Augmented sympathetic neural response to simulated obstructive apnoea in human heart failure

Abstract

Sleep apnoea in heart failure increases mortality risk, possibly as a result of greater activation of the sympathetic nervous system. In healthy subjects, simulated central apnoeas (holding breath) and obstructive apnoeas (Mueller manoeuvres) increase muscle sympathetic activity equally, primarily through chemoreceptor stimulation. In heart failure, however, Mueller manoeuvres cause greater reductions in blood pressure than breath holds. We hypothesized that in heart failure, the summation of arterial baroreceptor unloading and chemoreceptor stimulation would increase sympathetic activity more during obstructive than central apnoeas. Healthy human subjects and heart failure patients (seven of each) performed 15-s breath holds and 15-s Mueller manoeuvres. Breath holds evoked a progressive increase in muscle sympathetic nerve activity in both groups, but had no effect on blood pressure. In healthy subjects, breath holds and Mueller manoeuvres caused equal peaks in sympathetic activity. In contrast, in heart failure patients, Mueller manoeuvres caused a progressive decrease in blood pressure (P<0.05) and greater increases in sympathetic activity than breath holds (P<0.01). In heart failure, simulated obstructive apnoea elicits greater increases in sympathetic activity than simulated central apnoea, due to its additional hypotensive effect. These present findings offer novel insight into the potential role of sleep apnoea in augmenting sympathetic activity and accelerating disease progression in heart failure.