Cardiovascular autonomic responses in pre- and post-ganglionic models of chronic autonomic failure
Author(s)
Young, Tim
Type
Thesis
Abstract
Multiple System Atrophy (MSA) and Pure Autonomic Failure (PAF) are contrasting models
of Chronic Autonomic failure. PAF primarily involves the post-ganglionic autonomic nervous
system, whilst in MSA the pre-ganglionic structures are impaired. My central hypothesis is
that this underlying neuropathological difference between MSA and PAF will lead to
differing cardiovascular responses.
I will assess the cardiovascular effects of known pressor and vasomotor stimuli (mental
arithmetic, cold pressor test, isometric exercise, water ingestion, inhaled CO2 and inspiratory
gasp) in MSA and PAF. Neurohormonal aspects will be explored by comparing the
cardiovascular effects of the α2-adrenoceptor agonist clonidine with serum noradrenaline
levels in these groups, as well as comparing supine antidiuretic hormone (ADH) levels after
head up tilt and correlating these with supine blood pressure (BP). As well as contrasting the
cardiovascular responses, I will use the water ingestion studies to examine effects on
orthostatic hypotension, a common complication of both MSA and PAF.
To measure cardiovascular responses during these studies I have used the Portapres II device
to obtain continuous, non-invasive, beat-to-beat measurements of BP and heart rate (HR).
Subsequent Model flow analysis using Beatscope software has then been used to calculate
further cardiovascular indices, including cardiac output (CO), stroke volume (SV) and total
peripheral resistance (TPR). In addition, intermittent BP and HR measurements have been
obtained with an automated sphygmomanometer (Dinamap). Finally, peripheral vasomotor
responses have been recorded by means of the Laser Doppler perfusion meter.
of Chronic Autonomic failure. PAF primarily involves the post-ganglionic autonomic nervous
system, whilst in MSA the pre-ganglionic structures are impaired. My central hypothesis is
that this underlying neuropathological difference between MSA and PAF will lead to
differing cardiovascular responses.
I will assess the cardiovascular effects of known pressor and vasomotor stimuli (mental
arithmetic, cold pressor test, isometric exercise, water ingestion, inhaled CO2 and inspiratory
gasp) in MSA and PAF. Neurohormonal aspects will be explored by comparing the
cardiovascular effects of the α2-adrenoceptor agonist clonidine with serum noradrenaline
levels in these groups, as well as comparing supine antidiuretic hormone (ADH) levels after
head up tilt and correlating these with supine blood pressure (BP). As well as contrasting the
cardiovascular responses, I will use the water ingestion studies to examine effects on
orthostatic hypotension, a common complication of both MSA and PAF.
To measure cardiovascular responses during these studies I have used the Portapres II device
to obtain continuous, non-invasive, beat-to-beat measurements of BP and heart rate (HR).
Subsequent Model flow analysis using Beatscope software has then been used to calculate
further cardiovascular indices, including cardiac output (CO), stroke volume (SV) and total
peripheral resistance (TPR). In addition, intermittent BP and HR measurements have been
obtained with an automated sphygmomanometer (Dinamap). Finally, peripheral vasomotor
responses have been recorded by means of the Laser Doppler perfusion meter.
Date Issued
2008
Date Awarded
2009-11
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Mathias, Christopher
Sponsor
The Sarah Matheson Trust
Creator
Young, Tim
Publisher Department
Neurovascular Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)