Circulation, Vol 79, 344-349, Copyright © 1989 by American Heart Association
EM Gilbert, CC Eiswirth, PC Mealey, P Larrabee, CM Herrick and MR Bristow
An increase in cardiac beta-adrenergic sensitivity or beta-receptor density
or both has been described in several animal species after denervating the
heart. The transplanted human heart is also denervated and, therefore, may
exhibit supersensitivity to beta-adrenergic agonists and an increase in
beta-adrenergic receptor density. In 16 patients examined 1-3 months after
orthotopic cardiac transplantation, beta-adrenergic receptor density
measured by [125I]iodocyanopindolol binding in endomyocardial biopsy
specimens was not significantly different in transplant recipients compared
with normal controls (transplant = 1,429 +/- 199, control = 1,728 +/- 263
fmol/g wet wt; p = NS). However, when normalized to Lowry protein, the
[125I]iodocyanopindolol in beta-adrenergic receptor density in biopsy
tissue from transplant recipients was significantly lower than in tissue
from controls (transplant = 58.1 +/- 6.2, control = 93.5 +/- 13.4 fmol/g
Lowry protein; p = 0.011). Atrial sinus node activity of the denervated
donor heart and the innervated atrial cuff of the native recipient heart
could be detected on the surface electrocardiogram in six patients. In
these six patients, the heart rate response to graded infusions of
epinephrine (taken up by the adrenergic nerve terminals) and isoproterenol
(not taken up by the adrenergic nerve terminals) was measured. The
epinephrine dose-response curve in transplanted donor atria was
significantly to the left of the native recipient atrial dose- response
curve (p less than 0.0001). The isoproterenol dose-response curves for
native and transplanted atria were not different. We conclude that
myocardial beta-adrenergic receptors are not increased in human orthotopic
cardiac allografts and that there is no evidence for beta-receptor-mediated
supersensitivity of postsynaptic origin.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin
Utah Cardiac Transplant Program, Salt Lake City.
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