Contribution of peripheral and central chemoreceptors to sympatho-excitation in heart failure

Abstract

Chronic heart failure (CHF) is a major public health problem. Tonic hyper-activation of sympathetic neural outflow is commonly observed in patients with CHF. Importantly, sympatho-excitation in CHF exacerbates its progression and is strongly related to poor prognosis and high mortality risk. Increases in both peripheral and central chemoreflex drive are considered markers of the severity of CHF. The principal peripheral chemoreceptors are the carotid bodies (CBs) and alteration in their function has been described in CHF. Mainly, during CHF the CB chemosensitivity is enhanced leading to increases in ventilation and sympathetic outflow. In addition to peripheral control of breathing, central chemoreceptors (CCs) are considered a dominant mechanism in ventilatory regulation. Potentiation of the ventilatory and sympathetic drive in response to CC activation has been shown in patients with CHF as well as in animal models. Therefore, improving understanding of the contribution of the peripheral and central chemoreflexes to augmented sympathetic discharge in CHF could help in developing new therapeutic approaches intended to attenuate the progression of CHF. Accordingly, the main focus of this review is to discuss recent evidence that peripheral and central chemoreflex function are altered in CHF and that they contribute to autonomic imbalance and progression of CHF.

Figure 1. Schematic diagram showing the contribution of peripheral and central chemoreceptors in development of sympathoexcitation and breathing disorders

Carotid body and RTN neurons respond to changes in different signals from the bloodstream and cerebrospinal fluid, respectively. Upon activation, the chemoreflex drive increases and induces a reflex cardiorespiratory response. Integration of the chemosensory inputs takes place in brainstem areas including the NTS, RVLM and central pattern generator, which finally leads to an increase in sympathetic discharges and activation of phrenic motoneurones. In the pathophysiology of CHF, the enhanced activity from peripheral and central chemoreceptors induces an increase in the central symapatho‐respiratory outflow triggering cardiac arrhythmias and breathing disorders. CB, carotid body; CPG, central pattern generator; NTS, nucleus tractus solitarii; RTN, retrotrapezoid nucleus; RVLM, rostral ventrolateral medulla.