Yeragani Vikram Kumar, Tancer Manuel, Uhde Thomas
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
Psychiatry Res. 2003 Dec 1;121(2):185-96. doi: 10.1016/s0165-1781(03)00235-x.
Anxiety disorders are associated with an increase in cardiovascular mortality. Studies using heart rate (HR) and QT interval variability measures suggest a decreased cardiac vagal function and a relatively increased sympathetic function in anxiety. This is important, as increased sympathovagal balance is associated with life-threatening arrhythmias. Several studies have shown that panic disorder is associated with an increased sensitivity to yohimbine and a blunted growth hormone response to clonidine, which are alpha-2 adrenoceptor antagonist and agonist, respectively. This study investigated the changes in QTvi (QT variance corrected for mean QT interval squared/HR variance corrected for mean HR squared) during placebo, oral clonidine (150 mg) and oral yohimbine (20 mg) in a double-blind design in 12 normal controls and 19 patients with panic disorder. HR and QT variability measures, especially QTvi, were obtained before and after the administration of these drugs to patients in supine and standing postures. As expected, patients with panic disorder became more anxious after yohimbine. In addition, the patients had a significant increase in QTvi after yohimbine and a significant decrease in QTvi after clonidine, which was not seen in the control group. The decreased anxiety after placebo was associated with decreased QTvi in patients. This study supports the previous reports of an abnormal sensitivity of alpha-2 adrenergic receptors in patients with panic disorder compared to controls and partly explains the association of increased cardiovascular mortality with conditions of anxiety. QTvi, a non-invasive indicator of cardiac repolarization lability, appears to be a useful tool to study cardiac sympathetic function.
焦虑症与心血管疾病死亡率的增加有关。使用心率（HR）和QT间期变异性测量的研究表明，焦虑症患者心脏迷走神经功能下降，交感神经功能相对增强。这一点很重要，因为交感迷走神经平衡的增加与危及生命的心律失常有关。多项研究表明，惊恐障碍与对育亨宾的敏感性增加以及对可乐定的生长激素反应迟钝有关，育亨宾和可乐定分别是α-2肾上腺素能受体拮抗剂和激动剂。本研究采用双盲设计，对12名正常对照者和19名惊恐障碍患者在服用安慰剂、口服可乐定（150毫克）和口服育亨宾（20毫克）期间的QTvi（QT方差校正为平均QT间期平方/HR方差校正为平均HR平方）变化进行了研究。在患者仰卧和站立姿势下，于给药前后测量HR和QT变异性指标，尤其是QTvi。正如预期的那样，惊恐障碍患者在服用育亨宾后变得更加焦虑。此外，患者在服用育亨宾后QTvi显著增加，服用可乐定后QTvi显著降低，而对照组未出现这种情况。安慰剂治疗后焦虑减轻与患者QTvi降低有关。本研究支持了先前的报道，即与对照组相比，惊恐障碍患者的α-2肾上腺素能受体存在异常敏感性，部分解释了心血管疾病死亡率增加与焦虑状态之间的关联。QTvi作为心脏复极易损性的非侵入性指标，似乎是研究心脏交感神经功能的有用工具。
