Merlet P, Dubois-Randé J L, Adnot S, Bourguignon M H, Benvenuti C, Loisance D, Valette H, Castaigne A, Syrota A
Service de Cardiologie et de Chirurgie Cardio-vasculaire, Centre Hospitalo-Universitaire Henri Mondor, Créteil, France.
J Cardiovasc Pharmacol. 1992 Jan;19(1):10-6. doi: 10.1097/00005344-199201000-00002.
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.
心肌β-肾上腺素能受体脱敏可能是由于去甲肾上腺素（NE）神经元摄取功能受损以及循环中NE浓度升高所致。在18例与特发性扩张型心肌病相关的充血性心力衰竭患者中，研究了这两种脱敏机制各自的作用。通过[123I]间碘苄胍（MIBG）闪烁显像评估神经元NE摄取系统。β-肾上腺素能受体的脱敏水平通过冠状动脉内注入多巴酚丁胺期间左心室（LV）dP/dt峰值的净增加来评估。在基线时测定动脉NE浓度。为了获得对照值，我们对12名正常受试者进行了MIBG闪烁显像并测定了基线NE浓度。与对照组相比，患者的心脏MIBG摄取显著降低。基于血流动力学指标，这种降低与疾病的严重程度相关。心力衰竭患者对冠状动脉内注入多巴酚丁胺的变力反应与基线NE浓度升高和心脏MIBG摄取减少均相关（r分别为-0.63，p<0.01和r=0.73，p<0.001）。这些发现表明，脱敏过程与神经元NE摄取功能受损和循环中NE浓度升高均相关。此外，还确定了11例中度心力衰竭患者的亚组，他们的心脏MIBG摄取减少但循环NE浓度正常。这表明NE摄取功能受损是特发性心肌病脱敏的早期机制。心脏MIBG显像可能是评估心力衰竭患者严重程度的一种非侵入性手段，也可用于评估治疗对肾上腺素能途径心肌改变的效果。
