Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, UK.
INSIGNEO Institute for in silico Medicine, University of Sheffield, Sheffield, UK.
Diabetologia. 2020 May;63(5):1066-1071. doi: 10.1007/s00125-020-05106-7. Epub 2020 Feb 7.
AIMS/HYPOTHESIS: We examined the effect of a standardised sympathetic stimulus, incremental adrenaline (epinephrine) infusion on cardiac repolarisation in individuals with type 1 diabetes with normal autonomic function, subclinical autonomic neuropathy and established autonomic neuropathy.
Ten individuals with normal autonomic function and baroreceptor sensitivity tests (NAF), seven with subclinical autonomic neuropathy (SAN; normal standard autonomic function tests and abnormal baroreceptor sensitivity tests); and five with established cardiac autonomic neuropathy (CAN; abnormal standard autonomic function and baroreceptor tests) underwent an incremental adrenaline infusion. Saline (0.9% NaCl) was infused for the first hour followed by 0.01 μg kg min and 0.03 μg kg min adrenaline for the second and third hours, respectively, and 0.06 μg kg min for the final 30 min. High resolution ECG monitoring for QT duration, ventricular repolarisation parameters (T wave amplitude, T wave area symmetry ratio) and blood sampling for potassium and catecholamines was performed every 30 min.
Baseline heart rate was 68 (95% CI 60, 76) bpm for the NAF group, 73 (59, 87) bpm for the SAN group and 84 (78, 91) bpm for the CAN group. During adrenaline infusion the heart rate increased differently across the groups (p = 0.01). The maximum increase from baseline (95% CI) in the CAN group was 22 (13, 32) bpm compared with 11 (7, 15) bpm in the NAF and 10 (3, 18) bpm in the SAN groups. Baseline QT was 382 (95% CI 374, 390) ms in the NAF, 378 (363, 393) ms in the SAN and 392 (367, 417) ms in the CAN groups (p = 0.31). QT in all groups lengthened comparably with adrenaline infusion. The longest QT was 444 (422, 463) ms (NAF), 422 (402, 437) ms (SAN) and 470 (402, 519) ms (CAN) (p = 0.09). T wave amplitude and T wave symmetry ratio decreased and the maximum decrease occurred earlier, at lower infused adrenaline concentrations in the CAN group compared with NAF and SAN groups. AUC for the symmetry ratio was different across the groups and was lowest in the CAN group (p = 0.04). Plasma adrenaline rose and potassium fell comparably in all groups.
CONCLUSIONS/INTERPRETATION: Participants with CAN showed abnormal repolarisation in some measures at lower adrenaline concentrations. This may be due to denervation adrenergic hypersensitivity. Such individuals may be at greater risk of cardiac arrhythmias in response to physiological sympathoadrenal challenges such as stress or hypoglycaemia.
目的/假设：我们研究了在具有正常自主神经功能、亚临床自主神经病变和已建立自主神经病变的 1 型糖尿病患者中，标准化交感刺激递增肾上腺素（肾上腺素）输注对心脏复极的影响。
10 名具有正常自主神经功能和压力感受器敏感性测试（NAF）的个体、7 名具有亚临床自主神经病变（SAN；正常标准自主神经功能测试和异常压力感受器敏感性测试）的个体和 5 名具有已建立的心脏自主神经病变（CAN；异常标准自主神经功能和压力感受器测试）的个体接受了递增肾上腺素输注。在第一个小时内输注生理盐水（0.9%NaCl），然后在第二个和第三个小时内分别输注 0.01μg/kg/min 和 0.03μg/kg/min 的肾上腺素，最后 30 分钟内输注 0.06μg/kg/min。每 30 分钟进行一次高分辨率心电图监测，以测量 QT 间期、心室复极参数（T 波幅度、T 波面积对称比）和血样以测量钾和儿茶酚胺。
NAF 组的基础心率为 68（95%置信区间 60，76）bpm，SAN 组为 73（59，87）bpm，CAN 组为 84（78，91）bpm。在肾上腺素输注期间，各组的心率变化不同（p=0.01）。CAN 组的最大心率增加（95%置信区间）为 22（13，32）bpm，而 NAF 组和 SAN 组分别为 11（7，15）bpm 和 10（3，18）bpm。NAF 组的基础 QT 为 382（95%置信区间 374，390）ms，SAN 组为 378（363，393）ms，CAN 组为 392（367，417）ms（p=0.31）。所有组的 QT 均随肾上腺素输注而延长。最长 QT 为 444（422，463）ms（NAF）、422（402，437）ms（SAN）和 470（402，519）ms（CAN）（p=0.09）。T 波幅度和 T 波对称比降低，并且在 CAN 组中，最大降低发生在较低的输注肾上腺素浓度下，发生时间更早。CAN 组的对称比 AUC 存在差异（p=0.04）。各组的血浆肾上腺素均升高，血钾均降低。
结论/解释：CAN 组的一些参与者在较低的肾上腺素浓度下表现出异常复极。这可能是由于去神经支配的肾上腺素能超敏反应所致。此类个体在应对生理交感肾上腺挑战（如应激或低血糖）时，可能更容易发生心律失常。
