Ventilatory and cardiovascular responses to hypercapnia and hypoxia in multiple-system atrophy

Abstract

Background: Loss of medullary sympathoexcitatory neurons may contribute to baroreflex failure, leading to orthostatic hypotension in multiple-system atrophy (MSA). The cardiovascular responses to chemoreflex activation in MSA have not been explored to date.

Objectives: To determine whether ventilatory and cardiovascular responses to hypercapnia and hypoxia during wakefulness are systematically impaired in MSA.

Design: Case-control study.

Setting: Mayo Clinic, Rochester, Minnesota.

Patients: Sixteen patients with probable MSA (cases) and 14 age-matched control subjects (controls).

Main outcome measures: Minute ventilation, blood pressure, and heart rate responses to hypercapnia and hypoxia during wakefulness. Hypercapnia was induced by a rebreathing technique and was limited to a maximal expiratory partial pressure of carbon dioxide of 65 mm Hg. Hypoxia was induced by a stepwise increase in inspiratory partial pressure of nitrogen and was limited to a minimal arterial oxygen saturation of 80%. Ventilatory responses were assessed as slopes of the regression line relating minute ventilation to changes in arterial oxygen saturation and partial pressure of carbon dioxide.

Results: In cases, ventilatory responses to hypercapnia and hypoxia were preserved, despite the presence of severe autonomic failure, while cardiovascular responses to these stimuli were impaired. Among cases, hypercapnia elicited a less robust increase in arterial pressure than among controls, and hypoxia elicited a depressor response rather than the normal pressor responses (P < .001 for both).

Conclusions: Ventilatory responses to hypercapnia and hypoxia during wakefulness may be preserved in patients with MSA, despite the presence of autonomic failure and impaired cardiovascular responses to these stimuli. A critical number of chemosensitive medullary neurons may need to be lost before development of impaired automatic ventilation during wakefulness in MSA, whereas earlier loss of medullary sympathoexcitatory neurons may contribute to the impaired cardiovascular responses in these patients.

Conflict of interest statement

Disclosure: The authors report no conflicts of interest.

Figures

Figure 1

Individual data and average values (mean ± SEM) of ventilatory responses to A - isocapnic hypoxia (H-VR) and B – hypercapnia (HC-VR). Hypoxia induced a significant increase in VE in all subjects without a significant difference between MSA patients and controls. HVR is expressed as the slope of the regression line of VE vs. SaO2. Ventilatory response to hypercapnia, expressed as the slope of the regression line relating VE to PetCO2, was significantly increased in MSA when compared to controls.

Figure 2

Time course of SBP during hyperoxic hypercapnia (left panel) and isocapnic hypoxia (right panel) in MSA patients and control subjects (mean ± SEM). The pressor effect of hypercapnia is blunted in MSA patients when compared to control subjects. During hypoxia, the mild pressor effect observed in controls is reversed in MSA patients, where hypoxia induced a depressor response.