Schäfers M A, Wichter T, Schäfers K P, Rahman S, Rhodes C G, Lammertsma A A, Lerch H, Knickmeier M, Hermansen F, Schober O, Camici P G, Breithardt G
Department of Nuclear Medicine, Münster University, Germany.
Basic Res Cardiol. 2001 Feb;96(1):91-7. doi: 10.1007/s003950170082.
In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung.
Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET.
Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue).
The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT.
在近期使用正电子发射断层扫描（PET）的体内研究中，我们小组证明，致心律失常性右室心肌病（ARVC）和特发性右室流出道心动过速（RVO-VT）患者的心肌β肾上腺素能受体（βAR）密度降低，且突触前儿茶酚胺清除增加。据推测，心肌βAR密度降低是由于突触前功能障碍导致心肌局部儿茶酚胺增加所致，因为在这些情况下循环血浆儿茶酚胺被证明没有变化。为了进一步证实心脏存在器官局限性肾上腺素能神经功能障碍这一假说，本研究旨在调查另一个胸部器官——肺的βAR密度。
使用非选择性β受体阻滞剂[11C]-CGP 12177和PET，测量7例ARVC患者、8例RVO-VT患者和一组健康对照者（n = 13）的肺和心肌βAR密度。
对照组（12.4±1.7 pmol/g组织）、ARVC患者（11.6±1.7 pmol/g组织，p = 无显著差异）和RVO-VT患者（12.8±2.0 pmol/g组织，p = 无显著差异）的肺βAR密度相似，而与对照组（8.8±1.5 pmol/g组织）相比，ARVC患者（6.3±1.1 pmol/g组织，p = 0.006）和RVO-VT患者（6.8±1.2 pmol/g组织，p = 0.02）的心肌βAR密度显著降低。
在同一患者中，先前描述的心肌βAR密度显著降低的情况下，肺βAR密度未发生变化，这主要支持了我们的病理生理假说，即ARVC和RVO-VT患者的心肌βAR密度可能因心脏器官局限性突触前肾上腺素能功能障碍导致局部突触儿茶酚胺水平升高而降低。由于在本研究中仅测量了肺βAR密度，未来需要进行排除肺βAR脱敏的功能研究，以最终证实ARVC和RVO-VT患者的肺交感神经支配未发生变化。
