From the Autonomic Dysfunction Center, Vanderbilt University, Nashville,
Tenn.
Abstract—Pure autonomic failure has
been conceptualized as deficient sympathetic and parasympathetic
innervation. Several recent observations in chronic autonomic failure,
however, cannot be explained simply by loss of autonomic innervation,
at least according to our current understanding. To simulate acute
autonomic failure, we blocked NN-nicotinic receptors with
intravenous trimethaphan (6±0.4 mg/min) in 7 healthy
subjects (4 men, 3 women, aged 32±3 years, 68±4 kg, 171±5 cm).
NN-Nicotinic receptor blockade resulted in near-complete
interruption of sympathetic and parasympathetic efferents as indicated
by a battery of autonomic function tests. With trimethaphan, small
postural changes from the horizontal were associated with significant
blood pressure changes without compensatory changes in heart rate.
Gastrointestinal motility, pupillary function, saliva
production, and tearing were profoundly suppressed with
trimethaphan. Plasma norepinephrine level decreased from
1.1±0.12 nmol/L (180±20 pg/mL) at baseline to 0.23±0.05 nmol/L
(39±8 pg/mL) with trimethaphan (P<.001). There was a
more than 16-fold increase in plasma vasopressin
(P<.01) and no change in plasma renin activity. We
conclude that blockade of NN-cholinergic receptors is
useful to simulate the hemodynamic alterations of acute
autonomic failure in humans. The loss of function with acute
NN-cholinergic blockade is more complete than in most cases
of chronic autonomic failure. This difference may be exploited to
elucidate the contributions of acute denervation and chronic adaptation
to the pathophysiology of autonomic failure. NN-Cholinergic
blockade may also be applied to study human
cardiovascular physiology and pharmacology in the
absence of confounding baroreflexes.
© 1998 American Heart Association, Inc.
Scientific Contributions
NN-Nicotinic Blockade as an Acute Human Model of Autonomic Failure
Key Words: autonomic nervous system • hypotension • trimethaphan • receptors, cholinergic • catecholamines • vasopressin
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