Stevens M J, Raffel D M, Allman K C, Dayanikli F, Ficaro E, Sandford T, Wieland D M, Pfeifer M A, Schwaiger M
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0678, USA.
Circulation. 1998 Sep 8;98(10):961-8. doi: 10.1161/01.cir.98.10.961.
Regional cardiac sympathetic hyperactivity predisposes to malignant arrhythmias in nondiabetic cardiac disease. Conversely, however, cardiac sympathetic denervation predicts increased morbidity and mortality in severe diabetic autonomic neuropathy (DAN). To unite these divergent observations, we propose that in diabetes regional cardiac denervation may elsewhere induce regional sympathetic hyperactivity, which may in turn act as a focus for chemical and electrical instability. Therefore, the aim of this study was to explore regional changes in sympathetic neuronal density and tone in diabetic patients with and without DAN.
PET using the sympathetic neurotransmitter analogue 11C-labeled hydroxyephedrine ([11C]-HED) was used to characterize left ventricular sympathetic innervation in diabetic patients by assessing regional disturbances in myocardial tracer retention and washout. The subject groups comprised 10 diabetic subjects without DAN, 10 diabetic subjects with mild DAN, 9 diabetic subjects with severe DAN, and 10 healthy subjects. Abnormalities of cardiac [11C]-HED retention were detected in 40% of DAN-free diabetic subjects. In subjects with mild neuropathy, tracer defects were observed only in the distal inferior wall of the left ventricle, whereas with more severe neuropathy, defects extended to involve the distal and proximal anterolateral and inferior walls. Absolute [11C]-HED retention was found to be increased by 33% (P<0.01) in the proximal segments of the severe DAN subjects compared with the same regions in the DAN-free subjects (30%; P<0.01 greater than the proximal segments of the mild DAN subjects). Despite the increased tracer retention, no appreciable washout of tracer was observed in the proximal segments, consistent with normal regional tone but increased sympathetic innervation. Distally, [11C]-HED retention was decreased in severe DAN by 33% (P<0.01) compared with the DAN-free diabetic subjects (21%; P<0.05 lower than the distal segments of the mild DAN subjects).
Diabetes may result in left ventricular sympathetic dysinnervation with proximal hyperinnervation complicating distal denervation. This combination could result in potentially life-threatening myocardial electrical instability and explain the enhanced cardioprotection from beta-blockade in these subjects.
在非糖尿病性心脏疾病中，局部心脏交感神经功能亢进易引发恶性心律失常。然而，相反的是，心脏交感神经去神经支配预示着严重糖尿病自主神经病变（DAN）患者的发病率和死亡率增加。为了统一这些不同的观察结果，我们提出，在糖尿病患者中，局部心脏去神经支配可能在其他部位诱发局部交感神经功能亢进，进而可能成为化学和电不稳定的焦点。因此，本研究的目的是探讨有无DAN的糖尿病患者交感神经元密度和张力的局部变化。
使用交感神经递质类似物11C标记的羟基麻黄碱（[11C]-HED）进行正电子发射断层扫描（PET），通过评估心肌示踪剂滞留和清除的局部异常情况，来表征糖尿病患者左心室的交感神经支配情况。研究对象包括10名无DAN的糖尿病患者、10名轻度DAN的糖尿病患者、9名重度DAN的糖尿病患者和10名健康受试者。在40%无DAN的糖尿病患者中检测到心脏[11C]-HED滞留异常。在轻度神经病变患者中，仅在左心室远端下壁观察到示踪剂缺损，而在更严重的神经病变患者中，缺损扩展至累及远端和近端前外侧壁及下壁。与无DAN患者的相同区域相比，重度DAN患者近端节段的绝对[11C]-HED滞留增加了33%（P<0.01）（比轻度DAN患者近端节段高30%；P<0.01）。尽管示踪剂滞留增加，但在近端节段未观察到明显的示踪剂清除，这与局部张力正常但交感神经支配增加一致。在远端，与无DAN的糖尿病患者相比，重度DAN患者的[11C]-HED滞留降低了33%（P<0.01）（比轻度DAN患者远端节段低21%；P<0.05）。
糖尿病可能导致左心室交感神经去神经支配异常，近端神经支配增加并伴有远端去神经支配。这种组合可能导致潜在的危及生命的心肌电不稳定，并解释了这些患者从β受体阻滞剂中获得增强的心脏保护作用的原因。
