Silke B, Guy S, Riddell J G
University Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Northern Ireland.
J Cardiovasc Pharmacol. 1997 Dec;30(6):817-23. doi: 10.1097/00005344-199712000-00018.
The influence of celiprolol (beta1- and beta2-adrenoceptor partial agonist), propranolol (beta1- and beta2-adrenoceptor antagonist), and atenolol (beta1-adrenoceptor antagonist) on heart-rate variability (HRV) was assessed from Holter records in 12 normal volunteers. A combination of summary statistics and nonlinear procedures was used to assess HRV and autonomic balance. Under double-blind and randomised conditions (Latin-square design), subjects received placebo, celiprolol (200 and 800 mg), propranolol (160 mg), atenolol (50 mg), and combinations of these agents. Single oral doses of medication (at weekly intervals) were administered at 22:30 h with sleeping heart rates (HRs) recorded overnight. Compared with placebo, celiprolol (200 and 800 mg) increased the sleeping HR, the HR effect of celiprolol was different from the bradycardia after propranolol, 160 mg, and atenolol, 50 mg. Dose-response effects on HR with celiprolol were evident in the presence of atenolol, unlike those with propranolol that abolished the HR increase between celiprolol, 200 mg and 800 mg. These data were consistent with beta1-selective adrenoceptor agonism with 200 mg but agonism at both the beta1- and beta2-adrenoceptor with celiprolol, 800 mg. The action of the drugs on short-term HRV indices (rMSSD and pNN50) closely followed their effects on HR. The longer-term HRV indices (global SD, SDANN) were reduced by celiprolol but increased by propranolol and atenolol. At a fixed HR, the data dispersion (SDNN5) was higher with propranolol compared with celiprolol; however, the dispersion was not merely an HR-dependent phenomenon. A novel nonlinear approach (quadrant analysis) revealed the sequencing of cardiac accelerations and decelerations after the high correlation between adjacent intervals had been removed. Celiprolol increased the frequency of consecutive cardiac accelerations; the duration between and variance of these beat-to-beat differences shortened after celiprolol but lengthened with increased variance after propranolol and atenolol. These results demonstrated reduced HRV indices and a shift toward sympathetic dominance after the beta-adrenoceptor agonist celiprolol contrasting with increased HRV indices and parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and atenolol. The implications of these findings for the treatment of patients with cardiovascular disease warrant further study.
在12名正常志愿者中，通过动态心电图记录评估了塞利洛尔（β1和β2肾上腺素能受体部分激动剂）、普萘洛尔（β1和β2肾上腺素能受体拮抗剂）和阿替洛尔（β1肾上腺素能受体拮抗剂）对心率变异性（HRV）的影响。采用汇总统计和非线性程序相结合的方法评估HRV和自主神经平衡。在双盲和随机条件下（拉丁方设计），受试者接受安慰剂、塞利洛尔（200毫克和800毫克）、普萘洛尔（160毫克）、阿替洛尔（50毫克）以及这些药物的组合。单剂量口服药物（每周一次）于22:30给药，并记录过夜睡眠心率（HR）。与安慰剂相比，塞利洛尔（200毫克和800毫克）可提高睡眠心率，塞利洛尔对心率的影响与160毫克普萘洛尔和50毫克阿替洛尔后的心动过缓不同。在阿替洛尔存在的情况下，塞利洛尔对心率的剂量反应效应明显，而普萘洛尔则消除了200毫克和800毫克塞利洛尔之间的心率升高。这些数据与200毫克时的β1选择性肾上腺素能受体激动作用一致，但800毫克塞利洛尔对β1和β2肾上腺素能受体均有激动作用。药物对短期HRV指标（rMSSD和pNN50）的作用与其对心率的影响密切相关。塞利洛尔降低了长期HRV指标（总体标准差、SDANN），而普萘洛尔和阿替洛尔则使其升高。在固定心率下，普萘洛尔的数据离散度（SDNN5）高于塞利洛尔；然而，离散度不仅仅是一种依赖于心率的现象。一种新的非线性方法（象限分析）揭示了在去除相邻间期之间的高相关性后心脏加速和减速的顺序。塞利洛尔增加了连续心脏加速的频率；塞利洛尔后这些逐搏差异的持续时间和方差缩短，但普萘洛尔和阿替洛尔后持续时间延长且方差增加。这些结果表明，与β肾上腺素能受体拮抗剂普萘洛尔和阿替洛尔后HRV指标增加和副交感神经占优势相反，β肾上腺素能受体激动剂塞利洛尔后HRV指标降低且向交感神经占优势转变。这些发现对心血管疾病患者治疗的意义值得进一步研究。
