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Original Articles

Muscarinic Receptor Upregulation in Patients With Myocardial Infarction

A New Paradigm

Alejandro N. Mazzadi, PhD; Julien Pineau, MD; Nicolas Costes, PhD; Didier Le Bars, PhD; Franck Bonnefoi, RA; Pierre Croisille, MD, PhD; Raphaël Porcher, PhD and Philippe Chevalier, MD, PhD

From the CERMEP–Imagerie du Vivant (A.N.M., N.C., D.L.B., F.B.), Lyon, France; Hospices Civils de Lyon (J.P., P. Croisille, P. Chevalier), Lyon, France; Université Claude Bernard Lyon 1 (J.P., D.L.B., P. Croisille, P. Chevalier), Lyon, France; and Département de Biostatistique et Informatique Médicale (R.P.), Hôpital Saint Louis, Paris, France.

Correspondence to Philippe Chevalier, MD, PhD, Service de Rythmologie, Hôpital Louis Pradel, BP Lyon Montchat, 69677 BRON Cedex-France. E-mail philippe.chevalier{at}chu-lyon.fr

Received September 17, 2008; accepted June 17, 2009.

Background— Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown.

Methods and Results— Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [¹¹C]methylquinuclidinyl benzilate ([¹¹C]MQNB) in 11 patients 43±20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [¹¹C]MQNB time-activity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy or <70% diameter reduction arteries and without MRI signs of damage; potentially damaged, supplied by infarct-related or >70% diameter reduction arteries and without signs of damage; and damaged, with damage. The muscarinic receptor density in remote (67±30 pmol/mL tissue; n=86) and potentially damaged (71±30 pmol/mL tissue; n=42) regions of patients was higher than in normal regions of volunteers (32±17 pmol/mL tissue; n=156; P<0.001). The muscarinic receptor density in damaged regions (42±21 pmol/mL tissue; n=58) was reduced compared with remote and potentially damaged regions (P<0.001) but was not significantly different from normal regions in volunteers (P=0.093).

Conclusions— Vagal control in patients with chronic myocardial infarction involves muscarinic receptor upregulation in remote nondamaged left ventricular regions. Our results suggest that the receptor density remains within normal values in myocardial regions containing damaged tissue.

Key Words: myocardial infarction • receptors • tomography • MRI

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