The acute effects of inhaled salbutamol on the beat-to-beat variability of heart rate and blood pressure assessed by spectral analysis

Aims We wanted to study the effects of a 600  μg inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma.
Methods In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20  min and 2  h after the drug inhalation. The R–R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis.
Results Salbutamol significantly decreased the total and low frequency (LF) variability of R–R intervals as well as the high frequency (HF) variability of R–R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R–R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation.
Conclusions We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.     

Effect of cardiac vagal outflow on complexity and fractal correlation properties of heart rate dynamics

1. Cardiac vagal outflow is the major factor determining the magnitude of heart rate (HR) variability analysed by traditional time and frequency domain methods. New analysis techniques, such as fractal and complexity methods, have been developed to probe non-linear features in HR behaviour that may not be detectable by traditional methods. 2. We investigated the effects of vagal blockade (glycopyrrolate i.v. 5 microg kg-1 h-1 for 2 h, n = 8 vs. unmedicated control group, n = 8) and various breathing patterns (n = 12) on two non-linear measures of HR variability--detrended fluctuation analysis (DFA) and approximate entropy (ApEn)--in healthy male volunteers. 3. Glycopyrrolate decreased the mean (+/-SD) ApEn from 1.46 +/- 0.18 to 0.85 +/- 0.24 (P = 0.001 in comparison with the control group), and increased the short-term (alpha 1) and intermediate-term (alpha 2) fractal scaling exponents of DFA, alpha 1 from 0.96 +/- 0.19 to 1.43 +/- 0.29 (P = 0.003) and alpha 2 from 1.13 +/- 0.10 to 1.34 +/- 0.14 (P < 0.001). 4. Decrease in fixed respiration rate from 15 to 6 breaths min-1 increased alpha 1 from 0.83 +/- 0.25 to 1.18 +/- 0.27 (P < 0.001), but decreased alpha 2 from 0.88 +/- 0.09 to 0.45 +/- 0.17 (P < 0.001) and ApEn from 1.26 +/- 0.12 to 1.10 +/- 0.14 (P = 0.028). Rapid breathing (24 min-1) had no influence on these non-linear measures of HR variability. Hyperventilation (15 min-1, tidal volume increased voluntarily by 0.5 l) decreased alpha 1 from 0.83 +/- 0.25 to 0.66 +/- 0.28 (P = 0.002) but did not affect alpha 2 or ApEn. 5. To conclude, vagal blockade alters the fractal scaling properties of R-R intervals (alpha 1, alpha 2) and reduces the complexity (ApEn) of HR behaviour. Both the fractal and complexity measures of HR variability can also be influenced by changes in the breathing pattern.     

Effects of atropine on the time and frequency domain estimates of blood pressure and heart rate variability in mice

1. Indices quantifying blood pressure (BP) and heart rate (HR) variability have been recently developed and may be used to assess the contribution of the autonomic nervous system to cardiovascular fluctuations. 2. Cardiovascular variables were measured in eight conscious mice equipped with a BP telemetric device. Each recording session was conducted when the mice were at rest and included a control period, an injection of atropine methylnitrate (2 mg/kg) and a post-treatment recording. 3. Time domain indices were the mean pulse interval (PI) and NN (the normal-to-normal intervals), mean HR, standard deviation of PI (SDNN), the square root of the mean of the sum of the squares of differences between adjacent PI (RMSSD) and the pNN8 (NN8 count divided by the number of NN intervals). Frequency domain indices of HR variability were the low frequency (LF) zone (0.15-0.60 Hz) and the high frequency (HF, respiratory sinus arrhythmia) zone (2.5-5.0 Hz) of the PI power spectrum. The time domain index of spontaneous baroreflex sensitivity (BRS) was the slope of the linear PI and systolic BP relationship obtained using the sequence technique. The frequency domain indices of BRS were the gain of the transfer function between systolic BP and PI in the LF and HF bands. 4. Atropine markedly affected these variables, illustrating vagal predominance under resting conditions in mice. The preferable time and frequency domain indices for quantifying the vagal contribution to HR variability were the pNN8 and the LF gain.     

针刺治疗对原发性高血压患者血压变异性和心率变异性的影响

目的：探讨针刺治疗对原发性高血压患者血压变异性和心率变异性的影响。方法选择符合条件的60例原发性高血压患者进行针刺治疗,疗程为30 d,采用自身前后对照,分别于治疗前后完善24 h动态血压及24 h动态心电图检查。结果针刺治疗后血压变异性各指标（24 h平均收缩压、24 h平均舒张压、24 h收缩压标准差、24 h舒张压标准差、白昼收缩压标准差、白昼舒张压标准差、夜间收缩压标准差、夜间舒张压标准差）均较治疗前降低,差异具有统计学意义（ P＜0．05）;心率变异性各指标（连续RR间期标准差、平均5 min RR间期标准差、平均5 min RR间期标准差的平均值、连续RR间期差值的均方根值、相邻RR间期大于50 ms的百分数）均较治疗前有所改善,差异具有统计学意义（ P＜0．05）。结论针刺治疗能显著降低原发性高血压患者的血压变异性,改善心率变异性,从而可能改善高血压患者的靶器官损害。     

Effects of autonomic blockade on non-linear cardiovascular variability indices in rats

1. The present study assesses the effects of autonomic blockade (alpha- and beta-adrenoceptor and cholinergic) on cardiovascular function studied by heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity in rats using non-linear dynamics. Little is known about the influence of pharmacological autonomic nervous system interventions on non-linear cardiovascular regulatory indices. 2. In 13 conscious rats, heart rate and aortic blood pressure were measured continuously before, during and after autonomic blockade with atropine, phentolamine and propranolol. Non-linear scaling properties were studied using 1/f slope, fractal dimension and long- and short-term correlation. Non-linear complexity was described with correlation dimension, Lyapunov exponent and approximate entropy. Non-linear indices were compared with linear time and frequency domain indices. 3. Beta-adrenoceptor blockade did not alter the non-linear characteristics of HRV and BPV, although low-frequency power of HRV was depressed. Alpha-adrenoceptor blockade decreased the scaling behaviour of HRV, whereas cholinergic blockade decreased the complexity of the non-linear system of HRV. For BPV, the scaling behaviour was increased during alpha-adrenoceptor blockade and the complexity was increased during cholinergic blockade. The linear indices of HRV and BPV were decreased. 4. The present results indicate that the beta-adrenoceptor system has little involvement in the generation of non-linear HRV and BPV in rats. 5. Alpha-adrenoceptor blockade mostly influenced the scaling properties of the time series, whereas cholinergic blockade induced changes in the complexity measures. 6. The absence of the baroreflex mechanism can trigger a compensatory feed-forward system increasing the complexity of BPV.     

The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone

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高血压患者心率变异性与血压变异性分析

目的 分析高血压患者心率变异性与血压变异性的关系.方法 对高血压患者120例按1999年WHO/ISH高血压诊断标准分为:1级高血压40例,2级高血压40例,3级高血压40例,另设正常血压对照组40例,均同时检测心率变异性与血压变异性.结果 各组间心率变异性差异有统计学意义(P<0.05或P<0.01),随组间血压增高,心率变异性趋向减少;各组间血压变异性差异有统计学意义(P<0.01),随组间血压增高,血压变异性趋向增大.结论 高血压患者血压分级与心率变异性和血压变异性有一定关系.     

Effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension

AIMS: The aim of the present study was to evaluate the effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension. METHODS: Ten inpatients with mild to moderate essential hypertension (four men and six women; age: 44-64 years) underwent a drug-free period for 7 days and a treatment period with cilnidipine 10 mg orally for another 7 days, in a randomized crossover study. On the sixth day of each period, they underwent autonomic function tests including a mental arithmetic test, a cold pressor test and a Valsalva manoeuvre. After these tests, 24 h ambulatory blood pressure, heart rate, and the electrocardiogram R-R intervals were monitored every 30 min. A power spectral analysis of R-R intervals was performed to obtain the low-and high-frequency components. RESULTS: Cilnidipine significantly decreased the 24 h blood pressure by 6.5 +/- 1.7 mm Hg systolic (mean +/- s.e.mean; P < 0.01) and 5.0 +/- 1.1 mmHg diastolic (P < 0.01), whereas cilnidipine did not change heart rate or any indices of power spectral components. During the cold pressor test, the maximum change in systolic blood pressure and percentage changes in both systolic and diastolic blood pressures were significantly lower during the treatment period with cilnidipine than during the drug-free period. The baroreflex sensitivity measured from the overshoot phase of the Valsalva manoeuvre did not differ significantly between the two periods. CONCLUSIONS: Cilnidipine is effective as a once-daily antihypertensive agent and causes little influence on heart rate and the autonomic nervous system in patients with mild to moderate essential hypertension. Moreover, it is suggested that cilnidipine has an additional clinical benefit in the inhibition of the pressor response induced by acute cold stress.     

艾塞那肽对糖尿病自主神经病变患者氧化应激状态、血糖水平及心率变异性的影响

目的 探讨艾塞那肽对糖尿病自主神经病变（DAN）患者氧化应激、血糖及心率变异性的影响。方法 选取2015年4月—2017年4月在北京航天总医院治疗的DAN患者128例,根据患者最终选取的治疗方案分为观察组（n=67）和对照组（n=61）,对照组给予常规糖尿病治疗方案,观察组在对照组基础上给予sc艾塞那肽,2次/d,5 μg/次,总疗程12周。观察两组患者氧化应激、血糖及心率变异性情况。结果 观察组治疗后餐后2 h血糖（2h-PG）、糖化血红蛋白（HbA1c）和体质量指数（BMI）分别为（7.02±1.37）mmol/L、（6.71±1.82）%和（24.89±1.03）kg/m²,均显著低于对照组（P<0.05）。观察组治疗后丙二醛（MDA）、同型半胱氨酸（Hcy）分别为（2.51±0.91）mol/L和（12.03±3.11）μmmol/L,均显著低于对照组（P<0.05）,而超氧化物歧化酶（SOD）为（37.10±5.03）mU/L,显著高于对照组（P<0.05）。观察组治疗后总体标准差（SDNN）、差值均方的平方根（RMSSD）、爱丁堡指数（PNN50）、极频（VLF）、低频（LF）、高频（HF）分别为（50.25±8.10）ms、（26.02±5.55）ms、（12.01±1.32）%、（86.02±8.22）ms²、（71.14±7.05）ms²、（42.10±8.33）ms²,均显著高于对照组（P<0.05）,而LF/HF为（1.72±0.48）,显著低于对照组（P<0.05）。结论 艾塞那肽能有效控制DAN患者血糖,改善患者BMI和心率变异指标,减轻氧化应激反应。     

Effect of cold on fetal heart rate and its variability

1. The effects of cold saline (25 mL) injected over the fetal skin on fetal heart rate (HR) and HR variability (HRV), measured as the coefficient of variation (CV) in pulse interval (PI) and by power spectral analysis (PSA), were measured in 10 chronically catheterized fetal sheep aged 140-144 days. To determine the extent to which effects on HR and HRV were mediated by the sympathoadrenal neuroendocrine axis and the cardiac vagus, experiments were performed before and after beta-adrenoreceptor blockade with propranolol (n = 12 fetuses) or before and after cardiac vagal blockade with atropine (n = 4 fetuses). 2. Injection of ice-cold saline over the skin caused an immediate rise in mean arterial pressure (MAP) from 46+/-1 to 55+/-1 mmHg (P < 0.001) and HR from 156+/-2 to 182+/-2 b.p.m. (P < 0.001). Heart rate variability, measured as CV of PI, rose from 3.5+/-0.2 to 8.0+/-0.2% (P < 0.001) and total power spectral density (PSD) increased from 78+/-6 to 278+/-16 units (P < 0.001) as measured by PSA. Within 100s, MAP, HR and HRV had returned to baseline. 3. Beta-adrenoreceptor blockade abolished all these changes in HR, HRV and PSD, but had no effect on changes in MAP. Atropine had no demonstrable effect on the responses to cold. 4. Therefore, the increase in fetal MAP, HR and HRV that occurred with stimulation of peripheral thermoreceptors was the result of increased activity of the sympathetic nervous system. Alterations in efferent cardiac vagal tone were not involved in the cardiac response to cold.     

血压及心率变异性对急性心肌梗死后患者预后价值的研究

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The effect of continuous positive airway pressure on heart rate variability during the night in patients with chronic heart failure and central sleep apnoea

Continuous positive airway pressure (CPAP) improves autonomic activity in patients with chronic heart failure (CHF) and central sleep apnoea (CSA), but its effect on heart rate variability (HRV) during therapy has not been reported. We hypothesized that CPAP may decrease HRV, despite its beneficial effects on sympathetic overactivation, due to the expected stabilization of breathing. Sixty‐seven CHF patients underwent polysomnography (PSG). Ten of them presented with CSA (age 66.1±8.5 years, apnoea‐hypopnea index [AHI]=57.6±23.3, central AHI [cAHI]=41.6±24.6 [mean±SD]) and were subjected to a second PSG with manual CPAP titration. Beat‐to‐beat heart intervals for a 6‐hour period of sleep were extracted from each recording and HRV was analysed. CPAP significantly reduced AHI (AHI=23.1±18.3 P=.004). Standard deviation of normal‐normal interbeat interval (SDNN) (61.5±29.0 vs 49.5±19.3 ms, P=.021), root mean square of successive differences (RMSSD) (21.8±9.2 vs 16.4±7.1 ms, P=.042), total power (lnTP=7.8±1.1 vs 7.4±0.8 ms², P=.037), low frequency power (lnLF=5.5±1.5 vs 5.0±1.4 ms², P=.003) and high frequency power (lnHF=4.6±1.0 vs 4.0±1.0 ms², P=.024) were decreased. There was a strong correlation between the decrease in AHI and the decrease in lnHF (Spearman's ρ=.782). CPAP leads to a decrease in spectral and time domain parameters of HRV during therapy in CHF patients with CSA. These changes are best explained by the effect which CPAP‐influenced breathing pattern and lowered AHI exert on HRV.     

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充血性心力衰竭患者动态血压变异与预后的相关性研究

目的:探讨充血性心力衰竭患者的动态血压变异与其预后的关系。方法:共纳入80例各种原因心衰入院患者,入院后均常规行超声心动图检查和动态血压检查。然后通过电话或者门诊随访其心源性死亡事件的发生。结果:夜间舒张压变异(DSD)和左室射血分数(LVEF)是心衰患者心源性死亡的独立影响因素。结论:血压变异是充血性心力衰竭患者预后的独立影响因素;可以用其预测心衰患者心源性死亡。     

伊贝沙坦对原发性高血压的疗效及心率变异性的影响

目的 :观察伊贝沙坦对原发性高血压 (EH)的疗效及心率变异性的变化。方法 :原发性高血压患者 40例每日口服伊贝沙坦 1 5 0～ 3 0 0mg,共 8wk。观察血压变化 ,记录用药前后 2 4h动态心电图 ,分析心率变异 (HRV)时域和频域指标 ,并与 3 5例健康对照组比较。结果 :①EH患者应用伊贝沙坦后收缩压 (SBP)和舒张压 (DBP)由 2 1 .62± 0 .47/1 2 .0 1±0 .3 2kPa分别下降至 1 8.9± 0 .3 2 /8.0 1± 2 .3 5kPa,有效率达 73 .1 %。②与对照组相比 ,EH患者相邻正常RR间期标准差 (SDNN) ,正常相邻RR间期差值 (RMSSD) ,相邻正常RR间期差值大于 5 0ms的窦性心律 (PNN50 ) ,高频功率 (HF)明显下降 ,低频功率(LF)不变 ,低频功率 /高频功率 (LF/HF)值增加。应用伊贝沙坦后 ,SDNN、RMSSD、PNN50 、HF增加 ,LF/HF值降低。结论 :原发性高血压患者存在HRV下降 ,而伊贝沙坦在有效降低血压同时提高HRV ,改善自主神经功能失衡。     

Effect of chronic intermittent hypobaric hypoxia on heart rate variability in conscious rats

To examine the effect of chronic intermittent hypobaric hypoxia (CIHH) on heart rate variability (HRV), male adult Sprague Dawley rats were exposed to hypoxia (oxygen 11.1%) in a hypobaric chamber for 42 days, 6 hours each day, simulating an altitude of 5000 m. The body weight and blood pressure of rats were recorded once a week, electrocardiograms were analyzed continuously using biotelemetry, before, during and after CIHH treatment each day, and HRV was evaluated using spectrum analysis. No significant difference of body weight and blood pressure was found between CIHH and control rats. After 4 weeks of CIHH treatment, total power (TP) and very low-frequency component (VLF) were lower in CIHH rats than in control rats under hypobaric hypoxia condition. During CIHH treatment, low frequency (LF) was higher in 1 week and lower in 5–6 weeks in CIHH rats than control rats under hypobaric hypoxia, but not normoxic conditions. The high-frequency component (HF) was not changed during CIHH treatment, so LF/HF increased initially, and then recovered under the hypobaric hypoxia condition following 3 weeks of CIHH treatment. In addition, the HR was increased in CIHH rats after 4 weeks of CIHH treatment compared with control rats. Furthermore, HRV was altered significantly in control rats, but not in CIHH rats exposed to acute normobaric hypoxia. These data suggest that CIHH treatment modulates cardiac autonomic activity adaptively and inhibits the acute normobaric hypoxia-induced changes in HRV.     

冠心病患者心率变化、血压与心肌缺血改变的相关性研究

目的根据监测清晨血压变化参数与对应时域的缺血ST段演变相关性,探讨冠心病合并高血压患者心率变化、血压是否与心肌缺血改变存在相关性。方法对2010年2月～2011年2月90例冠心病合并高血压患者（高血压组）及66例单纯冠心病患者（对照组）,行24h动态心电图及同步动态血压监测,获得的心率、清晨血压波动值和ST段压低持续时间进行相关性统计学分析及研究结论。结果高血压组的清晨血压升值与对应时域的ST段压低有正相关性关系;尤以清晨血压回升差值（收缩压、平均脉压、舒张压）和心率与对应ST段压低有显著正相关性,而对照组无明显相关性。结论清晨清醒前后血压升高与心肌缺血的发生呈正相关关系,且多为无痛性心肌缺血。     

不同短时收缩压变异性指标与老年人群肾小球滤过率的关系

摘要： 目的 探讨不同短时收缩压变异性 （SBPV） 指标与老年人群肾小球滤过率 （eGFR） 的关系。方法 在参加开滦研究队列第3次健康体检的人群中, 采取整群抽样的方法随机抽取年龄≥60岁的开滦集团离退休员工进行24 h 动态血压监测等检查。在抽取的 3 064 例观察对象中, 符合入选标准 2 464 例, 最终纳入统计分析 1 405 例。SBPV 采用标准差 （SD）、 独立变异性 （VIM）、 极差 （MMD） 和平均真实变异性 （ARV） 4 种指标。采用多因素逐步线性回归分析不同短时 SBPV 指标与 eGFR 的关联。结果 （1） 在 1 405 例观察对象中, 平均年龄 （67.16±5.82） 岁, 其中男 933 例 （66.4%）, 女 472 例 （33.6%）。（2） 将 24 h、 日间、 夜间平均收缩压 （SBP） 进行四分类 （<120 mmHg 为第一分类组, 120 mmHg≤平均 SBP<140 mmHg 为第二分类组, 140 mmHg≤平均 SBP<160 mmHg 为第三分类组, 平均 SBP≥160 mmHg 为第四分类组）, 结果显示, 除 VIM 外, 随着平均 SBP 的增加, 其他短时 SBPV 指标 （SD、 MMD、 ARV） 均呈上升趋势。（3） 取 24 h、 日间、 夜间 SBPV 中位数 （P50 ） 分组, 高分位组的 eGFR 水平均低于低分位组, 除夜间 VIM 组外, 组间差异均有统计学意义。（4） 回归分析结果显示, eGFR 随着 24 h SBPV 指标 （SD、 MMD、 ARV）、 日间 SBPV 指标 （MMD、 ARV）的增加而降低 （标准化β分别为 -0.07、 -0.11、 -0.07, -0.12、 -0.07）, 夜间 SBPV 指标均对 eGFR 无影响。结论 不同短时 SBPV 指标与eGFR 存在一定程度的关联。     

Analysis of rapid heart rate variability in the assessment of anticholinergic drug effects in humans

Anticholinergic agents have widespread therapeutic indications in clinical medicine. In addition, certain other drug groups–such as neuroleptics, antidepressants and antihistamines–possess distinct anticholinergic properties that reduce tolerance and compliance. Especially in patients with heart disease, attention should be paid to cardiac anticholinergic drug effects. The analysis of short-term heart rate variability (HRV) provides a noninvasive tool to estimate vagal cholinergic outflow. In this review article, we present the basic principles of the most relevant techniques to study rapid HRV: the time domain analysis methods RMSSD and pNN50, and the high-frequency (HF) spectral component of HRV. We provide examples of previously reported effects of anticholinergic agents on these measures and also describe how adrenergic drugs may influence them. We have the following recommendations for a clinical pharmacologist investigating anticholinergic agents. (1) If the breathing rate of the study subject can be controlled during the assessment and the electrocardiogram recordings contain good-quality, stationary segments that are at least a few minutes long, then the HF power of HRV should be the method of choice. (2) During uncontrolled conditions, RMSSD should be included in the analyses, because it is less affected by changes in the respiratory pattern and it can be measured from shorter segments of electrocardiogram data. (3) Reduced short-term HRV suggests an anticholinergic, but not necessarily an antimuscarinic drug effect, since the inhibition of cholinergic vagal efferent activity may also originate from central or peripheral adrenergic influences.     

Lack of association between QT dispersion and blood pressure response during dental surgery

1. It is well known that dental surgery induces increases in blood pressure. However, the factors influencing this increase are not yet fully understood. We have determined the relationship between QTc (= QT/RR(1/2), with RR being the R-R interval in seconds) dispersion, measured with a 12-lead surface electrocardiogram, and changes in blood pressure during tooth extraction. 2. Both QTc dispersion and the power spectrum of R-R variability were determined before the dental surgery was undertaken. The low-frequency (LF; 0.041-0.140 Hz), high- frequency (HF; 0.140-0.500 Hz) and total spectral powers (TF; 0.000-4.000 Hz) were calculated and the ratio of LF to HF and the percentage of HF relative to TF (%HF; HF/TF x 100) were used as indices of sympathovagal balance and parasympathetic activities, respectively. 3. In the present study, QTc dispersion failed to correlate with LF/HF and %HF. Systolic blood pressure and pulse rate increased significantly during tooth extraction; however, changes in these variables failed to correlate with QTc dispersion. 4. These results suggest that QTc dispersion is not associated with the power spectrum of R-R variability and that it does not affect the blood pressure response during tooth extraction.