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Selegiline improves cardiac sympathetic
terminal function and beta-adrenergic responsiveness in heart failure
Shite J, Dong E, Kawai H, Stevens SY, Liang CS
Cardiology Unit,
Department of Medicine
Department of Neurobiology and Anatomy,
University of Rochester Medical Center,
Rochester, New York 14642.
Am J Physiol Heart Circ Physiol 2000 Sep; 279(3):H1283-H1290
ABSTRACT
Selegiline is a centrally acting sympatholytic
agent with neuroprotective properties. It also has been shown to promote
sympathetic reinnervation after sympathectomy. These actions of selegiline
may be beneficial in heart failure that is characterized by increased
sympathetic nervous activity and functional sympathetic denervation. Twenty-seven rabbits with rapid cardiac pacing (360 beats/min, 8 wk) and
twenty-three rabbits without pacing were randomly assigned to receive
selegiline (1 mg/day, 8 wk) or placebo. Rapid pacing increased plasma
norepinephrine (NE) and decreased left ventricular fractional shortening,
baroreflex sensitivity, cardiac sympathetic nerve terminal profiles, cardiac
NE uptake activity, and myocardial beta-adrenoceptor density. Selegiline
administration to animals with rapid ventricular pacing attenuated the
increase in plasma NE and decreases in fractional shortening, baroreflex
sensitivity, sympathetic nerve profiles, NE uptake activity and beta-adrenoceptor
density. Thus selegiline appears to exert a sympatholytic and cardiac
neuroprotective effect in pacing-induced cardiomyopathy. The effects are
potentially beneficial because selegiline not only improves cardiac function
but also increases baroreflex sensitivity in heart failure.
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