Development of myocardial beta-adrenergic receptor density and adenylate cyclase activity after human heart transplantation

Abstract

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.