Ferguson D W, Berg W J, Sanders J S, Roach P J, Kempf J S, Kienzle M G
Department of Internal Medicine, University of Iowa Hospitals, Iowa City.
Circulation. 1989 Jul;80(1):65-77. doi: 10.1161/01.cir.80.1.65.
Digitalis glycosides exert both excitatory and inhibitory autonomic actions in animals and produce vasoconstriction in normal humans but produce vasodilation in heart failure patients. To determine whether or not these contrasting vascular responses are due to differing autonomic actions of the drug, we compared the responses to intravenous administration of Cedilanid-D (0.02 mg/kg) in eight normal subjects (mean age, 23 +/- 1 years) and eight patients with moderate-to-severe heart failure (mean age, 52 +/- 5 years, NYHA Class III-IV). Hemodynamics and efferent sympathetic nerve activity to muscle (MSNA) were measured during 5-minute periods before (control) and 20 minutes after drug administration. In the heart failure patients, Cedilanid-D significantly increased systolic and pulse pressures, whereas mean arterial pressure was unchanged. There was a decrease in right atrial pressure and a tendency for a decrease in pulmonary artery diastolic pressure with a slowing of heart rate. Cardiac index increased by 24 +/- 7%. Short-term administration of digitalis in these heart failure patients produced a fall in forearm vascular resistance (from 37.6 +/- 8.2 to 31.8 +/- 8.1 units, p less than 0.05) and an early, profound, and sustained decrease in MSNA (from 831.0 +/- 118.4 to 474.4 +/- 103.6 units/100 heart beats, p less than 0.01). Digitalis glycosides produced different vascular and MSNA responses in the normal subjects. In the normal volunteers, the drug significantly increased systolic, mean, and pulse pressures and decreased central venous pressure and heart rate. Despite the significant increase in arterial pressure, there was no change in forearm vascular resistance (from 11.7 +/- 1.0 to 12.7 +/- 1.0 units, p = NS) or MSNA (from 494.8 +/- 88.5 to 369.1 +/- 60.5 units/100 heart beats, p = NS), suggesting a sympathoexcitatory response in normal subjects. To determine whether or not the digitalis-induced sympathoinhibition in the heart failure patients was simply due to an inotropic effect (stimulation of inhibitory cardiac mechanoreceptors), we studied the responses of seven additional patients with heart failure before and during administration of dobutamine (3.4 +/- 0.4 micrograms/kg/min). Dobutamine produced a 34 +/- 3% increase in cardiac index, no significant change in systemic arterial pressures, a decrease in pulmonary artery diastolic and right atrial pressures, and no change in heart rate or forearm vascular resistance (from 30.2 +/- 4.3 to 26.5 +/- 4.7 units, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)
洋地黄糖苷在动物体内既有兴奋性又有抑制性自主神经作用，在正常人中可引起血管收缩，但在心力衰竭患者中则引起血管舒张。为了确定这些截然不同的血管反应是否归因于该药物不同的自主神经作用，我们比较了8名正常受试者（平均年龄23±1岁）和8名中重度心力衰竭患者（平均年龄52±5岁，纽约心脏协会心功能分级III - IV级）静脉注射西地兰 - D（0.02mg/kg）后的反应。在给药前（对照）的5分钟期间以及给药后20分钟测量血流动力学和肌肉传出交感神经活动（MSNA）。在心力衰竭患者中，西地兰 - D显著升高收缩压和脉压，而平均动脉压未改变。右心房压力降低，肺动脉舒张压有降低趋势，心率减慢。心脏指数增加了24±7%。在这些心力衰竭患者中短期给予洋地黄导致前臂血管阻力下降（从37.6±8.2降至31.8±8.1单位，p<0.05），并且MSNA早期、显著且持续降低（从831.0±118.4降至474.4±103.6单位/100次心跳，p<0.01）。洋地黄糖苷在正常受试者中产生了不同的血管和MSNA反应。在正常志愿者中，该药物显著升高收缩压、平均动脉压和脉压，并降低中心静脉压和心率。尽管动脉压显著升高，但前臂血管阻力（从11.7±1.0升至12.7±1.0单位，p =无统计学意义）或MSNA（从494.8±88.5降至369.1±60.5单位/100次心跳，p =无统计学意义）没有变化，提示正常受试者中有交感神经兴奋反应。为了确定心力衰竭患者中洋地黄诱导的交感神经抑制是否仅仅是由于正性肌力作用（刺激抑制性心脏机械感受器），我们研究了另外7名心力衰竭患者在给予多巴酚丁胺（3.4±0.4μg/kg/min）之前和期间的反应。多巴酚丁胺使心脏指数增加34±3%，全身动脉压无显著变化，肺动脉舒张压和右心房压力降低，心率和前臂血管阻力无变化（从30.2±4.3降至26.5±4.7单位，p =无统计学意义）。（摘要截断于400字）
