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Circulation, Vol 90, 172-178, Copyright © 1994 by American Heart Association

ARTICLES

In vivo quantification of myocardial muscarinic receptors in heart transplant patients

D Le Guludec, J Delforge, A Syrota, M Desruennes, H Valette, I Gandjbakhch and P Merlet
Service de Medecine Nucleaire, Hopital Bichat, Paris, France.

BACKGROUND: Decreased myocardial adenylate cyclase activity in response to guanine nucleotide stimulation has been recently demonstrated in denervated myocardium of transplant patients, suggesting that changes in left ventricular muscarinic receptors may occur. METHODS AND RESULTS: The concentration and affinity constants of myocardial muscarinic receptors were determined by positron emission tomography with 11C-labeled methylquinuclidinyl benzilate (MQNB), a specific hydrophilic antagonist, in six transplant patients 4.7 +/- 2.3 months after surgery and in six normal subjects. Patients had no sign of cardiac rejection at endomyocardial biopsy. After intravenous injections of MQNB, time-activity curves were obtained over different regions of interest and were fitted to a nonlinear mathematical model. No difference in the concentration of muscarinic receptors was found in transplant patients compared with control subjects: 24 +/- 4 versus 26 +/- 7 pmol/mL tissue, respectively (P = NS). The association rate constant k+1, the dissociation rate constant k-1, and thus the equilibrium-dissociation constant Kd were the same in transplant patients compared with control subjects. CONCLUSIONS: Despite known decreased GTP-stimulated adenylate cyclase activity in transplant patients, the density and affinity constants of myocardial muscarinic receptors are not altered. This suggests abnormalities of the signal- transduction function, such as a change in the guanine nucleotide binding proteins.

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