Short-term variability of systolic blood pressure and heart rate in normotensive subjects

Abstract. Short-term fluctuations in systolic blood pressure (SBP) and heart rate (HR) and their inter-relationship were analysed in a group of normotensive middle-aged men (n= 16) using a multivariate autoregressive modelling technique. This study is the first to evaluate the beat-to-beat variability of SBP and HR in a group of real normotensive subjects. Direct intra-arterial blood pressure was registered together with ECG using an ambulatory tape recording technique (the Oxford method). Power spectrum density estimates (PSD) were used as a measure of the variability. PSDs were calculated over 3-min periods for four basic physiological conditions: during sleep and in the supine, sitting and standing positions. The inter-relationship between the blood pressure and heart rate variabilities was analysed using a closed-loop model. In agreement with results presented earlier in the literature, the beat-to-beat variation in SBP and HR was concentrated in three typical power spectrum regions: the high-frequency (HF = 0·15-0·35 Hz) region (respiration), the mid-frequency (MF = 0·075-0·15 Hz) region (vasomotor oscillation) and the low-frequency (LF = 0·02-0·075 Hz) region (thermoregulation). The variability changes considerably between different situations, especially that of the MF region. The variability was most prominent in the MF region and in the standing position. The variability was generally smallest in the HF region and in sleep. The results also demonstrate that the beat-to-beat variability in SBP and HR can considerably affect one another.     

Resistance exercise training improves heart rate variability in women with fibromyalgia

Fibromyalgia (FM) is characterized by generalized muscle pain, low muscle strength and autonomic dysfunction. Heart rate (HR) variability (HRV) is reduced in individuals with FM increasing their risk for cardiovascular morbidity and mortality. We tested the hypothesis that resistance exercise training (RET) improves HRV, baroreflex sensitivity (BRS) and muscle strength in women with FM. Women with FM (n = 10) and healthy controls (n = 9), aged 27-60 years, were compared at baseline. Only women with FM underwent supervised RET 2 days per week for 16 weeks. Baseline and post-training measurements included HRV and spontaneous baroreflex sensitivity (BRS, alpha index) from continuous electrocardiogram and blood pressure (BP) recorded with finger plethysmography during 5 min in the supine position. RR interval, total power, log transformed (Ln) squared root of the standard deviation of RR interval (RMSSD), low-frequency power and BRS were lower (P<0.05), and HR and pulse pressure were higher (P<0.05) in women with FM than in healthy controls. After RET, mean (SEM) total power increased (387 +/- 170 ms(2), P<0.05), RMSSD increased (0.18 +/- 0.08 Ln ms, P<0.05) and Ln of high-frequency power increased (0.54 +/- 0.27 Ln ms(2), P = 0.08) in women with FM. Upper and lower body muscle strength increased by 63% and 49% (P<0.001), and pain perception decreased by 39% in women with FM. There were no changes in BRS, HR and BP after RET. Our study demonstrates that RET improves total power, cardiac parasympathetic tone, pain perception and muscle strength in women with FM who had autonomic dysfunction before the exercise programme.     

Standing shock index: An alternative to orthostatic vital signs

ObjectiveThe lack of a sensitive, practical bedside test for hypovolemia has rekindled interest in the shock index (heart rate divided by systolic blood pressure). Here, we compare the effect of blood donation on standing shock index values with its effect on values for the supine shock index and orthostatic change in shock indicies (OCSI).

Office and laboratory blood pressures as predictors of daily blood pressure level in normotensive subjects and borderline and mild hypertensive subjects

A series of standardized laboratory tests [10 min sitting and supine, 9 min standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)] were performed during intra-arterial blood pressure (BP) recording in 97 healthy unmedicated men, initially classified as normotensive (NT, n = 34), borderline hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office blood pressure (OBP) measurements. After testing, a 24-h intra-arterial ambulatory BP (IABP) recording was obtained while subjects performed their normal activities. Day and night periods were analysed as well as 24-h averages for systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple linear regressions. In normotensive subjects, the supine SBP predicted IABP measurements best (r range 0·39–0·69, P<0·05–0·001). In multiple regression, supine SBP explained 49% of 24-h SBP variance (F = 12·4, P = 0·001). For BHT, supine SBP was also the best predictor (r range 0·09–0·64, P NS to P<0·001), and it explained 37% of 24-h SBP variance (F = 15·6, P = 0·0005). In HT, ERG DBP correlated best with IABP (r range 0·52–0·75, P<0·01–0·001). ERG SBP explained 49% of 24-h SBP (F = 31·0, P = 0·0000) and ERG DBP explained 56% of 24-h DBP (F = 35·4, P = 0·0000) variance. Laboratory BP correlations were generally better with day than with night measurements. OSBP correlated moderately well with IABP in NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but not significantly in BHT. In conclusion, OBP is less closely related to IABP than laboratory BP, but even laboratory BP generally explains less than 50% of IABP variance. Stressors such as exercise are useful only in HT. For BHT, the prediction of IABP with laboratory measures was even weaker than in other groups, and thus ambulatory measurements cannot be replaced by short-duration laboratory measurements and stress tests.     

Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence

BACKGROUND: Elderly pacemaker patients with chronotropic incompetence (CI) may experience orthostatic hypotension (OH) upon standing. The objective of this study was to determine whether a transient increase in heart rate (HR) by overdrive pacing upon standing prevents OH in elderly pacemaker patients. METHODS: We studied the effect of transient overdrive pacing upon standing in mitigating the drop in blood pressure (BP) in 62 pacemaker patients (77 +/- 6 years, 32 F) implanted with DDD pacemaker for sick sinus syndrome (n = 40) or atrioventricular block (n = 22). All patients underwent two standing procedures in random order: a control, with backup (60 bpm) pacing and another with overdrive DDD pacing (at 35 bpm above their baseline rate) for 2 minutes upon standing. Systolic (SBP) and diastolic blood pressure (DBP) and HR were measured while supine (baseline) and 1, 2, and 3 minutes after standing. OH was defined as a drop in SBP > or = 20 mmHg or DBP > or = 10 mmHg during standing. Chronotropic incompetence (CI) was defined as an absence of HR increase of > or = 10 bpm during standing. RESULTS: A total of 17 (27%) patients developed OH upon standing during backup pacing. Baseline clinical characteristics (age, sex, prevalence of diabetes, use of vasoactive medications, and sick sinus syndrome) were similar between patients with or without OH. In patients with or without OH, transient overdrive pacing upon standing increased HR and DBP as compared with baseline (P < 0.05). However, in patients with OH, transient overdrive pacing did not prevent decrease in SBP upon standing and avoided the development of OH in only 10/17 patients (59%). Among those patients with OH, 10/17 (59%) patients had CI. In OH patients with CI, transient overdrive pacing upon standing maintained SBP and DBP as compared to baseline and prevented OH in the majority of patients (80%). By contrast, transient overdrive pacing in OH patients without CI had no significant effect on the decrease in SBP upon standing and prevented OH in only 20% of patients. CONCLUSIONS: OH is common (27%) in the elderly pacemaker population. In a subgroup of these patients, CI may be responsible for the occurrence of OH, and OH can be prevented by transient overdrive pacing upon standing.     

Effect of maternal posture on the umbilical artery flow velocity waveform.

The effect of maternal postural changes on the umbilical artery flow velocity waveform, fetal heart rate and maternal blood pressure was studied in 27 normal singleton pregnancies between 23 and 36 weeks of gestation. A statistically significant change in umbilical artery Pulsatility Index (PI) was established for both maternal standing to supine position (rise) and supine to standing position (drop). These PI changes were not related to gestational age. A statistically significant drop in maternal systolic blood pressure was observed from standing to supine position. The rise in umbilical PI resistance when changing from standing to supine position may be caused by the sluice flow mechanism.     

妊娠期脑出血临床特点及手术疗效分析

目的探讨妊娠期脑出血的临床特点及手术疗效。方法回顾性总结黄冈市妇幼保健院、湖北省中西医结合医院、北京中医药大学东方医院3家医院2012年1月至2018年10月共计接收并手术治疗的49例妊娠期脑出血病例资料。根据妊娠周期分期分为早期组[4例(8.2%)]、中晚期组[6例(12.2%)]、分娩期组[21例(42.9%)]及产褥期组[18例(36.7%)]脑出血,依据治疗脑出血的方式分为开颅组和穿刺组,分析妊娠期脑出血特征及临床疗效。结果49例患者血肿平均体积为(53.37±8.65)mL。开颅术中早期组1例,中晚期组1例,分娩期组9例,产褥期组11例;血肿穿刺术中早期组3例,中晚期组5例,分娩期组12例,产褥期组7例。与妊娠早、中晚期相比较,分娩期及产褥期脑出血不同部位发生率差异有统计学意义(P<0.05);早期组、中晚期组、分娩期组及产褥期组脑出血采取开颅术及穿刺术治疗的比例差异无统计学意义(P>0.05)。开颅组和穿刺组患者术前GOS评分差异无统计学意义(P>0.05),术后GOS评分差异有统计学意义(P<0.01)。开颅组和穿刺组患者术后总有效率差异有统计学意义(P<0.01)。结论妊娠期脑出血可发生在整个妊娠期,尤其是分娩期及产褥期发生率高。穿刺引流术和开颅术均是有效清除妊娠期脑出血血肿的治疗方法,穿刺术的疗效可能优于开颅术。     

The impact of arm position on the measurement of orthostatic blood pressure

Blood pressure is a standard vital sign in patients evaluated in an Emergency Department. The American Heart Association has recommended a preferred position of the arm and cuff when measuring blood pressure. There is no formal recommendation for arm position when measuring orthostatic blood pressure. The objective of this study was to assess the impact of different arm positions on the measurement of postural changes in blood pressure. This was a prospective, unblinded, convenience study involving Emergency Department patients with complaints unrelated to cardiovascular instability. Repeated blood pressure measurements were obtained using an automatic non-invasive device with each subject in a supine and standing position and with the arm parallel and perpendicular to the torso. Orthostatic hypotension was defined as a difference of ≥ 20 mm Hg systolic or ≥ 10 mm Hg diastolic when subtracting standing from supine measurements. There were four comparisons made: group W, arm perpendicular supine and standing; group X, arm parallel supine and standing; group Y, arm parallel supine and perpendicular standing; and group Z, arm perpendicular supine and parallel standing. There were 100 patients enrolled, 55 men, mean age 44 years. Four blood pressure measurements were obtained on each patient. The percentage of patients meeting orthostatic hypotension criteria in each group was: W systolic 6% (95% CI 1%, 11%), diastolic 4% (95% CI 0%, 8%), X systolic 8% (95% CI 3%, 13%), diastolic 9% (95% CI 3%, 13%), Y systolic 19% (95% CI 11%, 27%), diastolic 30% (95% CI 21%, 39%), Z systolic 2% (95% CI 0%, 5%), diastolic 2% (95% CI 0%, 5%). Comparison of Group Y vs. X, Z, and W was statistically significant (p < 0.0001). Arm position has a significant impact on determination of postural changes in blood pressure. The combination of the arm parallel when supine and perpendicular when standing may significantly overestimate the orthostatic change. Arm position should be held constant in supine and standing positions when assessing for orthostatic change in blood pressure.     

Diurnal variability in orthostatic tachycardia: implications for the postural tachycardia syndrome

Patients with POTS (postural tachycardia syndrome) have excessive orthostatic tachycardia (>30 beats/min) when standing from a supine position. HR (heart rate) and BP (blood pressure) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR and BP is not known. In the present study, we tested the hypothesis that there is diurnal variation of orthostatic HR and BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR and BP were obtained in the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning (102±3 beats/min) than in the evening (93±2 beats/min; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 beats/min in the morning compared with 100±3 beats/min in the evening; P=0.012) and controls (89±3 beats/min in the morning compared with 80±2 beats/min in the evening; P=0.005) when analysed separately. There was no diurnal variability in orthostatic BP in POTS. A greater number of subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared with the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.     

子痫前期患者子宫动脉多普勒与血清chemerin的变化及意义

目的:讨论妊娠期高血压孕妇和正常妊娠妇女妊娠早、中、晚期子宫动脉血流变化及血清chemerin变化的规律及意义。方法:选取潍坊市妇幼保健院系统产前检查的孕妇共300例作为研究对象,分别于妊娠14周、24周、34周收集和测量两组孕妇的血液样本和子宫动脉多普勒信息。比较两组孕妇血清chemerin浓度,子宫动脉舒张末期流速(S/D)、搏动指数(PI)、阻力指数(RI)。结果:1)子痫前期患者血清中chemerin浓度明显高于对照组(P<0.05),且重度子痫前期组明显高于轻度子痫前期组(P<0.05)。2)子宫动脉血流动态变化:正常妊娠组孕妇随妊娠进展,子宫动脉RI、PI、S/D 3项指标逐渐降低,妊娠早、中、晚期分别比较,均有统计学差异(P<0.01)。子痫前期组孕妇子宫动脉RI、PI、S/D 3项指标以孕晚期最高,妊娠早、中、晚期分别比较,均有统计学差异(P<0.01)。子痫前期组孕妇妊娠中、晚期子宫动脉3项指标均高于正常妊娠组,有统计学差异(P<0.01)。3)子痫前期患者血清中chemerin浓度在孕早期与子宫动脉血流无明显相关性,在妊娠中晚期呈明显正相关。结论:随着妊娠进展,子痫前期患者血清中chemerin浓度逐渐升高,正常妊娠妇女子宫动脉的血流阻力逐渐下降;而子痫前期组孕妇随妊娠进展子宫动脉的血流阻力明显升高。两者共同参与妊娠期高血压的发病。     

青少年原发性高血压临床特点分析与运动干预

目的从临床角度探讨青少年原发性高血压(EH)发病影响因素,血压与左心室构型、内皮功能的相关性,并分析运动干预的效果。方法32例14～25岁轻中度高血压病患者,20例性别、年龄及体重指数匹配的志愿者作为对照;询问病史、个人史及家族史;监测卧、立位血压变化,给予8周有氧运动干预,干预前后行24h动态血压(ABPM)监测及心脏多普勒超声检查。结果青少年EH以脑力劳动者居多,家族史阳性发生率为94%(30/32),“母体效应”明显,为59%(19/32),高血压组肥胖的发生率高于对照组,出生体重犤(3.0±0.4)kg犦小于对照组犤(3.4±0.3)kg犦;卧立位血压变化明显大于对照组(t=4.9,P<0.05);ET水平高于对照组(t=9.4,P<0.05)。诊所血压与ABP呈正相关,左室重构指数CR与24h平均收缩压(24hSBP),白天平均收缩压(dSBP),夜间平均收缩压(nSBP)及卧立位血压变化(ΔBP)正相关(r=0.5,0.5,0.4);运动干预后诊所血压及24h平均收缩压、白天收缩压明显下降(t=3.5,4.2,P<0.05)。结论青少年EH具有明显的家族聚集性和“母体效应”;家族史阳性、出生体重偏低、肥胖及情绪急躁者为高危人群;体重指数收缩压及交感神经活性增加可能是青少年左室重构影响因素之一;有氧运动是一项适合治疗青少年高血压的有效干预措施。     

星状神经节阻滞治疗自主神经功能紊乱综合征前后的血流动力学变化

目的 :探讨自主神经功能紊乱综合征治疗前后的血流动力学变化。方法 :选择 30例自主神经功能紊乱综合征患者 ,采用星状神经节阻滞 (SGB)复合Naosan疗法和音乐运动疗法 ,并分别测定治疗前后的动脉收缩压 (SBP)、舒张压 (DBP)、脉搏 (HR)、每搏输出量 (SV)、心脏指数 (CI)以及体循环血管阻力 (SVR)。结果 :治疗前后比较平卧位时仅表现为SVR有统计学意义 (P <0 .0 1) ;站立 10min后SBP、SV、CI有显著性升高而SVR有显著性降低 (P <0 .0 5或P <0 .0 1)。结论 :治疗后自主神经功能紊乱综合征患者自觉症状有很大改善 ,血流动力学趋于平稳 ,因此 ,星状神经节阻滞复合Naosan疗法及音乐运动疗法对治疗本症有一定价值。     

Effect of acute atenolol on short-term blood pressure variability and baroreflex sensitivity in rats

Beta-blocker therapy for hypertension or coronary artery disease is common, but there are a lot of controversies about its effects on short-term blood pressure variability and arterial baroreceptor reflexes. The aim of this study was to evaluate the effects of acute atenolol on baroreflex sensitivity (BRS) and on the spontaneous variability of systolic blood pressure (SBP) and RR intervals in conscious rats. Ten Wistar rats equipped with telemetry system were evaluated: 1) under control conditions; 2) after injection of saline; and 3) during beta1-adrenergic blockade by atenolol. Fast Fourier transform analysis was applied to RR intervals and SBP. Atenolol increased RR intervals significantly by 14% and the variation coefficient of the RR intervals by 31%. SBP was reduced significantly by 9%. In frequency domain, beta1-blockade in RR intervals increased very low frequency by 33% and the total power by 22% and decreased low frequency by 25%. The ratio of low to high frequency power decreased by 60%. Frequency domain variables in SBP were not significantly changed after beta1-adrenergic receptor blockade. BRS (gain alpha) was not significantly altered by beta-blockers. Acute atenolol decreased SBP and increased RR intervals with no change in BRS, indicating 'resetting' of baroreflex function.     

Orthostatic hypertension in patients with type 2 diabetes

OBJECTIVE: The prevalence and clinical importance of orthostatic hypertension (OHT) in diabetic patients has not been elucidated, in contrast to orthostatic hypotension, which is occasionally found in diabetic patients with autonomic neuropathy. RESEARCH DESIGN AND METHODS: The prevalence and severity of orthostatic hypertension was investigated in 277 Japanese male patients with type 2 diabetes, including 90 hypertensive patients and 128 nondiabetic age-matched male subjects. Patients treated with antihypertensive drugs were excluded from the study. OHT was defined as an increase in diastolic blood pressure (DBP) from <90 to >or=90 mmHg and/or an increase in systolic blood pressure (SBP) from <140 to >or=140 mmHg after standing from supine position. Clinical profiles and several serum biochemical parameters were determined in addition to chest X-rays and electrocardiograms. RESULTS: The prevalence of OHT in normotensive and hypertensive diabetic patients was significantly higher than in control subjects (12.8 vs. 1.8%, P < 0.01, for normotensive patients; 12.6 vs. 11.1%, not significant, for hypertensive patients). Orthostasis induced a mean increase of 6.8 +/- 11.4 mmHg in SBP and 9.1 +/- 5.2 mmHg in DBP in diabetic patients with OHT compared with those without OHT (-1.0 +/- 9.0 and 3.8 +/- 6.6 mmHg, respectively). Vibration sensation in the lower limb was reduced in diabetic patients with OHT, but the percent coefficient of variation of RR interval, cardio-to-thoracic ratio on chest X-ray, and serum triglyceride levels were higher in these patients compared with normotensive diabetic patients without OHT. CONCLUSIONS: Orthostatic hypertension is a novel complication in normotensive diabetic patients and may associate with early stage neuropathy and development of sustained hypertension.     

Effects on baroreflex sensitivity measurements when different protocols are used to induce regular changes in beat-to-beat intervals and systolic pressure

Baroreflex sensitivity is becoming an important clinical measurement. Nevertheless there is no recommend standard measurement protocol. This study assessed the ability of eight protocols to induce regular changes in cardiac beat-to-beat interval and systolic pressure (SP), and the effect each protocol had on baroreflex sensitivity (BRS). Twelve subjects had changes in cardiac beat-to-beat intervals and SP levels induced at 8 times a minute by following 8 different protocols, each for 3 min. These comprised breathing in a supine and standing posture, breathing through a resistance, breathing into a closed orifice (the breathing protocols), and performing handgrip exercises, being rocked, having legs raised and lowered, and being presented with mental arithmetic questions (the non-breathing protocols). Induction success of each protocol was determined by the percentage of cardiac beat-to-beat interval and SP level signals with a peak at 8 times per minute in their frequency spectra. The consistency of the induced changes was measured by a signal-to-noise ratio (SNR). BRS was calculated from the frequency spectra. The induction success was 85% for breathing and 31% for non-breathing protocols. The consistency of cardiac beat-to-beat interval changes was highest with supine breathing (SNR = 1.6 +/- 0.3) and resistance breathing (SNR = 1.5 +/- 0.5) protocols. The consistency of SP level changes was highest with resistance breathing (SNR = 1.0 +/- 0.3) and breathing into a closed orifice (SNR = 1.0 +/- 0.5) protocols. BRS values in the supine breathing protocol (24 +/- 10 ms mmHg(-1)) and the handgrip protocol (32 +/- 3 ms mmHg(-1)) were significantly greater (p < 0.05) than for standing breathing (11 +/- 5 ms mmHg(-1)), resistance breathing (17 +/- 8 ms mmHg(-1)) or breathing into a closed orifice (12 +/- 5 ms mmHg(-1)) protocols. Different protocols have different induction successes and degrees of effectiveness in inducing cardiac beat-to-beat and SP level changes. BRS is affected by the induction protocol used, highlighting the need for a standard measurement protocol.     

Assessment of the effect of mirodenafil on the hemodynamics of healthy male korean volunteers administered tamsulosin: a randomized, double-blind, placebo-controlled, 2-period crossover study

BackgroundBoth mirodenafil, a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction, and tamsulosin, a selective α_1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia, have mild vasodilational effects.ObjectiveThe aim of this study was to investigate the effect of mirodenafil on the hemodynamics of healthy volunteers who were administered tamsulosin.MethodsHealthy, Korean normotensive male volunteers were enrolled in a randomized, placebo-controlled, double-blind, 2-sequence, 2-period crossover study. Mirodenafil 100 mg or placebo was administered orally after pretreatment with tamsulosin 0.2 mg once daily for 7 days in each period, with a 1-week washout period. Blood pressure (BP) and pulse rate (PR) in supine and standing positions were measured repeatedly before and until 24 hours after the administration of mirodenafil or placebo. The mean differences from the baseline values of the maximum changes of BP and PR, which were measured at 4 and 24 hours, were analyzed by using a mixed-effects model.ResultsEighteen subjects (mean [SD] age, 26.8 [3.9] years; weight, 65.5 [7.0] kg) were administered any trial medication, and 16 of them completed the study. For 4 hours/24 hours after mirodenafil administration, the mean maximal changes from baseline versus placebo in supine systolic BP, diastolic BP, and PR were ?1.0 mm Hg (95% CI, ?4.2 to 2.2) (P = 0.53)/?1.2 mm Hg (95% CI, ?5.3 to 2.9) (P = 0.56), ?2.1 mm Hg (95% CI, ?4.6 to 0.4) (P = 0.10)/?1.1 mm Hg (95% CI, ?3.9 to 1.6) (P = 0.39), and 7.2 beats/min (95% CI, 4.7 to 9.6) (P < 0.05)/4.8 beats/min (95% CI, 1.4 to 8.1) (P < 0.05), respectively. Those changes in a standing position were ?4.0 mm Hg (95% CI, ?8.9 to 0.9) (P = 0.10)/?4.3 mm Hg (95% CI, ?10.0 to 1.5) (P = 0.13), ?1.1 mm Hg (95% CI, ?4.9 to 2.7) (P = 0.54)/?1.9 mm Hg (95% CI, ?5.5 to 1.7) (P = 0.27), and 10.7 beats/min (95% CI, 4.4 to 16.9) (P < 0.05)/6.0 beats/min (95% CI, 0.7 to 11.3) (P < 0.05), respectively. A total of 33 adverse events (AEs) were reported in 9 of 18 subjects. The number of subjects with AEs (P = 0.13) and the number of AEs (P = 0.26) were not significantly different between the 2 groups. The most common AEs were vasodilational symptoms, such as nasal congestion, headache, and flushing.ConclusionsThe coadministration of mirodenafil 100 mg did not induce a significant decrease in BP when associated with an increase in PR in these healthy male Korean volunteers administered tamsulosin 0.2 mg compared with placebo. (Clinical Trial Registry, http://cris.cdc.go.kr/cris/en/: KCT0000117).     

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day‐to‐day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70–84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O₂Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6·7 ± 15·4 mmHg (P<0·05, mean ± SD) and 8·2 ± 6·4 mmHg (P<0·01), respectively, whereas HR increased by 9·5 ± 5·0 bpm (P<0·01) and SV decreased by –8·3 ± 7·4 ml (P<0·01) during standing on the first occasion. [O₂Hb] decreased by –3·9 ± 2·9 μmol l^–1 (P<0·01), while [HHb] increased by 1·8 ± 2·2 μmol l^–1 (P<0·01). Group‐averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group‐averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day‐to‐day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.     

Beat-to-beat oscillations in pulse pressure

We compared 5-min standard deviations (SD) and frequency domain measures of beat-to-beat pulse pressure (PP) variability with those of RR-interval, systolic (SBP) and diastolic (DBP) blood pressure variabilities, and with cross-spectral baroreflex sensitivity (BRS) in a population-based sample of 150 healthy individuals, aged 35-64 years. Beat-to-beat variability of PP was composed of similar frequency components as the other spectral variabilities, and was closely related to SBP variability. The proportion of high frequency (HF) component from overall variability was higher in PP variability than in SBP and DBP variabilities. The low frequency (LF) component and the SD of beat-to-beat PP correlated inversely with BRS (-0.48 and -0.32, respectively; P<0.001 for both). To test a hypothesis that arterial stiffening is associated with increased beat-to-beat oscillation in PP, we examined associations of beat-to-beat PP variability with risk factors of atherosclerosis, i.e. with age, gender, smoking, blood pressure, body mass index, serum lipids, glucose, insulin and homeostasis model assessment of insulin resistance. The SD of beat-to-beat PP variability correlated with age (0.21, P = 0.010), PP (0.31, P<0.001) and body mass index (0.22, P = 0.008). The LF component of PP variability correlated not only with age (0.17, P = 0.041), PP (0.27, P = 0.001) and body mass index (0.22, P = 0.007), but also with serum insulin (0.17, P = 0.042), homeostasis model assessment of insulin resistance (0.18, P = 0.031) and serum triglycerides (0.16, P = 0.048). Our findings suggest that increased beat-to-beat oscillation of PP reflects arterial stiffening and impaired baroreflex function.     

Baroreflex sensitivity in the elderly: influence of age, breathing and spectral methods

Baroreflex sensitivity (BRS) has been proposed as a diagnostic parameter for neurological disorders and as a survival-prognosis parameter in diabetic and cardiac patients. Therefore reference values and the reproducibility of BRS were assessed, taking into account the possible influence of age, gender, test conditions and some analysis variants. Healthy subjects (n=191) were randomly selected from the 50-75-year-old general population (the Hoorn Study). Variations in blood pressure and heart rate were recorded non-invasively during three breathing modes: spontaneous (3 min), slow metronome (1 min; 6 breaths/min=0.1 Hz) and fast metronome (1 min; 15 breaths/min=0.25 Hz), all in a supine position. From these recordings, BRS was assessed as the transfer gain between changes in blood pressure and heart period, and as the alpha coefficient. BRS values ranged from 5.0 to 8.9 ms.mmHg(-1). Slow metronome breathing resulted in higher BRS values than fast breathing, while during spontaneous breathing BRS in the low-frequency band was lower than that in the high-frequency band (respiratory origin). BRS values decreased with lower coherence criteria. BRS-alpha was significantly higher than BRS-gain. While regression analysis showed no gender differences, BRS decreased with age. Therefore age-specific reference values were calculated. The reproducibility of BRS values was in general moderate, with reliability coefficients ranging from 43 to 81% and coefficients of variation ranging from 34 to 59%. In conclusion, this study shows age, breathing mode, frequency and coherence threshold to affect measures of BRS. Therefore these factors should be considered in clinical studies; appropriate reference values are given.     

QT-interval variability and autonomic control in hypertensive subjects with left ventricular hypertrophy

Left ventricular hypertrophy is a risk factor for sudden death. Malignant ventricular arrhythmias originate from altered cardiac repolarization. Ample data have described spatial abnormalities in cardiac repolarization [QT interval (QT) dispersion] in subjects with hypertension; more data are needed on temporal changes. This study was designed to assess the QT variability index (QTVI), the slope between QT and the RR interval (QT-RR(slope)) and spectral QT variability in subjects with arterial hypertension. The results were compared with those from a population at high risk of sudden death, i.e. patients with hypertrophic cardiomyopathy (HCM) who had received an implantable cardioverter/defibrillator (ICD), and those from normotensive control subjects. A total of 44 hypertensive subjects, six patients with HCM and an ICD and 33 control subjects underwent simultaneous short-term recording (256 beats) of QT, RR and systolic blood pressure variability, in the supine position, during controlled breathing. QTVI and spectral components of QT variability in the hypertensive group were significantly higher than in normotensive control subjects (P<0.001), but significantly lower than in patients with HCM and an ICD (P<0.001). The severity of left ventricular hypertrophy correlated significantly with QTVI and the ratio of low-frequency (LF) to high-frequency (HF) power obtained from the RR variability spectra (RR(LF/HF), slope=0.24, P<0.05; QTVI, slope=4.06, P<0.0001; intercept, slope=2.40, P<0.05; chi(2)=38.8; P<0.0001). The QT--RR slope was significantly higher only in patients with HCM and an ICD (P<0.001). In conclusion, the increased QTVI and the correlation of this index with left ventricular hypertrophy indicates that hypertension increases temporal cardiac repolarization abnormalities. At the level of the cardiac sinus node, this alteration is associated with increased sympathetic and reduced vagal modulation. As already noted in patients with HCM, the increased QTVI could be a factor responsible for triggering malignant ventricular arrhythmias in subjects with hypertension.