title: Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy.
abstract: Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.
authors.affiliation: Service de Cardiologie et de Chirurgie Cardio-vasculaire, Centre Hospitalo-Universitaire Henri Mondor, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Merlet
authors.forename: J L
authors.initials: JL
authors.lastname: Dubois-Randé
authors.forename: S
authors.initials: S
authors.lastname: Adnot
authors.forename: M H
authors.initials: MH
authors.lastname: Bourguignon
authors.forename: C
authors.initials: C
authors.lastname: Benvenuti
authors.forename: D
authors.initials: D
authors.lastname: Loisance
authors.forename: H
authors.initials: H
authors.lastname: Valette
authors.forename: A
authors.initials: A
authors.lastname: Castaigne
authors.forename: A
authors.initials: A
authors.lastname: Syrota
mesh_terms: D019797:3-Iodobenzylguanidine; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D007462:Iodobenzenes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011877:Radionuclide Imaging; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D007462:Iodobenzenes; D011943:Receptors, Adrenergic, beta; D019797:3-Iodobenzylguanidine; D004280:Dobutamine; D009638:Norepinephrine