Jacob G, Shannon J R, Black B, Biaggioni I, Mosqueda-Garcia R, Robertson R M, Robertson D
Clinical Research Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn 37232-2195, USA.
Circulation. 1997 Jul 15;96(2):575-80. doi: 10.1161/01.cir.96.2.575.
Idiopathic orthostatic tachycardia (IOT) is characterized by an increase in heart rate (HR) with standing of > or = 30 bpm that is associated with elevated catecholamine levels and orthostatic symptoms. A dynamic orthostatic hypovolemia and alpha1-adrenoreceptor hypersensitivity have been demonstrated in IOT patients. There is evidence of an autonomic neuropathy affecting the lower-extremity blood vessels.
We studied the effects of placebo, the alpha1-adrenoreceptor agonist midodrine (5 to 10 mg), the alpha2-adrenoreceptor agonist clonidine (0.1 mg), and I.V. saline (1 L) in 13 patients with IOT. Supine and upright blood pressure (BP) and HR were measured before and at 1 and 2 hours after intervention. Midodrine decreased both supine and upright HR (all HR values are given as bpm) at 2 hours (from 78+/-2 supine to 108+/-5 upright before treatment and from 69+/-2 supine to 95+/-5 upright after treatment, P<.005 for supine and P<.01 for upright). Saline decreased both supine and upright HR (from 80+/-3 supine to 112+/-5 upright before infusion and from 77+/-3 supine to 91+/-3 upright 1 hour after infusion, P<.005 for supine and P<.001 for upright). Clonidine decreased supine HR (from 78+/-2 to 74+/-2, P<.03) but did not affect the HR increase with standing. Clonidine very significantly decreased supine systolic BP (from 109+/-3 at baseline to 99+/-2 mm Hg at 2 hours, P<.001), and midodrine decreased supine systolic BP mildly.
IOT responds best acutely to saline infusion to correct the underlying hypovolemia. Chronically, this can be accomplished with increased salt and water intake in conjunction with fludrocortisone. The response of patients to the alpha1-agonist midodrine supports the hypothesis of partial dysautonomia and indicates that the use of alpha1-agonists to pharmacologically replace lower-extremity postganglionic sympathetics is an appropriate overall goal of therapy. These findings are consistent with our hypothesis that the tachycardia and elevated catecholamine levels associated with IOT are principally due to hypovolemia and loss of adequate lower-extremity vascular tone.
特发性直立性心动过速（IOT）的特征是站立时心率（HR）增加≥30次/分钟，这与儿茶酚胺水平升高和直立性症状有关。IOT患者已证实存在动态性直立性血容量不足和α1 -肾上腺素能受体超敏反应。有证据表明自主神经病变影响下肢血管。
我们研究了安慰剂、α1 -肾上腺素能受体激动剂米多君（5至10毫克）、α2 -肾上腺素能受体激动剂可乐定（0.1毫克）和静脉输注生理盐水（1升）对13例IOT患者的影响。在干预前以及干预后1小时和2小时测量仰卧位和直立位血压（BP）及心率。米多君在2小时时降低了仰卧位和直立位心率（所有心率值均以次/分钟为单位）（治疗前仰卧位心率为78±2次/分钟，直立位为108±5次/分钟；治疗后仰卧位为69±2次/分钟，直立位为95±5次/分钟，仰卧位P<0.005，直立位P<0.01）。生理盐水降低了仰卧位和直立位心率（输注前仰卧位心率为80±3次/分钟，直立位为112±5次/分钟；输注后1小时仰卧位为77±3次/分钟，直立位为91±3次/分钟，仰卧位P<0.005，直立位P<0.001）。可乐定降低了仰卧位心率（从78±2次/分钟降至74±2次/分钟，P<0.03），但不影响站立时心率的增加。可乐定非常显著地降低了仰卧位收缩压（从基线时的109±3毫米汞柱降至2小时时的99±2毫米汞柱，P<0.001），米多君轻度降低了仰卧位收缩压。
IOT对输注生理盐水以纠正潜在的血容量不足反应最佳。长期而言，可通过增加盐和水的摄入量并联合使用氟氢可的松来实现。患者对α1 -激动剂米多君的反应支持了部分自主神经功能异常的假说，并表明使用α1 -激动剂从药理学上替代下肢节后交感神经是合适的总体治疗目标。这些发现与我们的假说一致，即与IOT相关的心动过速和儿茶酚胺水平升高主要是由于血容量不足和下肢血管张力不足所致。
