Aronson D, Mittleman M A, Burger A J
Division of Cardiology, RAMBAM Medical Center, Haifa, Israel.
Pacing Clin Electrophysiol. 2001 Nov;24(11):1607-15. doi: 10.1046/j.1460-9592.2001.01607.x.
Endothelin-1 (ET-1) can modulate central and peripheral sympathetic outflow. However, if increased ET-1 levels contribute to autonomic perturbations in the setting of congestive heart failure (CHF) is not known. The purpose of this study was to determine if increased ET-1 levels contribute to the depressed HRV in patients with CHF. Sixty-four patients were admitted to the hospital for treatment of decompensated CHF (mean age 59+/-12 years, NYHA Classes III [72%] and IV [28%]). Time- and frequency-domain HRV measures were obtained from 24-hour Holter recordings. Neurohormonal activation was assessed by measuring plasma renin activity (PRA), aldosterone, norepinephrine, and ET-1 levels. Among the time-domain HRV indices, ET-1 correlated negatively with the standard deviation of RR intervals (SDNN) (r = - 0.38, P = 0.002) and standard deviation of all 5-minute mean RR intervals (SDANN5) (r = - 0.48, P < 0.0001), but not with time-domain indices indicative of parasympathetic modulation. Among the frequency-domain HRV indices, ET-1 correlated negatively with the total power (r = - 0.32, P = 0.01) and ultralow frequency power (ULF) (r = - 0.43, P = 0.0004), but not with indices of parasympathetic (high frequency) or sympathovagal (low frequency) modulation. Using multiple linear regression, adjusting for clinical parameters, drug therapies, and other neurohormones, the strong negative relationship between ET-1 and SDNN (P = 0.027), SDANN5 (P = 0.002), and ULF power (P = 0.017) persisted. In conclusion, ET-1 may play an important role in the autonomic dysfunction characteristic of CHF. The correlation between ET-1 levels and prognostically important indices of overall HRV suggests that these HRV measures are better markers of neurohormonal activation in CHF, which may partially account for their greater discriminatory power for risk stratification.
内皮素-1（ET-1）可调节中枢和外周交感神经输出。然而，ET-1水平升高是否会导致充血性心力衰竭（CHF）患者出现自主神经功能紊乱尚不清楚。本研究的目的是确定ET-1水平升高是否会导致CHF患者心率变异性（HRV）降低。64例因失代偿性CHF入院治疗的患者（平均年龄59±12岁，纽约心脏协会III级[72%]和IV级[28%]）。从24小时动态心电图记录中获取时域和频域HRV测量值。通过测量血浆肾素活性（PRA）、醛固酮、去甲肾上腺素和ET-1水平来评估神经激素激活情况。在时域HRV指标中，ET-1与RR间期标准差（SDNN）呈负相关（r = -0.38，P = 0.002），与所有5分钟平均RR间期标准差（SDANN5）呈负相关（r = -0.48，P < 0.0001），但与指示副交感神经调节的时域指标无关。在频域HRV指标中，ET-1与总功率（r = -0.32，P = 0.01）和超低频功率（ULF）呈负相关（r = -0.43，P = 0.0004），但与副交感神经（高频）或交感迷走神经（低频）调节指标无关。使用多元线性回归，在调整临床参数、药物治疗和其他神经激素后，ET-1与SDNN（P = 0.027）、SDANN5（P = 0.002）和ULF功率（P = 0.017）之间的强负相关关系依然存在。总之，ET-1可能在CHF特征性的自主神经功能障碍中起重要作用。ET-1水平与总体HRV的预后重要指标之间的相关性表明，这些HRV测量值是CHF中神经激素激活的更好标志物，这可能部分解释了它们在风险分层方面具有更大的鉴别能力。
