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(Hypertension. 2001;37:1357.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Animal Model of Neuropathic Tachycardia Syndrome
Presented in part at the annual meetings of the Society of Neuroscience, Miami, Fla, October 28, 1999, and the American Autonomic Society, Kona, Hawaii, November 1, 1999.
From the Departments of Pharmacology, Medicine, and Neurology, Vanderbilt University, Nashville, Tenn.
Correspondence to David Robertson, MD, Clinical Research Center, AA3228 MCN, Vanderbilt University, Nashville, TN 37232. E-mail david.robertson{at}mcmail.vanderbilt.edu
Abstract—Clinically
relevant autonomic dysfunction can result from either complete or
partial loss of sympathetic outflow to effector organs. Reported animal
models of autonomic neuropathy have aimed to achieve
complete lesions of sympathetic nerves, but incomplete lesions might be
more relevant to certain clinical entities. We hypothesized that loss
of sympathetic innervation would result in a predicted decrease in
arterial pressure and a compensatory increase in heart
rate. Increased heart rate due to loss of sympathetic innervation is
seemingly paradoxical, but it provides a mechanistic explanation for
clinical autonomic syndromes such as neuropathic postural
tachycardia syndrome. Partially dysautonomic animals were
generated by selectively lesioning postganglionic sympathetic neurons
with 150 mg/kg 6-hydroxydopamine hydrobromide in
male Sprague-Dawley rats. Blood pressure and heart rate were monitored
using radiotelemetry. Systolic blood pressure decreased within
hours postlesion (
>20 mm Hg). Within 4 days postlesion, heart
rate rose and remained elevated above control levels. The severity of
the lesion was determined functionally and pharmacologically by
spectral analysis and responsiveness to tyramine. Low-frequency
spectral power of systolic blood pressure was reduced
postlesion and correlated with the diminished tyramine responsiveness
(r=0.9572,
P=0.0053). The
tachycardia was abolished by treatment with the
ß-antagonist propranolol, demonstrating that
it was mediated by catecholamines acting on cardiac
ß-receptors. Partial lesions of the autonomic nervous system have
been hypothesized to underlie many disorders, including neuropathic
postural tachycardia syndrome. This animal model may help
us better understand the pathophysiology of autonomic dysfunction and
lead to development of therapeutic interventions.
Key Words: blood pressure • rats • sympathectomy • tachycardia • heart rate
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