Chronic obstructive pulmonary disease-induced autonomic dysfunction may be associated with cerebral blood flow regulation and brain function.

Abstract

Chronic obstructive pulmonary disease (COPD) increases the risk of cerebrovascular disease and brain dysfunction, such as ischaemic stroke and dementia, in proportion to its severity. Cerebral blood flow (CBF) regulation may be a key factor for this phenomenon, but the physiological mechanisms of COPD pathogenesis regarding cerebrovascular disease are yet to be established. Physiologically, COPD is a chronic hypoxic condition, and long-term oxygen therapy improves survival in patients with COPD and severe resting hypoxaemia. Given this background, Hoiland et al. (2018) have reported, in this issue of Experimental Physiology, the effects of oxygen therapy on cerebral oxygen delivery and neurovascular function in patients with COPD. The authors demonstrated that oxygen therapy improved cerebral oxygen delivery by increasing peripheral oxyhaemoglobin saturation () and enhanced neurovascular function in patients with COPD. These findings suggested that such oxygen delivery and functional neurovascular improvements may provide a physiological link between oxygen therapy and the reduced risk of cerebrovascular disease in patients with COPD. Thus, oxygen therapy appears beneficial for patients with COPD. On the contrary, oxygen therapy did not alter volumetric global CBF (Hoiland et al., 2018), suggesting that the cerebral vasculature has a low sensitivity to the acute normalization of . From these results, it can be suspected that the contribution of CBF regulation to COPD-induced cerebrovascular disease or brain dysfunction is likely to be minimal. In patients with COPD receiving oxygen therapy, we should consider cerebral oxygen delivery and cerebral haemodynamics and other physiological mechanisms potentially induced by hypoxaemia to understand the physiological mechanisms of this positive phenomenon. One example includes autonomic dysfunction, which is commonly observed in patients with COPD. Indeed, a previous study (van Gestel, Kohler, & Clarenbach, 2012) has demonstrated that autonomic dysfunction through sympathetic nervous system overactivity might contribute to the initiation and progression of cardiovascular disease in the examined population. However, the contributions of autonomic dysfunction to COPD-induced cerebrovascular disease and brain dysfunction may not be simple, because autonomic dysfunction modifies cerebral vasculature regulation (cerebral autoregulation and cerebral CO2 reactivity), the arterial baroreflex and the respiratory system (Ogoh & Ainslie, 2009). Indeed, baroreflex function is attenuated in patients with COPD. Importantly, the baroreflex simultaneously influences the respiratory system (ventilation and tidal volume) and the control of arterial pressure (Brunner, Sussman, Greene, Kallman, & Shoukas, 1982). Moreover, there is an interaction between cerebral vasculature regulation and the arterial baroreflex or respiratory system (Ogoh & Ainslie, 2009). Taken together, we cannot rule out the possibility that autonomic dysfunction might affect cerebral vasculature and function in the examined population both directly and indirectly. Indeed, another study (Bartels, Gonzalez, Kim, & De Meersman, 2000) demonstrated that oxygen therapy increased baroreflex sensitivity in patients with COPD, indicating that oxygen supplementation in this population significantly and favourably altered autonomic activity. Thus, oxygen therapy-modified autonomic function may be associated with improved survival in patients with COPD. Regarding this concept, the duration or severity of COPD may cause different functional autonomic adaptations and may result in different effects of oxygen therapy on the cerebral vasculature. The work of Hoiland et al. (2018) has clearly described the mechanisms through which oxygen therapy improved survival in patients with COPD. However, in order to identify the mechanisms underlying these effects, we should conduct additional, detailed investigations of the physiological regulatory mechanisms associated with various autonomic functions.