Central role of carotid body chemoreceptors in disordered breathing and cardiorenal dysfunction in chronic heart failure

Abstract

Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. Elimination of CB afferents in experimental models of CHF has been shown to reduce OB, respiratory-sympathetic coupling, and renal SNA, and to improve autonomic balance in the heart. The CB chemoreceptors may play an important role in progression of CHF by contributing to respiratory instability and OB, which in turn further exacerbates tonic and chemoreflex-evoked increases in SNA to the heart and kidney.

Influence of central apneas and chemoreflex activation on pulmonary artery pressure in chronic heart failure

“…Patients with CSR also showed a significant increase in chemosensitivity to either hypoxia or hypercapnia. An increase in chemoreflex sensitivity is not only a main mechanism underlying CSR onset and maintenance [15,16], but also a main determinant in the increase in the adrenergic surge [15,16,36,37], as confirmed by the finding of elevated plasma norepinephrine levels. The finding of a sympathetic predominance on the background of impaired autonomic balance is corroborated by marked reduction in heart rate variability indexes.…”

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

“…; Marcus et al . b , ). In addition, respiratory–sympathetic coupling has been pointed out as a key pathophysiological mechanism in other disease conditions such as hypertension and sleep apnoea.…”

“…; Marcus et al . b ). In addition, during hypoxaemic/hypercapnic stimulation, the CBs also activate the sympathetic nervous system to maintain arterial pressure and to guarantee adequate blood flow to target organs, especially the heart and brain (Schultz & Sun, ).…”

“… b ; Marcus et al . b ). In addition to these promising findings in pre‐clinical models, the therapeutic value of modulating the CB‐mediated chemoreflex drive has also been addressed in human CHF.…”

“…a ; Marcus et al . b ). It is worth noting that the contribution of CB‐mediated peripheral chemoreflex drive to autonomic imbalance and disordered breathing patterns has only been studied in systolic heart failure.…”