Increased myocardial muscarinic receptor density in idiopathic dilated cardiomyopathy: an in vivo PET study.
BACKGROUND
Congestive heart failure is associated with decreased stimulated myocardial adenylate cyclase activity, increased Gi-binding protein, attenuated parasympathetic tone, and increased modulation of beta-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.


RESULTS
The density and affinity constants of myocardial muscarinic receptors were evaluated noninvasively by means of positron emission tomography with 11C-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 beta-agonist stimulation and should increase the number of potential targets for pharmacological intervention.
Le Guludec
D
D
Service de Medecine Nucléaire, Hôpital Bichat, Paris, France.
Cohen-Solal
A
A
Delforge
J
J
Delahaye
N
N
Syrota
A
A
Merlet
P
P
D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012016:Reference Values; D014055:Tomography, Emission-Computed
D011976:Receptors, Muscarinic