Sympatho–Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation

Abstract

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case–control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.

Effects of oxygen supplementation in autonomic nervous system function during exercise in patients with idiopathic pulmonary fibrosis and exertional desaturation

“…Moreover, a recent study in pulmonary patients awaiting transplantation, reported that patients with more severe lung disease showed an autonomic profile characterized by a prevalent cardiac vagal respiratory modulation and a loss of sympathetic efference compared to less severe lung disease patients. 4 In support, Volterrani et al also reported an increase in vagal activity (as indicated by an increased high-frequency HRV power) in non-hypoxemic or in mildly hypoxemic COPD patients, which was suggested to be associated with reduced FEV 1 and an increased bronchoconstriction. 31 In that study, patients were also less able to respond to sympathetic and parasympathetic stimuli, compared with the healthy subjects, which is in line with our findings in IPF.…”

“…Tobaldini et al reported autonomic dysregulation in patients with end-stage lung disease awaiting transplantation. 4 In patients with chronic obstructive pulmonary disease (COPD), although diurnal variation in heart rate variability (HRV) was normal, impairments in HRV during a stimulus have been reported. 5,6 Long-term oxygen therapy seems to improve the HRV dysfunctions.…”

Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study

“…It was shown that double lung transplant recipients could have compatible responses with complete cardiac denervation (i.e., compared to heart–lung transplanted) [ 6 ]. Besides, after double lung transplant, patients had an abnormal heart rate and blood pressure responses during autonomic tests (e.g., Valsalva manoeuvre and adenosine administration) [ 7 ].…”

“…Indeed, it was widely documented in current literature that breathing is a powerful modulator of heart rate variability (HRV) [ 4 ]. HRV analysis has proven to be a reliable, non-invasive method to investigate the autonomic neural modulation of cardiovascular functions, and a decline of HRV has shown to be related to higher cardiovascular risk and poor prognosis [ 5 , 6 ].…”

Autonomic Nervous System: From Bench to Bedside

“…Similarly, the application of HRV in other settings such as pulmonary diseases revealed interesting novel data. In fact, in comparison to healthy subjects, patients with end-stage lung diseases awaiting lung transplantation showed a predominant sympathetic modulation and lower markers of vagal modulation, but the more severe the disease, the lower the sympathetic control [ 8 ].…”