Cardiovascular autonomic responses in pre- and post-ganglionic models of chronic autonomic failure

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.