Cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension at rest and during orthostatic stress: role of the peripheral chemoreflex

Abstract

The baroreflex integrity in early-stage pulmonary arterial hypertension (PAH) remains uninvestigated. A potential baroreflex impairment could be functionally relevant and possibly mediated by enhanced peripheral chemoreflex activity. Thus, we investigated 1) the cardiac baroreflex in non-hypoxemic PAH; 2) the association between baroreflex indexes and peak aerobic capacity (i.e., V̇O2peak); and 3) the peripheral chemoreflex contribution to the cardiac baroreflex. Nineteen patients and 13 age- and sex-matched healthy adults (HA) randomly inhaled either 100% O2 (peripheral chemoreceptors inhibition) or 21% O2 (control session), while at rest and during a repeated sit-to-stand maneuver. Beat-by-beat analysis of R-R intervals and systolic blood pressure provided indexes of cardiac baroreflex sensitivity (cBRS) and effectiveness (cBEI). The PAH group had lower cBEIALL at rest (mean ± SD: PAH = 0.5 ± 0.2 vs HA = 0.7 ± 0.1 a.u., P = 0.02) and lower cBRSALL (PAH = 6.8 ± 7.0 vs HA = 9.7 ± 5.0 ms mmHg-1, P < 0.01) and cBEIALL (PAH = 0.4 ± 0.2 vs HA= 0.6 ± 0.1 a.u., P < 0.01) during the sit-to-stand maneuver versus the HA group. The cBEI during the sit-to-stand maneuver was independently correlated to V̇O2peak (partial r = 0.45, P < 0.01). Hyperoxia increased cBRS and cBEI similarly in both groups at rest and during the sit-to-stand maneuver. Therefore, cardiac baroreflex dysfunction was observed under spontaneous and, most notably, provoked blood pressure fluctuations in non-hypoxemic PAH, was not influenced by the peripheral chemoreflex, and was associated with lower V̇O2peak suggesting it could be functionally relevant.

Enhanced Respiratory Frequency Response to Lower Limb Mechanoreceptors Activation in Patients with Chronic Obstructive Pulmonary Disease

“…Moreover, peripheral chemoreceptors will be stimulated if the patient presents with exercise-induced hypoxemia. In this sense, our group and others have shown synergistic interactions between mechanisms involved in the neural control of ventilation during exercise in healthy humans (24,48), which seem to be potentiated by the presence of cardiorespiratory diseases (33,49,50). Therefore, during active exercise, when the mechanoreflex is activated to a greater extent and plausibly interacts with other neural mechanisms, the mechanoreflex drive to breathe could be of greater magnitude, thereby potentially contributing to the origin of exertional dyspnea and, ultimately, exercise intolerance in patients with COPD.…”

The Systolic Pulmonary Arterial Pressure Liaises Impaired Cardiac Autonomic Control to Pro-inflammatory Status in Systemic Sclerosis Patients

“…Moreover, an impaired baroreflex (16) and chemoreflex (25) sensitivities are associated with disease severity in PAH. Otherwise, it was suggested that the peripheral chemoreflex was not a direct mediator of cardiac baroreflex dysfunction in PAH (26). Thus, the sympathetic overactivity in LHD and PAH could be explained, in part, because of a compensatory response from an augmented neurohumoral activation to compensate harmed cardiac output mechanics (27).…”

Effects of Acute Hypoxia on Heart Rate Variability in Patients with Pulmonary Vascular Disease

“…Autonomic cardiovascular function has been studied in patients with PAH and impaired baroreflex function and increased sympathetic activity has been described [9][10][11][12]. However, the role of autonomic cardiovascular disturbance in progression of PAH or right ventricular dysfunction is not fully understood.…”