Li Dingzhou, Chiang Alan Y, Clawson Christine A, Main Bradley W, Leishman Derek J
Global Statistical Sciences and Toxicology, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140, USA.
J Pharmacol Toxicol Methods. 2008 Sep-Oct;58(2):118-28. doi: 10.1016/j.vascn.2008.05.005. Epub 2008 Jul 10.
Adrenergic blockade as a treatment for chronic heart failure (CHF) has proved effective, but its pharmacological mechanism on CHF remains unclear. In the past two decades, studies on heart rate variability (HRV) have reported that CHF patients generally have a reduced temporal complexity in heart rate variability. On the other hand, adrenergic blockers have been shown to restore such complexity. Fractal analysis is a novel and efficient tool to explore the adrenergic blockade effect on HRV. This paper applies the detrended fluctuation analysis (DFA) and multifractal DFA (MF-DFA) methods in an attempt to understand the effect of adrenergic blockade on cardiac dynamics in conscious beagle dogs.
DFA and MF-DFA analysis are conducted on RR interval data generated from telemetry instrumented dogs receiving a combination of 15 mg/kg nadolol and 5 mg/kg phenoxybenzamine orally administered at the 22nd and 34th hour in a parallel design (n=12). All dogs had approximately 48 h of beat-to-beat heart rate measurements recorded in the left ventricle. Complexity measures for heartbeat series are compared between the blocker and vehicle group. We also compute traditional statistics for HRV and spectral parameters and examine their correlation with fractal analysis.
When compared to the vehicle group, the adrenergic blocker group had: 1) longer RR intervals (p=0.02) and lower beat-to-beat variability (p=0.04); 2) decreased low frequency (LF) and high frequency (HF) power (p=0.03), and higher LF-to-HF ratio; 3) larger middle-range scaling exponents (p<0.01); 4) broader multifractal spectra (p=0.03) with higher dominant singularity indices (p=0.02).
Our results show that 1) adrenergic blockade alters the sympathovagal balance; 2) adrenergic blockers enhance the complexity of the cardiac dynamics; 3) the adrenergic blockade effect on cardiac dynamics is primarily the attenuation of small fluctuations in RR intervals. Fractal analysis also has the potential to be applied to early QT diagnosis.
肾上腺素能阻滞剂作为慢性心力衰竭（CHF）的一种治疗方法已被证明是有效的，但其治疗CHF的药理机制仍不清楚。在过去二十年中，关于心率变异性（HRV）的研究报告称，CHF患者的心率变异性时间复杂性通常会降低。另一方面，肾上腺素能阻滞剂已被证明可恢复这种复杂性。分形分析是探索肾上腺素能阻滞剂对HRV影响的一种新颖且有效的工具。本文应用去趋势波动分析（DFA）和多重分形DFA（MF-DFA）方法，试图了解肾上腺素能阻滞剂对清醒比格犬心脏动力学的影响。
对遥测仪器记录的犬在第22小时和第34小时口服15mg/kg纳多洛尔和5mg/kg酚苄明组合药物（平行设计，n = 12）产生的RR间期数据进行DFA和MF-DFA分析。所有犬的左心室均记录了约48小时的逐搏心率测量值。比较阻滞剂组和对照组心跳序列的复杂性指标。我们还计算了HRV的传统统计量和频谱参数，并检查它们与分形分析的相关性。
与对照组相比，肾上腺素能阻滞剂组有：1）RR间期更长（p = 0.02），逐搏变异性更低（p = 0.04）；2）低频（LF）和高频（HF）功率降低（p = 0.03），LF与HF比值更高；3）中程标度指数更大（p < 0.01）；4）多重分形谱更宽（p = 0.03），主导奇异指数更高（p = 0.02）。
我们的结果表明，1）肾上腺素能阻滞剂改变了交感-迷走平衡；2）肾上腺素能阻滞剂增强了心脏动力学的复杂性；3）肾上腺素能阻滞剂对心脏动力学的影响主要是RR间期小波动的衰减。分形分析也有可能应用于早期QT诊断。
