Cardiovascular differences between sham and active iTBS related to treatment response in MDD

BackgroundHeart rate in MDD is often dysregulated, expressed in overall higher heart rates (HR) and lower heart rate variability (HRV). Interestingly, HR decelerations have been reported after stimulation of the DLPFC using rTMS, suggesting connectivity between the DLPFC and the heart. Recently, a new form of rTMS called theta burst stimulation (TBS) has been developed. One form of TBS, intermittent TBS (iTBS), delivers 600 pulses in just 3 min.ObjectiveTo determine whether iTBS aimed at the DLPFC also affects HR, blood pressure and HRV, and whether these cardiac responses at baseline are associated with treatment response.MethodsECG and blood pressure were recorded during both sham and active iTBS in 15 MDD patients, over 30 sessions.ResultsWe found a significantly larger HR deceleration for active iTBS, compared to sham, within the first minute of stimulation. Also, a trend towards an association between HR deceleration and treatment response was found, explaining 26% of the variance. Furthermore, several measures of heart rate variability were significantly higher during iTBS stimulation over sessions, compared to sham. Both systolic and diastolic blood pressure, were lower during active iTBS.ConclusionActive iTBS applied to the DLPFC is able to transsynaptically modulate the autonomic nervous system, in particular the parasympathetic branch, similar to what has been found for conventional rTMS methods. Furthermore, data suggest that the larger the autonomic changes induced at baseline, the better the clinical response after 30 sessions of iTBS.     

Attentional and physiological characteristics of patients with dental anxiety

Twenty patients with dental anxiety were investigated while seated in a dental chair in a dental clinic. Heart rate (HR), heart rate variability (HRV), and skin conductance level (SCL) were recorded while the patients were exposed to scenes of dental treatment as well as a Stroop attentional task. Results showed an attentional bias with longer manual reaction times (RT's) to the incongruent compared to the congruent color words as well as the threat compared to the neutral words. Longer RT's to the incongruent and the threat words were found in the low HRV patients compared to the high HRV patients. Furthermore, all patients showed an increase in HR during exposure and the Stroop task compared to baseline. The HRV showed a decrease during the exposure and the Stroop task compared to baseline. HR and HRV did not differ between exposure and the Stroop task. Moreover, HR and HRV did not return to baseline levels during the recovery period. The SCL showed an increase from baseline to exposure, from exposure to the Stroop task and a decrease in the recovery phase. Results showed the importance of vagal cardiac control in attentional, emotional, and physiological processes in patients suffering from dental fear.     

Hypnotizability-dependent modulation of the changes in heart rate control induced by upright stance

Subjects with high (Highs) and low (Lows) susceptibility to hypnosis show differences in the sensory-motor integration for postural control and in the cardiovascular response to stress and experimental pain. Aim of the experiment was to assess whether the cardiac response to gravity-related stimulation depending on changes in the body position were different in the two groups. Thus, heart rate (HR) and heart rate variability (HRV) were evaluated in sitting and upright position in Highs and Lows. Position-related HRV changes were studied in the time (statistical indexes, Poincaré Plot) and frequency (spectral analysis) domain. Results indicated that upright stance was associated with similar changes in heart rate and different modulation of HRV in the two groups. The association of time and frequency domain analyses allowed hypothesizing different control mechanisms as responsible for the cardiac response to upright stance in Highs and Lows, likely due to a different role of the Very Low Frequency (VLF) spectral component of HRV in the two groups. The results are in line with previous findings indicating a natural protection of Highs against cardiovascular events and suggest that the Highs' cardiac function might be less impaired by microgravity than the Lows' one.     

Peri-ictal heart rate variability parameters as surrogate markers of seizure severity

This study aims at defining objective parameters reflecting the severity of peri-ictal autonomic changes and their relation to post-ictal generalized electroencephalography (EEG) suppression (PGES), with the view that such changes could be detected by wearable seizure detection systems and prove useful to assess the risk of sudden unexpected death in epilepsy (SUDEP). To this purpose, we assessed peri-ictal changes in heart rate variability (HRV) and correlated them with seizure duration, intensity of electromyography-based ictal muscle activity, and presence and duration of post-ictal generalized EEG suppression (PGES). We evaluated 75 motor seizures from 40 patients, including 61 generalized tonic-clonic seizures (GTCS) and 14 other major motor seizure types. For all major motor seizures, HRV measurements demonstrated a significantly decreased parasympathetic activity and increased sympathetic activity in the post-ictal period. The post-ictal increased sympathetic activity was significantly higher for GTCS as compared with non-GTCS. The degree of peri-ictal decreased parasympathetic activity and increased sympathetic activity was associated with longer PGES (>20 s), longer seizure duration, and greater intensity of ictal muscle activity. Mean post-ictal heart rate (HR) was an independent predictor of PGES duration, seizure duration, and intensity of ictal muscle contraction. Our results indicate that peri-ictal changes in HRV are potential biomarkers of major motor seizure severity.     

Sex differences in heart rate variability during sleep following prenatal nicotine exposure in rat pups

The influence of both prenatal nicotine exposure (PNE; 6 mg/kg/day) and sex on heart rate (HR) regulation during sleep versus wakefulness was evaluated in 13, 16 and 26 day old rat pups. Pups were chronically instrumented at least 24 h before testing. On postnatal day 13 (P13), PNE males spent significantly more time in NREM sleep and demonstrated a greater drop in HR when transitioning from quiet wake to sleep compared to age and sex matched controls (-14±5 bpm versus -1±3 bpm, respectively). Heart rate variability (HRV) analysis indicated that this state-dependent drop in HR was primarily associated with a greater reduction in sympathovagal balance (LF/HF ratio) in PNE males compared to controls. No parallel changes in indices of parasympathetic drive (HF power) were identified. In contrast, no significant effect of PNE on HR during sleep versus wakefulness was identified in P13 females. However, independent of state, a significant decrease in HF power was identified in P13 PNE females compared to controls. At P16, state-dependent differences in HR or HRV between PNE and sex-matched control pups were resolved. Additionally, at P26 no significant effect of PNE on state-dependent changes in HR or HRV was identified in either sex. Analysis of the hypothalamic peptide orexin identified that PNE induced approximately a 50% reduction in hypothalamic prepro-orexin mRNA and total mRNA was lowest in PNE males. These findings suggest that PNE induces sex dependent changes in sleep related autonomic regulation of HR during early postnatal development and these changes may be related to epigenetic alterations in the orexin system.     

高血压合并急性脑血管病的心率变异分析

目的：探讨急性脑组织损害对原发性高血压（EH）患者心率变异（HRV）的影响。方法：对26例EH并急性脑血管病（ACVD）患者进行24h动态心电图HRV测定,并与20例EH元ACVD患者进行对比。结果:EH并ACVD组最小心率及平均心率明显高于无ACVD组（P＜0．01;P＜0．01）;24h相邻R-R间期之差的均方根（rMSSD)、相邻R-R间期之差大于50ms的心搏数占心搏总数的百分比（PNN50）较无ACVD组明显减低（P＜0．01;P＜0．001）。结论：EH合并ACVD患者HRV低于EH无ACVD患者,与其自主神经中枢损害有关。     

Autonomic and emotion regulation in bereavement and depression

OBJECTIVES: Prior research suggests important differences between depression and the depressed feelings experienced in the context of bereavement, despite some overlap. Differences include an increase in restlessness, suggesting underlying physiological differences between the groups. METHOD: This study examined the level of depressive symptoms, heart rate (HR), and heart rate variability (HRV), and coping style of 10 bereaved, 10 depressed, and 10 control participants. RESULTS: Bereaved participants showed significantly higher HR than either depressed or control participants, while there were no such differences in HRV. Level of depression in the bereaved group correlated negatively with HRV. Additional analyses showed that the use of passive coping had a marginally significant negative correlation with HRV in bereaved subjects. CONCLUSION: The present data suggest that differences in HR and HRV could be associated with increased cardiovascular fatalities in bereaved individuals, known as the "broken heart phenomenon." These physiological differences have potential implications for both the mental and physical health of the bereaved.     

The deceleration capacity – a new measure of heart rate variability evaluated in patients with schizophrenia and antipsychotic treatment

BackgroundSchizophrenia is associated with increased cardiac mortality. A disturbed autonomic modulation of heart rate (HR) has been described in patients with schizophrenia in whom antipsychotic medication may represent an additional cardiac risk. The novel measure deceleration capacity (DC) of heart rate predicts cardiac mortality in patients with cardiovascular illnesses. The aim of the present paper was to calculate DC in patients with schizophrenia and to compare this measure with established parameters of heart rate variability (HRV).MethodsHRV and DC were calculated in 24-hour electrocardiogram (ECG) recordings of 20 unmedicated, 40 medicated patients with schizophrenia and 40 controls. As activity has a major influence on HRV, 4-hour periods of “sleep-” and “wake-” ECG were evaluated as additional parameters. Actigraphy was used to ensure comparable levels of activity in patients and controls.ResultsThe DC as well as the other established HRV measures were not significantly different comparing unmedicated patients with schizophrenia to healthy controls. However, medicated patients showed a significant reduction of DC calculated from ECG recordings during 4 hour over night periods.ConclusionCalculation of DC might contribute to a better monitoring and identification of an increased risk of cardiac mortality in patients with schizophrenia undergoing antipsychotic treatment.     

Induction of bradycardia in trout by centrally administered corticotropin-releasing-hormone (CRH)

The cardiovascular effects of centrally and peripherally administered synthetic salmon corticotropin-releasing-hormone (CRH), a member of a family of stress-related neuropeptides, were investigated in the unanesthetized trout, Oncorhynchus mykiss. In group 1, trout bearing a cannula in the dorsal aorta, neither intracerebroventricular (i.c.v.) nor intra-arterial (i.a.) injections of CRH produced any significant change in mean heart rate (HR) and mean dorsal aortic blood pressure. These results stand in contrast to the previously reported hypertensive effects of i.a. and i.c.v. injections of trout urotensin-I. In group 2, non-cannulated trout bearing two subcutaneous electrocardiographic electrodes, conditions that are considered to be less stressful to the animals, the baseline level of HR was significantly reduced compared to the corresponding value for cannulated trout. In these trout, no significant change occurred in the HR after i.c.v. administration of 1 pmol of CRH. However, i.c.v. injection of 5 pmol of CRH caused a 12% (P<0.01) decrease in HR during the 20-25 min post-injection period. In addition, the heart rate variability (HRV), a marker of vagal input to the heart, was increased by 120%. The CRH antagonist, CRH-(9-41)-peptide alone had no effect on HR or HRV but blocked CRH-induced bradycardia. In the non-cannulated trout, i.c.v. injection of trout urotensin-I (5 pmol) produced no significant change in HR and HRV. In contrast, i.c.v. administration of angiotensin II (5 pmol) elicited a highly significant 33% (P<0.001) increase in the mean HR as well as inducing a marked (64%) reduction in HRV. Our results suggest that picomolar doses of CRH act centrally to evoke a bradycardia by a probable mechanism that involves enhancement of the parasympathetic drive to the heart.     

Heart rate, tonic cardiac variability and evaluation

Heart rate (HR) and various measures of heart rate variability (HRV) were measured while 29 male and 15 female student volunteers individually rated slide stimuli presented in one-minute intervals. Ratings were factor analyzed and factor scores analyzed as variables. Factor one: “evaluation” accounted for 52.5% of the variances. HR and HRV were not significantly related to the experimental conditions although factor one was related. HR was correlated to measures of HRV [such as the coefficient of variability (CV), coefficient of temporal variability (CVT), a cosine function (FREQ) and to a lesser degree the auto-correlation (RA)]. HR also correlated linearly to evaluation. CVT, CV and RA were also linearly correlated to evaluation. HRV (BURST) was independent of HR, other forms of HRV, and curvilinearly related to evaluation. A cyclic HRV function (FREQ) was found with a mode of 18.7 sec and accounted for 21.4% of the variance of the heart beat data. This cyclic function, not reported previously, should be further investigated.     

Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients

The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug-resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly ( P  < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT.     

Sleep variability and cardiac autonomic modulation in adolescents – Penn State Child Cohort (PSCC) study

ObjectiveTo investigate the effects of objectively measured habitual sleep patterns on cardiac autonomic modulation (CAM) in a population-based sample of adolescents.MethodsWe used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. CAM was assessed by heart rate (HR) variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-h electrocardiogram, on a 30-min basis. The HRV indices included frequency domain (HF, LF, and LF/HF ratio), and time domain (SDNN, RMSSD, and heart rate or HR) variables. Actigraphy was used for seven consecutive nights to estimate nightly sleep duration and time in bed. The seven-night mean (SD) of sleep duration and sleep efficiency were used to represent sleep duration, duration variability, sleep efficiency, and efficiency variability, respectively. HF and LF were log-transformed for statistical analysis. Linear mixed-effect models were used to analyze the association between sleep patterns and CAM.ResultsAfter adjusting for major confounders, increased sleep duration variability and efficiency variability were significantly associated with lower HRV and higher HR during the 39-h, as well as separated by daytime and nighttime. For instance, a 1-h increase in sleep duration variability is associated with −0.14(0.04), −0.12(0.06), and −0.16(0.05) ms² decrease in total, daytime, and nighttime HF, respectively. No associations were found between sleep duration, or sleep efficiency and HRV.ConclusionHigher habitual sleep duration variability and efficiency variability are associated with lower HRV and higher HR, suggesting that an irregular sleep pattern has an adverse impact on CAM, even in healthy adolescents.     

Captopril blocks the cardiac actions of centrally administered angiotensin I in the trout Oncorhynchus mykiss

The present study was performed in order to gain new insights into the existence of a brain renin-angiotensin system (RAS) in teleost fish. For this purpose, we investigated the effects of centrally administered angiotensin (ANG) I ([Asn(1),Val(5),Asn(9)]ANG I) and ANG II ([Asn(1),Val(5)]ANG II) on heart rate (HR) and heart rate variability (HRV) in the unanesthetized trout. The animals were studied before and after treatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor. Trout were equipped with two subcutaneous electrocardiographic electrodes and with an intracerebroventricular (i.c.v.) cannula inserted within the third ventricle of the brain. The i.c.v. injection of vehicle had no effect on the recorded parameters. The i.c.v. injections of ANG I and ANG II at doses of 5 and 50 pmol had a marked effect on HR and HRV. At a dose of 50 pmol, ANG I and ANG II produced a progressive and significant increase in HR (+36% and+45%, respectively) but elicited a profound decrease in HRV (-88% and-92%, respectively). I.c.v. injection of captopril (10 microg) had no effect on HR or HRV. However, this ACE inhibitor prevented the tachycardia and abolished the decrease in HRV mediated by 50 pmol of ANG I. In contrast, captopril had no effect upon the cardiac actions of 50 pmol of ANG II. These results give the first support for the existence of functional important ACE-like activity in the brain of a teleost fish and suggest that the brain RAS in this class of vertebrate may be involved in the control of cardiac chronotropic activity.     

Estimating cardiac autonomic activity during sleep: impedance cardiography, spectral analysis, and Poincaré plots.

OBJECTIVE: To compare noninvasive measures of cardiac autonomic activity during sleep. METHODS: The absolute and normalized (n.u.) high and low frequency peaks from the spectral analysis of R-R intervals (HF, LF, HFn.u., LFn.u.), LF/HF ratio, pre-ejection period (PEP) from impedance cardiography, and the autocorrelation coefficient (rRR) as illustrated in Poincaré plots were measured during night-time sleep in 9 young healthy subjects. Heart rate and blood pressure were also recorded. RESULTS: Heart rate was significantly associated with cardiac sympathetic activity (PEP, average r=-0.46), but not with cardiac parasympathetic activity (HF, average r=-0.17). rRR was significantly associated with heart rate (average r=0.41), and LF/HF (average r=0.69), but not with PEP or HF. From NREM to REM sleep, heart rate, LFn.u., LF and rRR significantly increased, HFn.u. significantly decreased, LF/HF showed an increasing trend (P=0.07) and PEP showed a decreasing trend (P=0.06). Blood pressure and HF were highly variable without significant changes from NREM to REM sleep. CONCLUSIONS: Cardiac parasympathetic activity (HF) does not vary greatly between sleep stages. Cardiac sympathetic activity (PEP) decreases linearly during sleep. rRR and LF/HF can track sympathovagal changes during sleep, but cannot differentiate between changes in cardiac parasympathetic and sympathetic activity. The relative advantages and disadvantages of the different measures are discussed.     

Nighttime cardiac sympathetic hyper-activation in young primary insomniacs

Purpose

A growing literature supports the association between insomnia and cardiovascular risk. Since only few studies have provided empirical evidence of hyper-activation of the cardiovascular system in insomniacs, the aim of the present study was to analyze cardiac autonomic responses in primary insomnia.

Methods

Impedance cardiography and heart rate variability (HRV) measures were assessed in 9 insomniacs and 9 good sleepers during a night of polysomnographic recording.

Results

Insomniacs were found to be characterized by a constant sympathetic hyper-activation which was maintained all night, as suggested by a faster pre-ejection period (PEP) compared to good sleepers. In addition, only insomniacs showed a strong reduction in heart rate in the transition from wake to sleep. Both groups exhibited a reduction in cardiac output and sympathovagal balance, i.e., reductions in low-frequency/high-frequency ratio and increases in high-frequency normalized units of HRV, across the night. In addition, in our sample, a high physiological sympathetic activation (fast PEP) at night was found to be directly associated with low quality of sleep.

Conclusions

These preliminary findings suggest that a constant cardiac sympathetic hyper-activation throughout the night is a main feature of primary insomnia. Our evidences support the association between insomnia and increased risk for cardiovascular diseases.     

Predictive value of heart rate in treatment of major depression with ketamine in two controlled trials

ObjectiveKetamine has been shown to be effective in treatment of episodes of major depressive disorder (MDD). This controlled study aimed to analyse the predictive and discriminative power of heart rate (HR) and heart rate variability (HRV) for ketamine treatment in MDD.MethodsIn 51 patients, HR and HRV were assessed at baseline before and during ketamine infusion and 24 hours post ketamine infusion. Montgomery–Åsberg Depression Rating Scale (MADRS) was used to assess changes of depressive symptoms. A 30% or 50% reduction of symptoms after 24 hours or within 7 days was defined as response. A linear mixed model was used for analysis.ResultsKetamine infusion increased HR and HRV power during and after infusion. Responders to ketamine showed a higher HR during the whole course of investigation, including at baseline with medium effect sizes (Cohen’s d = 0.47–0.67). Furthermore, HR and HRV power discriminated between responders and non-responders, while normalized low and high frequencies did not.ConclusionThe findings show a predictive value of HR and HRV power for ketamine treatment. This further underlines the importance of the autonomous nervous system (ANS) and its possible malfunctions in MDD.SignificanceThe predictive power of HR and HRV markers should be studied in prospective studies. Neurophysiological markers could improve treatment for MDD via optimizing the choice of treatments.     

Pharmacologic responses and spectral analyses of spontaneous fluctuations in heart rate and blood pressure in SHR rats.

The aim of this experiment was to characterize patterns of autonomic control in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats by measuring effects of pharmacologic blockers and using power spectral analysis of heart rate variability (HRV) and blood pressure variability (BPV). Resting HRs and BPs were recorded during a 20-min baseline period and over two 20-min periods of sequential autonomic blockade. On one day, animals received atropine followed by atenolol and on the following day, the drug order was reversed. Power spectrum analyses were performed on 30-s blocks of data throughout each of the three 20-min treatment periods (baseline, single blocker, combined blockade) and HRV and BPV were computed over low and high frequency bands. Increases in HR after atropine were significantly (approx. 40%) smaller in SHR rats than in WKYs. This held true even when animals were pretreated with atenolol. In contrast, decreases in HR following atenolol were similar in the two strains. These results indicate that SHRs have reduced vagal tone, but similar cardiac sympathetic tone compared to WKY rats. Virtually all HRV, over both low and high frequency bands, and in both strains, was inhibited by atropine. SHRs had significantly less high frequency HRV which is consistent with the conclusion that they have reduced cardiac vagal activity when compared with WKYs. BPV was not affected by atropine or atenolol but was inhibited by an alpha-receptor (phentolamine). BPV within both the low and high frequency bands was significantly greater in SHRs, suggesting that sympathetic tone to the vasculature is greater in SHR rats.     

Altered psychobiological reactivity but no impairment of emotion recognition following stress in adolescents with non-suicidal self-injury

Impairments in both stress regulation and emotion recognition have been associated with borderline personality disorder (BPD) and non-suicidal self-injury (NSSI). Although it has been proposed that emotion recognition deficits particularly emerge during stress, this hypothesis has not been fully investigated. Adolescents with and without NSSI performed emotion recognition tasks before and after the employment of the Trier Social Stress Test (TSST). The psychobiological stress response was captured with psychological self-reports (affect, stress and dissociation), physiological recordings (heart rate, HR, and heart rate variability, HRV) and endocrinological sampling of saliva (cortisol and alpha-amylase). Mixed-linear models were applied to analyze stress-induced changes in emotion recognition performance and respective stress response measures. The TSST elicited altered psychobiological stress responses in adolescents with NSSI: A more pronounced decrease in positive affect, a more pronounced increase in negative affect, a less pronounced increase in HR, a less pronounced decrease in HRV and a more pronounced increase in alpha-amylase throughout the stress induction than adolescents without NSSI. Stress responses (dissociation, negative affect, cortisol and HR) differed as a function of BPD severity on a continuum, illustrating greater reactivity on self-reports but decreased biological responsiveness in those with greater BPD severity. Stress induction had similar effects on emotion recognition in adolescents with and without NSSI. Recognition sensitivity and recognition speed equally increased, in the absence of any differences in recognition accuracy. In contrast to prominent propositions, psychosocial stress does not appear to account for impaired emotion recognition across the BPD spectrum.

     

Varying postprandial abdominovagal and cardiovagal activity in normal subjects

Background Several studies have supported the hypothesis of different presentations in the autonomic nervous system (ANS) between cardiac and gastric vagal activity. Due to the regionality of the ANS, different responses among different organ systems to the same stimulation (such as a meal) are quite possible. Methods In this study we monitored the postprandial changes of heart rate variability (HRV) and gastrointestinal (GI) hormones to determine whether both responded in a similar pattern. Twenty‐two healthy volunteers (6 males and 16 females) were enrolled. After recording a baseline ECG rhythm, further recordings were made at 20 min intervals for 120 min after a test meal. Serum human pancreatic polypeptide (PP), leptin, and total and active ghrelin levels were measured. Key Results After the meal, HR increased significantly from baseline at each time point, except for 20 min after the meal. The high frequency (HF) power decreased significantly from 40 min to 120 min after the meal. In addition, the low frequency (LF) power also decreased significantly from 60 min to 120 min. However, the LF : HF ratio increased significantly from 20 min to 120 min. There was a marked increase (>2 fold) of PP at 20 min after the meal, and the increase was sustained throughout the test period. Conclusions & Inferences These findings suggest that HRV reflects cardiac, but not equivalently, abdominovagal activity. Therefore, HRV as an abdominovagal activity measurement in patients with GI functional problems should be used with caution, and other markers such as PP should be included.     

Low-dose atropine amplifies cardiac vagal modulation and increases dynamic baroreflex function in humans

It has been previously known that low-dose atropine (LDA) enhances vagal outflow to the heart. To demonstrate the importance of vagal cardiac modulation in arterial blood pressure (ABP) stability, we evaluated the effect of vagal cardiac stimulation with administration of LDA on ABP fluctuation during dynamic hypertensive and hypotensive stimuli. We assessed changes in RR interval (RRI), ABP, power spectral densities of heart rate variability (HRV) and ABP variability, and spontaneous baroreflex sensitivity (BRS) in 16 healthy volunteers before and after administration of LDA (2 microg/kg). Transient hypertension was induced by phenylephrine (2 microg/kg), whereas hypotension was induced by bilateral thigh cuff deflation after a 3-min suprasystolic occlusion. LDA elicited bradycardia and significantly increased high-frequency (HF, 0.15-0.4 Hz) power of HRV and spontaneous BRS, as determined by transfer function analysis. The increase in systolic blood pressure (SBP) after phenylephrine administration was significantly attenuated by LDA (16+/-2 to 11+/-3 mmHg, P<0.005) and was associated with the augmented reflex bradycardia, whereas the decrease in SBP after cuff deflation was not affected (14+/-5 to 13+/-5 mmHg) with the augmented reflex tachycardia. Increases of HF HRV were correlated significantly and negatively with the increased SBP induced by phenylephrine before and after LDA (r=-0.502, P<0.05). These data suggest that the increased vagal cardiac function induced by LDA augments HR buffering effects, and is important in minimizing arterial pressure fluctuation during dynamic hypertensive stimuli.