Firing probability and mean firing rates of human muscle vasoconstrictor neurones are elevated during chronic asphyxia

Abstract

Elevated muscle sympathetic nerve activity (MSNA) features in many cardiovascular diseases, but how this sympathoexcitation is brought about differs across pathologies. Unitary recordings from post-ganglionic muscle vasoconstrictor neurones in human subjects have shown that the augmented MSNA in the obstructive sleep apnoea syndrome (OSAS) is associated with an increase in firing probability and mean firing rate, and an increase in multiple within-burst firing. Here we characterize the firing properties of muscle vasoconstrictor neurones in patients with chronic obstructive pulmonary disease (COPD), who are chronically asphyxic. We tested the hypothesis that this elevated chemical drive would shift the firing pattern from that seen in healthy subjects to that seen in OSAS. The mean firing probability (52%) and mean firing rate (0.92 Hz) of 17 muscle vasoconstrictor neurones recorded in COPD were comparable to those previously recorded in OSAS (51% and 0.96 Hz), but significantly higher than those recorded in a group of healthy subjects with high levels of resting MSNA (35% and 0.33 Hz). In COPD single neurones fired once in 63% of cardiac intervals, comparable to OSAS (59%), but significantly lower than in the healthy group (78%). Conversely, single neurones fired twice in 25% of cardiac intervals, similar to OSAS (27%), but significantly higher than in the healthy group (18%). We conclude that the chronic asphyxia associated with COPD results in an increase in the firing probability and mean firing frequency of muscle vasoconstrictor neurones and causes a shift towards multiple firing, reflecting an increase in central muscle vasoconstrictor drive.

Figure 1

Multi-unit recording from a muscle fascicle of the common peroneal nerve in an awake female patient with COPD, showing a high incidence of muscle sympathetic nerve activity. Sympathetic bursts occurred in almost every cardiac interval in this patient.

Figure 2

Unitary recording from a single muscle vasoconstrictor neurone (negative-going spikes) in an awake male patient with COPD. This unit generally fired only one spike (indicated by asterisks) per cardiac interval, but occasionally fired multiple spikes per cardiac interval. A spontaneously active muscle spindle (positive-going spikes) can be seen in the background. Because the sympathetic recording was so focal in this case, the RMS nerve signal does not adequately represent the population discharge.

Figure 3

Cross-correlation histograms between unit firing and ECG, and autocorrelation histograms for ECG. Data from three units recorded in COPD (A–C) and one unit recorded in bronchiectasis (D). n= number of spikes comprising the histogram.

Figure 4

Single-unit data from 17 muscle vasoconstrictor neurones recorded in chronic obstructive pulmonary disease (COPD) and from 6 neurones recorded in bronchiectasis (BE). Histograms showing pooled data on the percentage of cardiac intervals (mean ±s.e.m.) in which units were quiescent, fired a single spike or multiple spikes. In the top panels, all cardiac intervals have been included: the open columns represent those cardiac intervals in which the neurones were quiescent. The lower panels show data in which only those cardiac intervals were included in which a unit was active.