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(Circulation. 2001;104:2911.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Myocardial Muscarinic Receptor Upregulation and Normal Response to Isoproterenol in Denervated Hearts by Familial Amyloid Polyneuropathy

Nicolas Delahaye, MD; Dominique Le Guludec, MD, PhD; Sylvie Dinanian, MD; Jacques Delforge, PhD; Michel S. Slama, MD; Laure Sarda, MD; Frédéric Dollé, PhD; Hichem Mzabi, MD; Didier Samuel, MD; David Adams, MD; André Syrota, MD, PhD; Pascal Merlet, MD, PhD

From Service de Médecine Nucléaire, Hôpital Bichat, AP-HP, Paris, France (N.D., D.L.G.); Service de Cardiologie, Hôpital A. Béclère, AP-HP, Paris, France (S.D., M.S.S.); Service Hospitalier Frédéric Joliot, DRM, DSV-CEA, Orsay, France (J.D., L.S., F.D., A.S., P.M.); Service de Chirurgie Hépatique, Hôpital P. Brousse, AP-HP, Paris, France (H.M., D.S.); and Service de Neurologie, Hôpital Bicètre, AP-HP, Paris, France (D.A.).

Correspondence to Nicolas Delahaye, MD, Service de Médecine Nucléaire-Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France. E-mail nicolas.delahaye{at}laposte.net

Background— Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated.

Methods and Results— Twenty-one patients were studied (age, 39±11 years; normal coronary arteries; left ventricular ejection fraction 68±9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with ¹¹C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac ß-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'_max, 35.5±8.9 versus 26.1±6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (HR after atropine, 11±21% versus 62±17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects.

Conclusions— Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac ß-receptor responsiveness to catecholamines.

Key Words: nervous system, autonomic • amyloid • receptors