Bilateral carotid body resection – a challenge for blood oxygen homeostasis

Abstract

The carotid body, located bilaterally at the bifurcation of the common carotid artery, is a sensor that has the principal task of monitoring the partial pressure of oxygen (PO2 ) and carbon dioxide (PCO2 ) within the blood. Reductions in PO2 (that is, hypoxia) or increases in PCO2 (that is, hypercapnia) increase afferent activity in the carotid sinus nerve, are integrated within the brainstem, and the consequent efferent responses lead to hyperventilation and sympathoexcitation in an attempt to restore adequate alveolar ventilation and the preservation of oxygen delivery for vital organs. Whilst there is redundancy in the human body for the sensing and maintenance of blood PCO2 levels (that is, central chemoreceptors), the carotid body is the predominant oxygen sensor responsible for the hypoxic peripheral chemoreceptor reflex. Plasticity within the afferent arm of the carotid body in response to hypoxia can sensitize the peripheral chemoreceptor reflex leading to instability in the control of breathing and chronically elevated sympathetic activity. For example, increased sensitivity of the peripheral chemoreceptor reflex contributes to periodic breathing during sleep at high altitude, the waxing and waning of breathing commonly associated with congestive heart failure, and hyperactivity of the sympathetic nervous system in heart failure, obstructive sleep apnoea and drug-resistant hypertension. Consequently, surgical resection of the carotid bodies has recently been studied as a treatment to reduce sympathetic tone and carotid body chemosensitivity in patients with systolic heart failure (Niewinski et al. 2017). Surgical resection of one or both carotid bodies has been conducted over the past ∼80 years to treat rare carotid body tumours and as an experimental treatment for a number of respiratory diseases including asthma and chronic obstructive pulmonary disease. Owing to ethical and safety considerations, studies typically involve small sample sizes, but have offered a unique opportunity to better understand the role the carotid body plays in cardiorespiratory control (Honda, 1985; Timmers et al. 2003). In general, these studies have demonstrated severe and long-lasting attenuation/abolishment of the hypoxic ventilatory response, chronic attenuation of the sympathetic baroreflex, and only a modest attenuation of the hypercapnic ventilatory response. As might be expected, ∼50% of the ventilatory response to hypoxia remains following unilateral resection compared with bilateral carotid body resection (Honda, 1985; Niewinski et al. 2017). Considering 8 decades of research into carotid body resection, the field has progressed slowly and the clinical benefits associated with the procedure are not impressive. For example, carotid body resection while reducing sympathetic tone only modestly improved exercise tolerance with little additional clinical benefit (Niewinski et al. 2017). In this issue of The Journal of Physiology, Niewinski et al (2021) compared the dynamics of blood oxygen desaturation during mild and moderate hypoxia in a small sample of congestive heart failure patients (n = 4) who had undergone bilateral carotid body resection 5 years prior with age-matched heart failure patients and healthy participants with intact carotid bodies. While the sample size does not afford formal hypothesis testing, the comparison of individual responses across the three groups offers a unique narrative with respect to oxygenation pattern, ventilatory and haemodynamic responses in a group of patients not readily accessible. The hypoxic ventilatory response was larger in congestive heart failure patients compared with healthy controls, and bilateral carotid body resection virtually abolished the hypoxic ventilatory response at 3 months and 5 years post-surgery. Given the experimental design, it would have been interesting to validate an experimental technique frequently utilized in the field to suppress carotid body activity and to estimate the carotid body’s tonic contribution to eupnoea and support of central sympathetic outflow. One approach to this is to conduct repeat trials of breathing 100% O2 and to measure the associated depression in ventilation and/or muscle sympathetic nerve activity (Prasad et al. 2020). Tomy knowledge this approach has never been validated following carotid body resection but in doing so would validate a useful experimental approach for testing future pharmacological strategies for reducing carotid body activity without the need for surgical resection. Alternatively, it may help identify patients whose phenotype might warrant carotid body resection as a therapeutic strategy. The novelty in the work by Niewinski et al (2021) is in the assessment of blood oxygen saturation during exposure to mild (15% O2, ∼2700 m) and moderate hypoxia (12% O2, ∼4500 m). Minimum blood oxygen saturation was generally 10% lower in congestive heart failure patients and the variability of blood oxygen saturation was much greater following bilateral carotid body resection compared with both carotid body intact and healthy controls. While this generally poor ability to maintain stable oxygen saturation may carry added clinical risk, particularly in patients with added cardiovascular comorbidities, the wakefulness drive to breathe appears to constrain any unattended oxygen desaturations. Whether blood oxygen variability is any worse during sleep when the wakefulness drive is lost and co-morbid obstructive sleep apnoea may be exacerbated remains to be determined. Likewise, it would have been interesting to evaluate the effects of carotid body resection on ventilatory drive and blood oxygen dynamics during exercise both in normoxia and hypoxia. Patients with severe congestive heart failure typically desaturate during exercise and it is likely that carotid body resection would worsen this effect. While bilateral carotid body resection in congestive heart failure patients leads to reductions in sympathetic tone, the greater hypoxaemia and high variability in blood oxygen saturation commensurate with a loss of hypoxic ventilatory response