Development of myocardial beta-adrenergic receptor density and adenylate cyclase activity after human heart transplantation.
An increase in basal heart rate caused by a lack of vagal control and chronotropic supersensitivity to epinephrine has been shown in transplanted human hearts. Prejunctional and/or postjunctional origins for this supersensitivity have been suggested, the latter involving changes in the number of myocardial beta-adrenergic receptors or in the receptor adenylate cyclase system. To directly determine the time course of change, serial determinations were performed during the first 3 months after heart transplantation. The beta-adrenergic receptor density measured by iodine 125-labelled iodocyanopindolol binding in 61 endomyocardial biopsy specimens (a mean of 6.1 +/- 0.58 biopsies from each of 10 patients) showed great intraindividual and interindividual variability (56.6 +/- 6.8 fmol/mg protein) with no mean trend toward gradually changing receptor densities. Isoproterenol-stimulated adenylate cyclase activity measured in 33 biopsy specimens (a mean of 5.5 +/- 0.67 biopsy specimens from each of six patients) varied considerably (112.5 +/- 13.8 pmol cyclic adenosine monophosphate/mg protein/min), again with no definite tendency with regard to the development over time. The beta-adrenergic receptor densities showed no statistical correlation with the degree of rejection as assessed by histologic criteria and antimyosin ration. These results suggest that in the first 3 months after heart transplantation beta-adrenergic receptor density and adenylate cyclase responses to 10 mumol/L isoproterenol do not change and that beta-adrenergic receptor density in the transplanted myocardium does not seem to be affected by the degree of rejection.
Cruz Caturla
M
M
Cardiac Catheterization Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Masotti
M
M
Brodde
O E
OE
Hjemdahl
P
P
Velasquez
D
D
Turá
A
A
Crexells
C
C
D000262:Adenylyl Cyclases / Q000378:metabolism*; D001706:Biopsy; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D020120:Iodocyanopindolol; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010869:Pindolol / Q000031:analogs & derivatives; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases