Jacob G, Shannon J R, Costa F, Furlan R, Biaggioni I, Mosqueda-Garcia R, Robertson R M, Robertson D
Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Circulation. 1999 Apr 6;99(13):1706-12. doi: 10.1161/01.cir.99.13.1706.
Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses.
Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups.
The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.
慢性直立不耐受（OI）的特征是站立时脑灌注不足的症状，且不存在明显的直立性低血压。典型表现为心率增加≥30次/分钟。可能的潜在病理生理机制包括血容量不足、部分自主神经功能障碍或原发性高肾上腺素能状态。我们检验了OI患者在调节心血管反应的自主神经元中存在功能异常这一假设。
13例慢性OI患者和10例对照受试者接受了一系列自主神经测试。在给予酪胺前后，分别于患者仰卧位和站立位测定全身去甲肾上腺素（NE）动力学。此外，还测定了压力反射敏感性、对肾上腺素能激动剂推注的血流动力学反应以及固有心率。两组患者仰卧位静息时的NE溢出量和清除率相似。站立时，患者的NE清除率下降幅度大于对照受试者（55±5%对30±7%，P<0.02）。给予酪胺后，患者的NE溢出量无显著变化，而对照受试者增加了50±10%（P<0.001）。使患者心率增加25次/分钟所需的异丙肾上腺素剂量低于对照受试者（0.5±0.05对1.0±0.1微克，P<0.005），使患者收缩压升高25毫米汞柱所需的去氧肾上腺素剂量低于对照受试者（105±11对
