A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials

Abstract

Augmented peripheral chemoreceptor sensitivity (PChS) is a common feature of many sympathetically mediated diseases, among others, and it is an important mechanism of the pathophysiology of heart failure (HF). It is related not only to the greater severity of symptoms, especially to dyspnea and lower exercise tolerance but also to a greater prevalence of complications and poor prognosis. The causes, mechanisms, and impact of the enhanced activity of peripheral chemoreceptors (PChR) in the HF population are subject to intense research. Several methodologies have been established and utilized to assess the PChR function. Each of them presents certain advantages and limitations. Furthermore, numerous factors could influence and modulate the response from PChR in studied subjects. Nevertheless, even with the impressive number of studies conducted in this field, there are still some gaps in knowledge that require further research. We performed a review of all clinical trials in HF human patients, in which the function of PChR was evaluated. This review provides an extensive synthesis of studies evaluating PChR function in the HF human population, including methods used, factors potentially influencing the results, and predictors of increased PChS.

Keywords: cardiology; heart failure; pathophysiology; peripheral chemoreceptors.

Figure 1

(a) Illustration of the triggers and organic effects of carotid body activation; and (b) Possible causes of carotid body overactivity and its organic complications. Ang II—angiotensin II; CB—carotid body; GFR—glomerular filtration rate; Na⁺—natrium ion; NOS—nitric oxide synthase; PaCO₂—partial pressure of carbon dioxide; PaO₂—partial pressure of oxygen; pH—potential of hydrogen.

Figure 2

(a) Illustration of the transient hypoxia method; (b) Illustration of the isocapnic progressive hypoxic method (rebreathing technique); and (c) Example of the measurement of peripheral chemosensitivity. For each nadir of saturation minute ventilation, heart rate and systolic blood pressure values are plotted. BP—blood pressure; CO₂—carbon dioxide; ECG—electrocardiography; and N₂—nitrogen.