IN-VIVO QUANTIFICATION OF MYOCARDIAL MUSCARINIC RECEPTORS IN HEART-TRANSPLANT PATIENTS

Background Decreased myocardial adenylate cyclase activity in response to guanine nucleotide stimulation has been recently demonstrated in d enervated myocardium of transplant patients, suggesting that changes i n left ventricular muscarinic receptors may occur. Methods and Results The concentration and affinity constants of myocardial muscarinic rec eptors were determined by positron emission tomography with C-11-label ed methylquinuclidinyl benzilate (MQNB), a specific hydrophilic antago nist, in six transplant patients 4.7+/-2.3 months after surgery and in six normal subjects. Patients had no sign of cardiac rejection at end omyocardial biopsy. After intravenous injections of MQNB, time-activit y curves were obtained over different regions of interest and were fit ted to a nonlinear mathematical model. No difference in the concentrat ion of muscarinic receptors was found in transplant patients compared with control subjects: 24+/-4 versus 26+/-7 pmol/mL tissue, respective ly (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. Concl usions Despite known decreased GTP-stimulated adenylate cyclase activi ty in transplant patients, the density and affinity constants of myoca rdial muscarinic receptors are not altered. This suggests abnormalitie s of the signal-transduction function, such as a change in the guanine nucleotide binding proteins.