Increased Myocardial Muscarinic Receptor Density in Idiopathic Dilated Cardiomyopathy

Abstract

Background Congestive heart failure is associated with decreased stimulated myocardial adenylate cyclase activity, increased G i -binding protein, attenuated parasympathetic tone, and increased modulation of β-adrenergic inotropic left ventricular stimulation by parasympathetic agonists. Despite these abnormalities, changes in the density or affinity of ventricular muscarinic receptors have not been demonstrated in patients. Methods and Results The density and affinity constants of myocardial muscarinic receptors were evaluated noninvasively by means of positron emission tomography with 11 C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, in 20 patients with congestive heart failure due to idiopathic dilated cardiomyopathy (mean left ventricular ejection fraction, 22±9%) and compared with values in 12 normal subjects. The mean receptor concentration was significantly higher in patients than in control subjects ( B′ max , 34.5±8.9 versus 25±7.7 pmol/mL, P <.005), with no changes in affinity constants. The change in heart rate after injection of 0.6 mg of cold MQNB was lower in patients than in control subjects (34±20% versus 55±36%, P <.05), and receptor density correlated negatively with maximal heart rate in the patients ( r =.45, P <.05). Conclusions Congestive heart failure is associated with an upregulation of myocardial muscarinic receptors. This may be an adaptive mechanism to β-agonist stimulation and should increase the number of potential targets for pharmacological intervention.