Published Online
on July 7, 2009

A more recent version of this article appeared on September 1, 2009

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Original Article

Muscarinic Receptor Upregulation in Patients with Myocardial Infarction: A New Paradigm

Alejandro N. Mazzadi¹; Julien Pineau²; Nicolas Costes¹; Didier Le Bars³; Franck Bonnefoi¹; Pierre Croisille²; Raphaël Porcher⁴ and Philippe Chevalier^2,5

¹ CERMEP—Imagerie du Vivant, Lyon, France;
² Hospices Civils de Lyon (HCL) & Université Claude Bernard Lyon, Lyon, France;
³ CERMEP—Imagerie du Vivant & Université Claude Bernard Lyon, Lyon, France;
⁴ Hôpital Saint Louis, Paris, France

⁵ E-mail: philippe.chevalier{at}chu-lyon.fr

Background—Despite the major role attributed to myocardial vagal activity in left ventricle (LV) arrhythmogenesis in chronic myocardial infarction (MI), the impact of infarction on LV muscarinic receptor density (Bmax) remains unknown.

Methods and Results—The LV Bmax was measured in vivo by positron emission tomography (PET) using the specific antagonist [¹¹C]methylquinuclidinyl benzilate ([¹¹C]MQNB) in 11 patients 43±20 days after MI and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced magnetic resonance imaging (MRI). Three short-axis slices from each subject were analyzed in matched PET and MRI images. A two-injection PET-protocol was used; [¹¹C]MQNB time-activity curves were obtained in six regions per slice and fitted to a three 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; damaged: with damage. The Bmax 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 Bmax in damaged regions (42±21 pmol/ml.tissue; n=58) was reduced compared to 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 MI involves muscarinic receptor upregulation in remote, non-damaged LV regions. Our results suggest that the receptor density remains within normal values in myocardial regions containing damaged tissue.

Key Words: acetylcholine • arrhythmia • infarction • magnetic resonance imaging • myocardial infarction • nervous system, autonomic • receptors • tomography

Related Article

Imaging Left Ventricular Muscarinic Receptor Heterogeneity: A Tool to Evaluate Individuals at Risk for Sudden Death?

James H. Caldwell and Jeanne M. Link
Circ Cardiovasc Imaging 2009 2: 353-355. [Extract] [Full Text] [PDF]

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				J. H. Caldwell and J. M. Link Imaging Left Ventricular Muscarinic Receptor Heterogeneity: A Tool to Evaluate Individuals at Risk for Sudden Death? Circ Cardiovasc Imaging, September 1, 2009; 2(5): 353 - 355. [Full Text] [PDF]