Patients with autonomic failure are characterized by disabling orthostatic hypotension (low
blood pressure on standing), and at least half of them also have high blood pressure while
lying down (supine hypertension). Exposure to heat, such as in hot environments, often
worsens their orthostatic hypotension. The causes of this are not fully understood. The
purpose of this study is to evaluate whether applying local heat over the abdomen of
patients with autonomic failure and supine hypertension would decrease their high blood
pressure while lying down. This will help us better understand the mechanisms underlying
this phenomenon, and may be of use in the treatment of supine hypertension.
Primary autonomic failure is a neurodegenerative condition characterized by severe
impairment of the autonomic nervous system. The clinical hallmark of autonomic failure is
disabling orthostatic hypotension, but at least half of patients are also hypertensive while
lying down. This supine hypertension can be severe and associated with end-organ damage and
worsening of orthostatic hypotension due to increased pressure natriuresis. It also
complicates the management of these patients by limiting the use of daytime pressor agents
for the treatment of orthostatic hypotension.
It is well known that heat exposure (e.g. hot weather or a hot bath or shower) produces an
acute and temporary worsening of orthostatic hypotension in autonomic failure patients.
However, the mechanisms underlying this phenomenon are completely unexplored. Factors that
may predispose autonomic failure patients to the acute lowering blood pressure effects of
heat stress include 1) impaired heat dissipation due to inability to sweat, 2) preserved
heat-mediated skin vasodilation, and 3) blunted sympathetic hemodynamic responses to
maintain blood pressure. In this study, we test the hypothesis that moderate levels of local
(abdominal) passive heat stress will lower blood pressure in autonomic failure patients with
To test this hypothesis, we propose this pilot study with the following specific aims:
1. To evaluate the acute blood pressure effects of local passive heat stress in autonomic
failure patients with supine hypertension, we will compare changes in BP between
controlled local heat stress (~44ºC) using a commercial heating pad that covers the
abdomen and part of the torso, and a control (non-heating) study day using the same
heating pad but turned off.
2. To evaluate the mechanisms underlying BP changes during local heat stress, we will
compare changes in hemodynamic parameters (cardiac output, stroke volume and peripheral
vascular resistance), segmental fluid shifts (measured by segmental bioimpedance), skin
blood flow and skin temperature between the heat and non-heating study days.
- Male and female patients, between 18-80 yrs., with primary autonomic failure
(Parkinson Disease, Multiple System Atrophy, and Pure Autonomic Failure) and supine
hypertension. Supine hypertension will be defined as SBP≥150 mmHg.
- Patients able and willing to provide informed consent.
- Significant cardiac, renal or hepatic illness, or with contraindications to
administration of pressor agents or with other factors, which in the investigator's
opinion would prevent the subject from completing the protocol including clinically
significant abnormalities in clinical, mental or laboratory testing.