Neuroendocrine and behavioural responses to CO2 inhalation in central versus peripheral autonomic failure.
Multiple system atrophy (MSA) and pure autonomic failure (PAF) represent distinct pathological models of autonomic failure in humans. We have investigated the neuroendocrine, behavioural and autonomic cardiovascular responses to the 35% CO2 challenge. Nine patients with MSA, nine with PAF and five control subjects received a single breath of 35% CO2. Peripheral autonomic failure (i.e., PAF) was associated with significantly lower resting noradrenaline levels. All groups demonstrated a significant pressor response to CO2. In controls, the mean pressor response was +60.2 mm Hg, which was significantly smaller in both the PAF (+26.8 mm Hg, P < 0.01) and MSA (+18.3 mm Hg, P < 0.001) patients. In addition, the onset of the response was significantly delayed in both MSA (140.2 s) and PAF (154.2 s) patients compared with controls (32.4 s, P = 0.04 and P = 0.03, respectively). Noradrenaline levels increased only in controls. Central autonomic impairment (i.e., MSA) was associated with lower cortisol release (+8.8% in MSA compared with +35.2% in control and +23.7% in PAF) and fewer somatic symptoms of emotional arousal. Both MSA and PAF exhibit marked sympathetic autonomic impairment, however, residual (albeit differing) sympathetic pathways can still maintain a partial cardiovascular response. A central autonomic lesion, however, also appears to be associated with blunting of both cortisol and emotional responses to this stress paradigm.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. joey.kaye@health.wa.gov.au
Joey M
JM
Kaye
Tim M
TM
Young
Christopher J
CJ
Mathias
Laura
L
Watson
Stafford L
SL
Lightman
D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000503:physiopathology*; D001519:Behavior / Q000187:drug effects*; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000494:pharmacology*; D016022:Case-Control Studies; D004644:Emotions; D005260:Female; D006801:Humans; D001239:Inhalation; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000502:physiology*
D002245:Carbon Dioxide