Chronic sympathetic attenuation and energy metabolism in autonomic failure

Abstract

The sympathetic nervous system regulates thermogenesis and energy homeostasis in humans. When activated it increases energy expenditure, particularly resting energy expenditure. Most human studies used acute infusion of β-blockers as a model to eliminate sympathetic stimulation and to examine the contribution of the sympathetic nervous system to energy metabolism and balance. Clinically, however, it is also important to assess the effect of chronic sympathetic attenuation on energy metabolism. In this context, we hypothesized that resting energy expenditure is decreased in patients with autonomic failure who, by definition, have low sympathetic tone. We measured 24-hour energy expenditure using whole-room indirect calorimeter in 10 adults with chronic autonomic failure (6 women; age, 64.9±9.1 years; body mass index, 25.2±4.4 kg/m(2)) and 15 sedentary healthy controls of similar age and body composition (8 women; age, 63.1±4.0 years; body mass index, 24.4±3.9 kg/m(2)). In 4 patients, we eliminated residual sympathetic activity with the ganglionic blocker trimethaphan. We found that, after adjusting for body composition, resting energy expenditure did not differ between patients with autonomic failure and healthy controls. However, resting energy expenditure significantly decreased when residual sympathetic activity was eliminated. Our findings suggest that sympathetic tonic support of resting energy expenditure is preserved, at least in part, in pathophysiological models of chronic sympathetic attenuation.

Trial registration: ClinicalTrials.gov NCT00179023.

Figures

Figure 1

Total energy expenditure (EE) and physical activity (PA) in autonomic failure and healthy controls during the 24 hour stay in the whole-room indirect calorimeter. Total energy expenditure was significantly lower in patients with autonomic failure (AF) compared with controls (Panel A). Furthermore, patients with autonomic failure patients have decreased physical activity compared with controls (Panel B).

Figure 2

Resting energy expenditure (REE) measured using whole room indirect calorimeter was similar between patients with autonomic failure compared with controls, P=0.42.

Figure 3

Simple linear regression between resting energy expenditure (REE) and fat free mass (FFM) in patients with autonomic failure (AF), REE= 459.8+21(95% CI 11 to 32)*FFM (Panel A) and healthy controls, REE=426.2+21(95% CI 15 to 30)*FFM (Panel B). Differences in FFM explained 76% of REE variability

Figure 4

Panel A. showed the decrease in resting energy expenditure (REE) during ganglionic blockade in 4 patients with severe autonomic failure. The average decrease in REE was 118 Kcal/day (8%). Panel B. showed the decrease in supine plasma norepinephrine during ganglionic blockade indicating elimination of residual sympathetic tone.

Figure 5

Graphic showed cumulative percentage of BMI in 129 patients with severe autonomic failure referred to the Autonomic Dysfunction Center at Vanderbilt University. Ninety percent of the patients had a BMI less than 30 kg/m2.