Effects of Menstrual Cycle on Cardiac Autonomic Innervation As Assessed By Heart Rate Variability

Objective: The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Methods: Forty‐three nonobese regularly cycling women (age 29 ± 6, range 20–38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 ± 1 days and luteal phase 21 ± 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04–0.15 Hz), high frequency peak (HF, 0.15–0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. Results: The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 ± 1.5 vs 1.6 ± 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. Conclusion: We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation. A.N.E. 2002;7(1):60–63     

Biochemical Bone Turnover Markers in Patients with Ankylosing Spondylitis

In this study, bone formation markers [alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP) and osteocalcin (BGP)] and bone resorption markers [pyridinium cross-links: pyridinoline (Pyd) and deoxypyridinoline (Dpyd)] were studied in 44 patients with ankylosing spondylitis (AS) and in a control group of 41 subjects. The AS group was classified according to duration of disease, erythrocyte sedimentation rate (ESR) values and gender. Urinary Pyd and Dpyd concentrations of the patients were higher than in the control group, concomitant with the lower T-score values of the patients in both the anteroposterior lumbar spine and femoral neck. Although a correlation between markers of disease activity [ESR and C-reactive protein (CRP)] and bone turnover markers was not observed, urinary excretion of Dpyd and Pyd was enhanced in the ESR >20 mm/h subgroup compared with the ESR ≤20 mm/h subgroup. A significant elevation of urinary Dpyd was also observed in the female subgroup and long disease duration subgroup. Serum ALP, BALP and BGP levels of the patients and control group were not statistically different (p> 0.05). No significant differences were observed between mineral and calcitropic hormone levels in either group, and total testosterone levels of the patients were within the reference range. According to this study, urinary Pyd levels are elevated in patients with AS. Gender, duration of disease and ESR also have an impact on urinary excretion of these collagen compounds. It can be concluded that bone turnover in patients with AS reflects normal osteoblastic activity and high osteoclastic activity. Received: 12 March 1999 / Accepted: 25 August 1999     

正常人群的心率变异性分析

将１００４例正常人分三个年龄组进行短程（５ｍｉｎ）心率变异性（ＨＲＶ）分析。时域法的参数为平均心率标准差（ＨＲＳＤ），连续５ｍｉｎ节段平均正常ＲＲ间期标准差（ＳＤＡＮＮ），相邻ＲＲ间期差的均方根（ｒＭＳＳＤ），相邻ＲＲ间期差异≥５０ｍｓ的百分数（ＰＮＮ_（５０））；频域法的参数为极低频（ＶＬＦ）、低频（ＬＦ）、高频（ＨＦ）成分，总功率（ＴＰ）及ＬＦ／ＨＦ比值。各指标间做相关分析。结果：４５岁以上组ＨＲＳＤ、ＳＤＡＮＮ、ｒＭＳＳＤ、ＰＮＮ_（５０）、ＶＬＦ、ＬＦ、ＨＦ、ＴＰ均低于４５岁以下两组（Ｐ＜０．０５或＜０．０１）。ＳＤＡＮＮ、ｒＭＳＳＤ、ＰＮＮ_（５０）与ＨＦ呈高度正相关（ｒ＞０．７０，Ｐ＜０．０００１），其中以ＳＤＡＮＮ、ＰＮＮ_（５０）相关更好（ｒ＞０．７５，Ｐ＜０．００１），ＳＤＡＮＮ、ｒＭＳＳＤ、ＰＮＮ_（５０）间高度相关（ｒ＞０．８０，Ｐ＜０．０００１）。不同性别ＨＲＶ各参数相比无显著差异。提示：ＨＲＶ随年龄的增长而下降，以迷走神经张力下降为主；各指标中以ＳＤＡＮＮ、ｒＭＳＳＤ、ＰＮＮ_（５０）、ＨＦ能更好地反映迷走神经张力变化。     

Coexistence of Hereditary Multiple Exostoses and Ankylosing Spondylitis

We report a 50-year-old male patient with hereditary multiple exostoses (HME) and ankylosing spondylitis (AS). This is the first case reporting the coexistence of HME and AS. Our patient has multiple exostoses around the knee, elbow and wrist joints. At the age of 40 years, pain in the lower back associated with morning stiffness lasting about an hour and improving with exercise began. His son also has hereditary multiple exostoses but has no sign of AS. HME is an autosomal dominant disorder. AS has a remarkably strong association with the histocompatibility antigen HLA-B27. Owing to the different genetic mechanisms, it is not possible to differentiate between coincidence and association. Coexistence of HME and AS in our patient probably represents a coincidence rather than a real association. Received: 4 September 1998 / Accepted: 4 April 1999     

Efficacy of Methotrexate in the Treatment of Ankylosing Spondylitis: A Three-Year Open Study

The aim of the study was to evaluate the efficacy of methotrexate treatment in patients with ankylosing spondylitis in a 3-year open trial. Seventeen patients, 14 men and three women (mean age 32.7 ± 8.9 years), suffering from ankylosing spondylitis and non-responders to treatment with sulphasalazine, were enrolled in our study. Sixteen of them were evaluable at the end of the study. Methotrexate (7.5–10 mg/week) was administered for 3 years. Efficacy was evaluated on the basis of clinical and laboratory variables, radiographic signs of disease progression and daily dosage of indomethacin. We obtained a good and relatively prompt clinical response except for peripheral arthritis and iridocyclitis; in fact, after 3 months of methotrexate treatment a significant amelioration of the following parameters was observed: visual analogue scale for the evaluation of both night pain and general well-being, Shober’s test, occiput-wall distance, fingertip to floor, erythrocyte sedimentation rate, C-reactive protein level and daily dose of indomethacin. A further improvement was obtained during the subsequent period. Radiographs of the spine and sacroiliac joints did not show any signs of disease progression. Side-effects were a transitory elevation of transaminases (four cases) and slight hypogammaglobulinaemia (one case). Methotrexate treatment may be useful in ankylosing spondylitis, but a combined treatment might be indicated for patients with peripheral arthritis. Received: 26 January 1999 / Accepted: 25 August 1999     

心率变异时域分析对糖尿病患者自主神经功能的评价

采用２４小时动态心电图对８２例糖尿病患者进行心率变异（ＨＲＶ）和心率（ＨＲ）检测。８２例分为五组：Ａ组（无血管合并症）３０例、Ｂ组（合并大血管病变）１１例、Ｃ组（合并小血管病变）１２例、Ｄ组（同时合并大、小血管病变）１９例和Ｅ组（心肾功能不全）１０例，并设正常对照组。结果：糖尿病各组ＨＲＶ显著降低，Ａ组仅２４ｈ内全部正常ＲＲ间期标准差（ＳＤＮＮ，１０４．２０±２９．１９ｍｓ）和２４ｈ内５ｍｉｎ节段平均正常ＲＲ间期的标准差（ＳＤＡＮＮｉｎｄｅｘ，９３．７３±２７．５８ｍｓ）降低（对照组分别为１２７．５２±３８．５７ｍｓ和１１６．１９±３５．７０ｍｓ），Ｐ均＜０．０１；ＨＲ异常主要表现为夜间平均ＨＲ增快，白昼平均ＨＲ仅Ｅ组（８６．７６±１１．３６ｂｐｍ）高于对照组（７６．３８±９．４０ｂｐｍ），Ｐ＜０．０１。表明糖尿病患者存在自主神经受累，白昼心率增快可能是病情严重的征兆。     

The Correlation Dimension of Heart Rate Variability Reflects Cardiac Autonomic Activity

Background: Linear methods of time series analysis such as summary statistics and frequency-domain parameters have been used to measure heart rate variability (HRV). More recently, nonlinear methods including the correlation dimension (CDim) have been used to evaluate HRV. The aim of this study was to examine the effect of autonomic perturbations on the CDim. Methods: The CDim was calculated from 2000 data points (RR intervals) collected over a relatively short period of time (20–40 min) in 12 healthy subjects aged between 20 and 40 years (mean 30 ± 2 years) during: (a) supine rest; (b) head up tilt (sympathetic activation, parasympathetic nervous system activity withdrawal); (c) intravenous infusion of atropine (parasympathetic nervous system activity withdrawal); and (d) following overnight administration of low dose transdermal scopolamine (parasympathetic nervous system augmentation. Results: The CDim was determined at rest (7.8 ± 0.3) and found to be significantly reduced during tilt (5.9 ± 0.4, P < 0.01) and atropine administration (4.2 ± 0.4, P < 0.01) and possibly increased by scopolamine (8.3 ± 0.5, NS). Conclusions: The changes following these interventions suggest that CDim can accurately measure cardiac autonomic nervous system activity.     

Assessment of Thoracolumbar Rotation in Ankylosing Spondylitis: A Simple Tape Method

Results of a ‘new’ method for thoracolumbar rotation by tape (TRPav), simple instrumental rotation (TRi), the modified Schober test and thoracolumbar flexion (ThFL) were correlalated with radiological changes in patients with ankylosing spondylitis (AS). TRPav showed a significant radiological correlation (Ls-r: 0.38; Th-r: 0.31), while the instrument method (TRi) did not; both the Schober test and ThFL, again, correlated fairly highly (Ls-r: 0.71, 0.62; Th-r: 0.49, 0.42). Both inter- and intratester reliability of the tests was good (Bland and Altman plots). Thoracolumbar rotation is one of the three principal levels of spinal motion and seems to be less affected by age. TRPav proved a valid and reliable method for measuring thoracolumbar rotation and clinically is a non-invasive, quick and easy complement to AS measurement methodologies. Received: 20 April 1998 / Accepted: 5 October 1998     

肠易激综合征患者心血管自主神经功能变化与心率变异性的关系

目的 :探讨肠易激综合征 (1BS)患者心血管自主神经功能变化与心率变异性 (HRV)的关系。方法 :对IBS患者 50例进行标准心血管自主神经功能测试 ,将其结果分成阳性组 (DNA+ )及阴性组 (DNA- ) ,健康人 30名为对照组。 2 4h动态心电图进行HRV分析。结果 :IBS患者自主神经功能异常的发生率为 58% ,主要表现为迷走神经功能异常 ;HRV时域分析中DNA+ 组SDNN、SDANN、SDNNindex明显减少 ;DNA+ 及DNA- 组中反映副交感神经张力的RMSSD、PNN50 、HF等指标明显增高 ,LF/HF比值明显减低 ,与对照组比较有显著性差异 (P <0 .0 5)。结论 :IBS患者存在副交感神经张力增加。HRV分析是发现IBS患者自主神经功能异常的较好方法     

Influence of Disease Activity and Chronicity on Ankylosing Spondylitis Bone Mass Loss

We investigated 30 consecutive Brazilian patients with definite ankylosing spondylitis (AS) fulfilling the New York and the European spondyloarthropathy study group classification criteria. The mean age at study was 37 years old and the mean disease duration was 17 years. Bone densitometry employed the dual-energy X-ray absorptiometry (DEXA) technique, using a Hologic QDR-1000/W densitometer. Axial bone mineral density (BMD) was measured in the lumbar spine (L1–L4) and appendicular BMD was measured in the total proximal femur and sub-regions (neck, greater trochanter, intertrochanter and Ward’s triangle). Based on World Health Organisation criteria, the lumbar spine showed osteopenia or osteoporosis in 50% of the patients, while 86% had osteopenia or osteoporosis in the total proximal femur. When compared with the normal population, the patients showed a significant BMD decrease in the lumbar spine and total proximal femur with sub-regions, except for the femoral neck. A comparison of BMD between patients with active and inactive disease did not reveal a significant effect of clinical disease activity on the lumbar spine and total proximal femur with sub-regions, except for Ward’s triangle. Concerning disease chronicity, there were significant positive correlations between disease duration and lumbar spine, total proximal femur, greater trochanter and intertrochanteric regional BMD. This false increase in lumbar spine BMD found mostly in patients with long standing AS was due to the presence of paravertebral calcification and ossification. We conclude that the bone mass loss in AS is better evaluated in the proximal femur, because of the greater sensitivity of bone densitometry in this region, which is almost free of artefacts. Received: 1 September 1998 / Accepted: 24 February 1999     

正常孕妇24小时的心率变异分析

为观察正常孕妇的HRV以及室性心律失常的发生率 ,探讨孕妇心脏自主神经功能的平衡情况 ,对 6 9例孕妇(按妊娠周期分成 3组 )和 30例正常未孕妇女进行 2 4h动态心电图检查 ,监测 2 4h的室性心律失常 (PVC) ,对其时域、频域结果进行分析。结果显示 :与对照组相比 ,怀孕各组大部分时域、频域指标均明显降低 (P <0 .0 5 ) ,但与妊娠周期无关 ;而怀孕伴PVC与怀孕无PVCHRV比较有显著性差异 (P <0 .0 5 )。提示怀孕伴PVC可能与心脏自主神经功能失衡有关。HRV分析对临床评价孕妇心脏自主神经功能有一定的参考意义。     

Heart Rate Variability Assessment of the Effect of Physical Training on Autonomic Cardiac Control

Background: The effect of exercise interventions on autonomic nervous system (ANS) control of the heart by heart rate variability (HRV) is often investigated in just one position. It was hypothesized that results of exercise‐induced changes on ANS are dependent on body position and that it is possible to distinguish between exercise induced changes in vagal and sympathetic influence by taking measurements in different body positions. Methods: One hundred eighty‐three (male = 100, female = 83) healthy volunteers, between 18 and 22 years, participated in a prospective twelve week medium to high intensity exercise intervention study with a self‐control design. The influence of the exercise intervention was investigated on supine, rising, and standing as well as on the orthostatic response. Time domain, frequency domain and nonlinear (Poincaré) HRV analysis were performed. Results: The exercise intervention lead to a significant increase (P < 0.05) in vagal influence during supine, rising, and standing. Sympathetic control in the supine position was decreased and increased during rising and standing. In the initial orthostatic response to rising from the supine position, the exercise intervention lead to increased (P < 0.05) vagal withdrawal as well as increased sympathetic control. The orthostatic response measured as the difference between standing and supine indicated only an exercise induced increase in sympathetic control. Conclusions: Exercise‐induced changes in sympathetic and parasympathetic ANS control differ, depending on posture and period of measurement. Exercise induced changes in parasympathetic and sympathetic outflow, respectively, can be extracted from measurements from supine, through the orthostatic response, to standing, thereby detecting changes in ANS that are otherwise obscured.     

自主神经系统在阵发性心房颤动发作前后心率变异性变化中的作用

目的分析阵发性心房颤动发作前后心率变异性的变化,探讨自主神经系统在阵发性心房颤动中的作用。方法采用动态心电图记录28例阵发性心房颤动患者24h心电信息,分析其发作前后5min及白天（6：00～22：00）和夜间（22：00～6：00）的心率变异性指标。结果心房颤动发作前5min平均正常R—R间期的标准差（SDNN）、高频成份（HF）较终止后5min显著升高（P〈0．01）,低频／高频比值（LF／HF）显著降低（P〈0．01）,LF无变化：LF、HF白天均高于夜间（P〈0．01）,白天与夜间SDNN、LF／HF无差异;阵发性心房颤动发作前5minSDNN与阵发性心房颤动发作频率呈正相关（r=0．545。P〈0．01）,LF／HF与阵发性心房颤动发作频率和持续时间呈负相关（r=-0532、-0．563,均P〈0．01）。结论阵发性心房颤动发作前心率变异性升高,迷走神经支配占优势,使心房颤动得以诱发和持续。     

心率变异性与急性脑血管病关系的分析

采用心率变异性(HRV)时域指标研究急性脑血管病患者HRV改变及其与病变类型、部位、范围大小的关系.结果显示,急性脑血管病组SDNN(82.18±28.94ms)和HRVI(21.01±4.06)较正常对照组(125.87±31.10ms,25.80±4.26)显著降低,P<0.01;脑出血组与脑梗塞组分别与脑动脉硬化组比较呈显著差异;HRV值丘脑区<基底节区<颞、额、顶叶区<小脑区;多发性脑梗塞SDNN与HRVI显著低于腔隙性脑梗塞(P<0.01),提示脑血管病急性发作期交感神经活动增强,而迷走神经活动受抑制,其改变程度与病变类型、部位及范围大小有关,与自主神经功能紊乱密切相关.因此,HRV分析也是预测急性脑血管病发生猝死危险性的最有价值的指标之一.     

冠心病心肌缺血发作时自主神经功能的变化

采用心率变异性（ＨＲＶ）自回归（ＡＲ）和快速傅立叶转换（ＦＦＴ）两种频域法对比分析５０例冠心病病人和５０例正常人ＨＲＶ的昼夜变化及心肌缺血时与无缺血时的ＨＲＶ变化，并对两种频域法进行相关性分析。结果表明：冠心病组和对照组的ＨＲＶ呈昼夜变化，白天以低频成分（ＬＦ，代表交感神经活性）占优势，夜间以高频成分（ＨＦ，反映迷走神经活性）占优势；冠心病心肌缺血病人的ＨＲＶ昼夜变化减少（ＡＲ法，ＬＦ／ＨＦ：冠心病组为２．２±０．９ＶＳ０．８±１．１，对照组为２．４±１．２ＶＳ０．３±０．８，Ｐ＜０．０５），清晨自主神经调节发生突然变化，即由迷走神经兴奋转为交感神经兴奋；劳累型心绞痛病人心肌缺血时ＬＦ增高（１６３±１３２ｍｓ２ＶＳ２４７±１６２ｍｓ２，Ｐ＜０．０５），ＨＦ减少（７５±２１ｍｓ２ＶＳ５７±１１ｍｓ２，Ｐ＜０．０５），心肌缺血次数与ＬＦ呈正相关（ｒ＝０．６７）．上午６～１０时心肌缺血发生最多。两种能谱估计法呈高度正相关（ｒ＝０．９８）。提示：劳累型心绞痛的发作与交感神经功能亢进、迷走神经张力减弱有关；清晨自主神经功能调节的突然变化可起板机作用，使此时心肌缺血的发生频度增高。     

Impaired Autonomic Nervous System in Alcoholics Assessed by Heart Rate Variation

The suppression of heart rate variation reflects cardiac autonomic nervous dysfunction and is known to be associated with a poor prognosis or sudden death in diabetic patients. We investigated consecutive changes in the heart rate variation in 51 alcoholics using the coefficient of variation of R-R interval (CV_RR). To correct for age effects, a ratio of CV_RR to the standard predicted value (CV_P) was calculated. On the whole, CV_RR/CV_P was suppressed on admission and on the 7th day of abstinence and increased on the 30th day. However, alcoholics could be divided into two groups by their CV_RR/CV_P on the 30th day: one group with transient autonomic dysfunction whose CV_RR/CV_P was more than 0.8 (n= 32), and the other group with persistent autonomic dysfunction whose CV_RR/CV_P was less than 0.8 (n= 19). Withdrawal hypertension occurred more frequently (63% vs. 19%) and mean systolic pressure (159 ± 24 mmHg vs. 138 ± 17 mmHg) was higher in the latter group than in the former, suggesting that persistent autonomic damage might, at least in part, contribute to withdrawal hypertension. To investigate further the relationship between the persistent autonomic damage and other complications, the CV_RR/CV_P on the 30th day of abstinence was analyzed in an additional 85 alcoholics (total n= 136). Persistent suppression of the CV_RR/CV_P was more frequently found in alcoholics with leg paresthesia (64%, n= 22), the Wernicke-Korsakoff syndrome (73%, n= 11), or diabetes mellitus (69%, n= 68), than in alcoholics without these complications (31%, n= 35). This suggests that persistent autonomic dysfunction reflects damage in both the peripheral and the central autonomic nervous systems and is exacerbated by the complication of diabetes mellitus. The measurement of CV_RR on the 30th day of abstinence is useful to evaluate persistent autonomic dysfunction in alcoholics.     

Autonomic Function in Patients with Functional Dyspepsia Assessed by 24-Hour Heart Rate Variability

The function of the autonomic nervous system was assessed in 23 patients with dysmotility-like functional dyspepsia and 12 healthy volunteers by analysis of 24-hr heart rate variability and a battery of five standardized sympathetic and parasympathetic cardiovascular reflex tests. Measures of heart rate variability were obtained by analysis of ambulatory electrocardiographic recordings using both the time and the frequency domain methods. The values of parameters reflecting vagal activity (HF, rMSSD) were significantly lower in patients with functional dyspepsia. Individual analysis of heart rate variability data identified at least one abnormal parameter of vagal function in seven (30.4%) patients, and in five of these the results of parasympathetic cardiovascular reflex tests were also abnormal. Our results suggest impaired efferent vagal function in a subgroup of patients with functional dyspepsia. This abnormality may play a role in the pathogenesis of the disease in these patients.     

Physiological Background Underlying Short-Term Heart Rate Variability

A large number of papers has been published on heart rate variability (HRV) based on the assumption that the specific components of HRV provide specific information about cardiac parasympathetic or sympathetic efferent nerve activity. However, neural control of the cardiorespiratory system is very complex, and the physiological phenomenon underlying HRV in different conditions are far from being fully understood. This review summarizes, in the light of current literature, a series of studies focused on the mechanisms by which fluctuations in neural outflows are transferred into HRV. In the interpretation of HRV analyses, it should be taken into account that: (1) HRV seems to be strongly influenced by the parasympathetic nervous system at all the frequency components; (2) due to sympathovagal interactions, sympathetic outflow is able to reduce the variations generated by vagal modulation also in the high frequency band; and (3) the variations in heart rate reflect fluctuations in the neural activity rather than the mean level of sympathetic or parasympathetic neural activity. Thus, we should be cautious in interpreting a specific component of HRV as a specific marker of sympathetic or parasympathetic cardiac control. Furthermore, due to the complexity of the cardiorespiratory control system, the analysis of short-term HRV should be performed in well-controlled conditions, in which the behavior of the autonomic nervous system is well documented.     

代谢综合征患者血压变异性和心率变异性的临床研究

目的 通过观察代谢综合征(MS)患者血压变异性(BPV)和心率变异性(HRV),探讨MS对心血管系统自主神经功能的影响.方法 入选MS患者(MS组)110例及对照组46例,分别进行24h动态血压和动态心电图监测,对比分析两组的BPV和HRV的指标.结果 (1)MS组的一般资料(性别比、年龄)及HDL-C与对照组比较,差异均无统计学意义(P＞0.05);MS组的体质指数(BMI)、腰围(WC)、腰臀比(WHR)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、体脂含量(FATc)及体脂比例(FATp)与对照组比较,差异均有统计学意义(P＜0.05).(2)MS组BPV中9项指标均较对照组显著性增高(P＜0.05);其余3项(dDBPSD、nSBPSD及nDBPSD)指标升高,但无统计学意义(P＞0.05).(3)MS组HRV各项指标与对照组比较,差异均有统计学意义(P＜0.05).(4)MS与性别、吸烟、心血管病早发家族史、高血压、糖尿病、TG、FBG及MBI具有相关性(P＜0.05);与饮酒、TC、HDL-C及LDL-C无相关性(P＞0.05).结论 MS患者存在心血管系统自主神经功能紊乱,表现为BPV的显著升高和HRV的显著降低,其与性别、吸烟、心血管病早发家族史、高血压病、糖尿病、TG、FBG及MBI相关.