Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin.
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)
Gilbert
E M
EM
Utah Cardiac Transplant Program, Salt Lake City.
Eiswirth
C C
CC
Mealey
P C
PC
Larrabee
P
P
Herrick
C M
CM
Bristow
M R
MR
D000328:Adult; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D004837:Epinephrine