Sympathetic and Vagal Nerve Activity in COPD: Pathophysiology, Presumed Determinants and Underappreciated Therapeutic Potential.

Abstract

This article explains the comprehensive state of the art assessment of sympathetic (SNA) and vagal nerve activity recordings in humans and highlights the precise mechanisms mediating increased SNA and its corresponding presumed clinical determinants and therapeutic potential in the context of chronic obstructive pulmonary disease (COPD). It is known that patients with COPD exhibit increased muscle sympathetic nerve activity (MSNA), as measured directly using intraneural microelectrodes-the gold standard for evaluation of sympathetic outflow. However, the underlying physiological mechanisms responsible for the sympathoexcitation in COPD and its clinical relevance are less well understood. This may be related to the absence of a systematic approach to measure the increase in sympathetic activity and the lack of a comprehensive approach to assess the underlying mechanisms by which MSNA increases. The nature of sympathoexcitation can be dissected by distinguishing the heart rate increasing properties (heart rate and blood pressure variability) from the vasoconstrictive drive to the peripheral vasculature (measurement of catecholamines and MSNA) (Graphical Abstract Figure 1). Invasive assessment of MSNA to the point of single unit recordings with analysis of single postganglionic sympathetic firing, and hence SNA drive to the peripheral vasculature, is the gold standard for quantification of SNA in humans but is only available in a few centres worldwide because it is costly, time consuming and requires a high level of training. A broad picture of the underlying pathophysiological determinants of the increase in sympathetic outflow in COPD can only be determined if a combination of these tools are used. Various factors potentially determine SNA in COPD (Graphical Abstract Figure 1): Obstructive sleep apnoea (OSA) is highly prevalent in COPD, and leads to repeated bouts of upper airway obstructions with hypoxemia, causing repetitive arousals. This probably produces ongoing sympathoexcitation in the awake state, likely in the "blue bloater" phenotype, resulting in persistent vasoconstriction. Other variables likely describe a subset of COPD patients with increase of sympathetic drive to the heart, clinically likely in the "pink puffer" phenotype. Pharmacological treatment options of increased SNA in COPD could comprise beta blocker therapy. However, as opposed to systolic heart failure a similar beneficial effect of beta blocker therapy in COPD patients has not been shown. The point is made that although MSNA is undoubtedly increased in COPD (probably independently from concomitant cardiovascular disease), studies designed to determine clinical improvements during specific treatment will only be successful if they include adequate patient selection and translational state of the art assessment of SNA. This would ideally include intraneural recordings of MSNA and-as a future perspective-vagal nerve activity all of which should ideally be assessed both in the upright and in the supine position to also determine baroreflex function.