasenfuß, Stefan Andreas, Helge Haarmann, Cordula Mohrlang, Uta Tschiesner, David B Rubin, Thore Bornemann, Karin Rüter, Slavtcho Bonev, Tobias Raupach, Gerd Hasenfuß, Stefan Andreas

Abstract

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.

Trial registration: This study was registered with the European Clinical Trials Database (EudraCT No. 2011-001581-18) and ClinicalTrials.gov ( NCT01536587 ).

Figures

Figure 1
Figure 1
Effects of salmeterol on MSNA, heart rate, systolic and diastolic blood pressure. Displayed are means ± SD. SBP = systolic blood pressure; DBP = diastolic blood pressure. * = significant changes in paired t-test (p < 0.05). For further information see results and Table 2.
Figure 2
Figure 2
Scatter plot of change in norepinephrine against change in MSNA. Displayed are changes from visit 1 (week 0) to after salmeterol inhalation at visit 2 (week 4). (r = 0.72; p = 0.01; n = 11).

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