Pathological sympathoexcitation: how is it achieved?

Abstract

Aim: Congestive heart failure (CHF) and obstructive sleep apnoea syndrome (OSAS) are both associated with an intense sympathoexcitation, including an increased muscle sympathetic nerve activity (MSNA). We have studied the firing characteristics of single vasoconstrictor fibres to the muscle vascular bed in CHF and OSAS patients, at rest and during transient sympathoexcitatory stimuli, to elucidate the mechanisms by which vasoconstrictor output is augmented in these conditions.

Results: The main alternatives for augmenting sympathetic output are an increased firing frequency of individual nerve fibres and an increased recruitment of nerve fibres. Starting with the frequency alternative, the inherent bursting character of MSNA provides two possibilities to increase the firing of individual fibres: (1) by increasing the proportion of neural bursts in which the fibre is active (increased firing probability) and (2) by increasing the number of spikes a fibre generates per burst (increased multiple within-burst firing). At rest and in cardiac sinus rhythm, an increased firing probability is seen in both CHF and OSAS patients, whereas increased multiple within-burst firing is found in OSAS but not in CHF. In response to transient sympathoexcitatory stimuli (such as pre-mature heart beats), both patient groups show marked shifts towards multiple within-burst firing. Thus, both mechanisms for augmenting discharge frequency are operating in these two pathological conditions, but the firing characteristics at rest differ significantly. During recording sessions in sympathoexcited patients, we have encountered vasoconstrictor fibres that are active almost exclusively during periods of transient sympathoexcitation, while being virtually silent at rest. This suggests that recruitment of previously inactive vasoconstrictor fibres, the second main alternative for increasing vasoconstrictor output, contributes to transient sympathoexcitatory responses in these patients. Although it seems reasonable to assume that recruitment may also contribute to the resting level of MSNA in CHF and OSAS, this issue is difficult to resolve in microneurographic studies.

Conclusion: In conclusion, pathological sympathoexcitation appears to depend on both recruitment and increased firing frequency. A shift towards multiple within-burst firing, at rest or in response to transient stimuli, may constitute a risk factor per se as it entails neural volleys with high instantaneous firing frequencies and consequently higher release of neurotransmitters.