Nitroglycerin induced syncope occurs in subjects with delayed phase shift of baroreflex action

Nitroglycerin (NTG) administration occasionally leads to syncope due to severe hypotension and bradycardia. This reaction resembles neurocardiogenic syncope but it may occur when the patient is in the supine position. To address the possible role of prevailing autonomic tone and baroreflex control in precipitation of NTG induced syncope, continuous noninvasive blood pressure and an ECG were taken shortly before NTG application in the supine position. Frequency-domain measures of heart rate variability (HRV) and noninvasive indices of baroreflex were compared between subjects who did (n = 6) and did not (n = 41) develop syncope after NTG. Both groups differed only in the phase shift (P(CR)) between oscillations of blood pressure and heart rate during controlled respiration (0.1 Hz). P(CR) was significantly delayed in subjects who developed syncope than in controls (- 99.3+/-14.1 vs -65.5+/-27.0 degrees, P = 0.002). Thus, subjects with prolonged P(CR) are prone to NTG induced syncope because of increased lagging and, consequently, less stable baroreflex control.     

Autonomic responses to the Valsalva manoeuvre in healthy subjects

Summary. To assess normal autonomic haemodynamic responses to the Valsalva manoeuvre, 158 healthy unmedicated subjects, aged 25–60 years, were examined. For measurement of beat-to-beat blood pressure on a finger, the Finapres instrument was used. Phase-to-phase changes in instantaneous blood pressure and heart rate and the latency response between the end of a Valsalva manoeuvre and points on the resultant blood pressure and heart rate were calculated, and the reference limits for various indices were determined. Sex had no or only marginal effect on blood pressure or heart rate responses or latencies. Ageing was accompanied by a smaller decrease and smaller partial recovery of blood pressure during the strain, with attenuation of reflectory bradycardia, and lengthening of the latencies. It is concluded that age-related reference values should be applied in the interpretation of the Valsalva responses. The following responses should be analysed: mean blood pressure decrease and partial recovery during the strain (adrenergic vasoconstrictor function), reflectory bradycardia after the strain (parasympathetic function), and the latencies (sympathetic and parasympathetic function).     

Effects of age on the cardiac and vascular limbs of the arterial baroreflex

BACKGROUND: Healthy ageing has several effects on the autonomic control of the circulation. Several studies have shown that baroreflex-mediated vagal control of the heart deteriorates with age, but so far there is little information regarding the effect of ageing on sympathetically mediated baroreflex responses. The aim of this study was to assess the effects of ageing on baroreflex control of the heart and blood vessels. MATERIALS AND METHODS: In 40 healthy volunteers, aged 20-87 years, we applied oscillatory neck suction at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was maintained at 0.25 Hz. Blood pressure, electrocardiographic RR intervals and respiration were recorded continuously. Spectral analysis was used to evaluate the magnitude of the low-frequency (0.03-0.14 Hz) and high-frequency (0.15-0.50 Hz) oscillations in the RR interval and blood pressure. Responses to neck suction were assessed as the change in power of the RR interval and blood pressure fluctuations at the stimulation frequency from baseline values. RESULTS: Resting low- and high-frequency powers of the RR interval decreased significantly with age (P < 0.01). However, the low-frequency power of systolic blood pressure did not correlate with age. Spontaneous baroreflex sensitivity (alpha-index) showed a significant inverse correlation with age (r = -0.46, P < 0.05). Responses of the RR interval and systolic blood pressure to 0.1 Hz neck suction stimulation were not related to age, however, the RR interval response to 0.2 Hz neck suction declined significantly with age (r = -0.61, P < 0.01). CONCLUSIONS: These results confirm an age-related decrease in cardiovagal baroreflex responses. However, sympathetically mediated baroreflex control of the blood vessels is preserved with age.     

Effect of non-hypotensive haemorrhage on plasma catecholamine levels and cardiovascular variability in man

Background: It is well known from animal research that non‐hypotensive haemorrhage produces sympathoexcitatory responses assessable by both the rise in plasma catecholamine levels and the shift of autonomic influences on the heart to more sympathetic and less parasympathetic control. Data in humans are restricted. Methods: Heart rate variability (HRV), systolic blood pressure (FINAPRES) variability (BPV), and catecholamine plasma levels were measured before and after haemorrhage in 30 healthy blood donors and compared with those from 10 control subjects without blood loss. Spectral power of HRV and BPV in very low (0·02–0·06 Hz), low (0·07–0·14 Hz), and high (0·15–0·40 Hz) frequency bands were calculated by Fourier analysis. Catecholamine plasma levels were assayed by dual column reverse‐phased high‐performance liquid chromatography (HPLC). Results: Haemorrhage of 5·6 ± 1·2 ml kg^?1 body weight increased plasma norepinephrine levels (215 ± 92 pg ml^?1 versus 254 ± 95 pg ml^?1; P = 0·002), increased BPV in the low frequency band (Mayer waves; 1·8 ± 1·0 ln [mmHg²] versus 2·0 ± 0·9 ln [mmHg²]; P = 0·021), and decreased the vagally transmitted high frequency HRV (6·9 ± 1·1 ln [MI²] versus 6·5±1·2 ln [MI²]; P<0·0001), but did not induce significant changes in heart rate (66 ± 11 bpm versus 67 ± 11 bpm; P = 0·79) and arterial blood pressure (mean values: 84 ± 13 mmHg versus 87 ± 13 mmHg; P = 0·12). Conclusions: As suggested by plasma norepinephrine levels, systolic BPV and HRV, non‐hypotensive haemorrhage produces sympathoexcitatory responses as well as vagal withdrawal of heart rate control in humans.     

Response patterns of arterial pressure and heart period to Mueller manoeuvre and their comparison to those of Valsalva manoeuvre

Objective: It has not been established if the Mueller manoeuvre (MM) induces characteristic arterial pressure (AP) and heart rate changes analogous to those observed during its respiratory strain opposite, the Valsalva manoeuvre (VM). Our aims were to explore, on a beat‐by‐beat basis, if MM evokes well‐defined changes in AP and heart period (HP), and to compare these responses with those of VM. Methods: From the ECG and AP records of 24 healthy subjects who performed VM and MM in sitting position, RR intervals and AP series were computed. The series were ensemble‐averaged, and the characteristic points that limit the phases were semi‐automatically detected from each record. Results: Our main findings were: (i) MM provoked consistent patterned responses in both AP and HP in the same four phases of VM; (ii) the AP and HP changes of MM were parallel to those of VM in phases II and IV, and opposite in direction in phases I and III; (iii) pooled data during the strain and poststrain and the mean characteristic points of AP and HP were smaller in MM than in VM (P<0·001); (iv) MM presented two changes absent in VM, AP and HP rise immediately after phase I and hypotension in late phase IV; (v) systolic pressure and HP presented a strong positive correlation (r = 0·87 ± 0·02) in late phase II of MM. Conclusion: Our study characterizes on a phase‐by‐phase basis the AP and RR interval responses to MM, documents their great similarity to those corresponding to VM and establishes that MM exerts a 50% smaller impact on the cardiovascular autonomic function than VM.     

Effect of beta blockade with and without sympathomimetic activity (ISA) on sympathovagal balance and baroreflex sensitivity

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21–39 years, during controlled frequency breathing (0·30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0·15–0·40 Hz) band (PROP 7·4 ± 1·0; PLA 6·9 ± 1·4; PIN 6·8 ± 1·0 ln MI²; P = 0·003), decreased BPV in the low-frequency band (at 0·1 Hz, Mayer waves) (PROP 0·6 ± 0·7; PLA 1·3 ± 1·1; PIN 1·2 ± 1·2 ln mmHg²; P = 0·001) and enhanced BRS (PROP 14·6 ± 9·5; PLA 8·0 ± 6·8; PIN 8·7 ± 6·8 ms mmHg^?1; P = 0·001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6·1 ± 0·9; PLA 6·5 ± 1·1; PIN 6·9 ± 0·7 ln MI²; P<0·001) and decreased Mayer waves (PROP 1·8 ± 0·8; PLA 2·4 ± 1·0; PIN 2·7 ± 0·8 ln mm Hg²; P<0·001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0·9 ± 1·0; PLA + 0·3 ± 1·3, PROP + 0·3 ± 1·0 ln MI²; P = 0·026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.     

Endurance training,overtraining and baroreflex sensitivity in female athletes

We examined heavy training-induced changes in baroreflex sensitivity, plasma volume and resting heart rate and blood pressure variability in female endurance athletes. Nine athletes (experimental training group, ETG) increased intense training (70–90% VO _2max) volume by 130% and low-intensity training (<70% VO _2max) volume by 100% during 6–9 weeks, whereas the corresponding increases in six control athletes (CG) were 5% and 10% respectively. Maximal oxygen uptake (VO _2max) in the ETG and CG did not change, but in five ETG athletes VO _2max decreased from 53·0 ± 2·2 (mean ± SEM) (CI 46·8–59·2) ml kg^–1 min^–1 to 50·2 ± 2·3 (43·8–56·6) ml kg^–1 min^–1 (P<0·01), indicating overtraining. Baroreflex sensitivity (BRS) measured using the phenylephrine technique and blood pressure variability (BPV) did not change, but the low-frequency power of the R–R interval variability increased in the ETG (P<0·05). The relative change in plasma volume was 7% in the ETG and 3% in the CG. The changes in BRS did not correlate with the changes in plasma volume, heart rate variability and BPV. We conclude that heavy endurance training and overtraining did not change baroreflex sensitivity or BPV but significantly increased the low-frequency power of the R–R interval variability during supine rest in female athletes as a marker of increased cardiac sympathetic modulation.     

Computational and physiological background of the baroreflex sensitivity

All the commonly used definitions of baroreflex sensitivity (BRS) are based on a slope of linear relationship between systolic blood pressure and pulse interval (R–R interval). However, heart rate (HR) and R–R interval bear an inverse non‐linear relationship, which distorts determination of BRS when different HR levels are present. We analysed data of 117 healthy, normal‐weight, non‐smoking men and women aged 23–77 to show how BRS depends on the initial HR. In this data, 43% of variation in BRS is solely explained by HR. Comparisons of BRS between patients with different HR and even within the same patient with changing HR (e.g. tilt‐table test and nocturnal changes in HR) should be questioned. Consideration of the baseline HR is even more crucial, if the patients are subjected to an intervention affecting not only baroreflexes but also HR. If baseline HR is not taken into account, using the R–R interval in the estimation of BRS may lead to partially misleading values and possibly also to misinterpretation of physiological processes. We discuss alternative definitions of BRS to allow varying HRs.     

Effect of acute dose of caffeine on cardiovascular autonomic responses in healthy subjects

Summary. The effect of acute dose of caffeine (4 mg kg^-1) on cardiovascular autonomic responses were studied in 10 healthy subjects. Standard cardiovascular reflex tests were used during which heart rate and blood pressure were continuously measured. Each subject was tested twice in a random order, with and without prior use of caffeine. It was found that immediate heart rate responses following standing up were lower under influence of caffeine. Blood pressures were systematically, although non-significantly, higher and blood pressure responses in isometric handgrip test stronger when caffeine was used before testing. It is suggested that caffeine should not be used before autonomic testing. This is especially important when the test(s) are performed for research purposes or in order to study the blood pressure responses. If the tests are made for diagnostic purposes the following rules should be adopted: (1) if the subject has used caffeine before testing but all heart rate responses are within normal ranges, it can be assumed that the subject does not have cardiac parasympathetic neuropathy and retesting is not necessary; (2) if the patient has used caffeine before testing and the results suggest presence of autonomic neuropathy, the patient must be retested without the prior use of caffeine.     

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.     

Heart rate and blood pressure variability in cardiac diseases: pharmacological implications

Summary— Even at rest, blood pressure and heart rate fluctuate continuously around their mean values. Considerable interest has recently focused on the assessment of spontaneous fluctuations in heart rate and blood pressure, ie, heart rate and blood pressure variability, using time or frequency domain indexes. Heart rate variability has been extensively studied in cardiovascular disease and has emerged as a valuable parameter for detecting abnormalities in autonomic cardiovascular control, evaluating the prognosis and assessing the impact of drug therapy on the autonomic nervous system in patients with myocardial infarction, congestive heart failure or a heart transplant. In contrast, until the recent development of noninvasive methods for continuous blood pressure recording, blood pressure variability received little attention, and this parameter remains to be evaluated in cardiovascular disease.     

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.     

Effects of noradrenaline on human vagal baroreflexes

BACKGROUND. Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function.

AIM. To understand better the role of NA in cardiovascular homeostasis.

METHODS. We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz.

RESULTS. The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (± SD) baseline level of 17.3 ± 6.6 to 34.1 ± 20.8 msJmmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0 ± 12.9 to 10.1 ± 7.4 during the low NA infusion rate and to 6.2 ± 6.2% during the high rate (P < 0.05 and 0.01, respectively).

CONCLUSIONS. Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.     

Effects of local arteriosclerosis on carotid baroreflex sensitivity and on heart rate and arterial pressure variability in humans

The study examined whether the alterations in heart rate variability (HRV) and baroreflex sensitivity (BRS) observed in patients with coronary artery disease can also be discerned in otherwise healthy subjects with mild-to-moderate arteriosclerosis in the carotid artery bifurcation. Based on the results of carotid duplex ultrasonography, subjects were designated as either having no arteriosclerotic lesions (n = 18), unilateral (n = 19) or bilateral lesions (n = 18) in the bifurcation. Electrocardiograms were recorded and simultaneous and continuous records of arterial pressure were obtained. Resting HRV was determined by calculating the spectral power density in three frequency bands: 0-0.05 Hz [very low frequency (VLF) band], 0.05-0.15 [low frequency (LF) band] and 0.15-2 Hz (high frequency band), whereas the arterial pressure variability (APV) was determined from spectral power density of the VLF and LF bands. Carotid BRS was evaluated by measuring R-R intervals during application of pulse-synchronous graded pressures (40 to -65 mmHg) in a neck-chamber device. Analysis of variance revealed no effect of mild-to-moderate carotid arteriosclerosis on the spectral components of HRV and APV or on BRS. It thus appears that mild-to-moderate asymptomatic carotid arteriosclerosis does not affect carotid BRS, APV or HRV at rest.     

Testing of autonomic cardiovascular regulation—methodological considerations

Summary. The different analyses of the results on autonomic nervous function tests were evaluated in 43 male and 32 female diabetic patients and in 24 male and 24 female control subjects, aged 47–67 years, all without any known heart disease. The Valsalva ratio of the first effort did not differ from the mean Valsalva ratio of three efforts. During deep breathing, heart rate variation and max/min R-R interval ratio determined from the first three breathing cycles did not differ from the respective variables calculated from six consecutive breathing cycles. Diastolic blood pressure response to isometric handgrip was greater during the third minute than during the first and the first two minutes. In conclusion, the tests for the evaluation of autonomic nervous function can be simplified without losing their diagnostic value.     

Ankle to arm index response to exercise and heat stress in healthy subjects

Summary. Ankle to arm index (AAI) defined as the ratio of ankle systolic blood pressure (ASBP), to brachial systolic blood pressure is largely used in the study of lower extremity arterial disease (LEAD). To study the hypothesis of the shunt of blood away from the skin as the explanation of AAI decrease in exercise, we studied the AAI and ASBP responses to an increase in cardiac output originating from an increase either in muscle blood flow (exercise) or in cutaneous blood flow (thermal stress Brachial systolic pressure, ankle systolic pressure and heart rate (HR) were measured in 9 healthy subjects at rest, during heat thermal stress and following maximal exercise on a cycle ergometer. Compared to resting values, AAI decreased in all subjects from 1.05 ± 0.07 to 0.75 ± 0.07 (P < 0.05) 1 min following exercise and from 1.08 ± 0.07 to 0.94 ± 0.05 (P < 0.05) during heat stress. On the other hand, HR increased from 72.8 ± 12.2 to 112.4±19.6 (P < 0.05) min following exercise and from 75.5 ± 13.6 to 96.8 ± 15.3 (P < 0.05) during heat stress. Since a comparable relation exists between. AAI and HR in thermal stress and exercise, we suggest that the decrease in AAI in normal subjects following exercise is due to turbulences at high flow levels, rather than the shunting of blood to active muscles in exercise.     

Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure on circulatory adaptation in preterm infants

We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine treatments on the autonomic cardiovascular control in preterm neonates with respiratory distress syndrome during the first 2 days of life. Serial measurements of heart rate (HR), blood pressure (BP) and respirogram were performed during the first 2 days of life in 28 preterm infants below 33 weeks of gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in 12 nonexposed preterm controls. Spectral analysis was used for the quantification of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR or the systolic, diastolic or mean BP, it was associated with significant decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no consistent effects on the autonomic cardiovascular control during the first 2 days of life. Our data suggest that maternal MgSO4 treatment decreases the neonatal high frequency changes in BP. This early vascular stabilizing effect of antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular catastrophes, in the vulnerable areas of the brain, among the preterm infants with respiratory distress syndrome.     

Impact of functional training on cardiac autonomic modulation,cardiopulmonary parameters and quality of life in healthy women

Functional training (FT) promotes benefits in various physical abilities; however, its effect on autonomic modulation, cardiorespiratory parameters and quality of life in the healthy adult population is unknown, and thus, the aim of this study was to evaluate the influence of FT on these variables in healthy young women. The study consisted of 29 women, distributed into two groups: the FT Group (FTG; n = 13; 23 ± 2·51 years; 21·90 ± 2·82 kg m^?²) and the Control Group (CG; n = 16; 20·56 ± 1·03 years; 22·12 ± 3·86 kg m^?²). The FTG performed periodized FT for 12 weeks, three times a week. The following were evaluated: autonomic modulation (heart rate variability), cardiorespiratory parameters and quality of life (SF‐36 Questionnaire). The Student's t‐test for unpaired data or the Mann–Whitney test was used to compare the differences obtained between the final moment and the initial moment of the studied groups (P<0·05). The FTG demonstrated significant improvements in quality of life and autonomic modulation (P<0·05), but not in the cardiorespiratory parameters. Functional training was able to produce improvements in autonomic modulation and quality of life.     

Altered cardiovascular autonomic regulation after salmeterol treatment in asthmatic children

The effects of therapeutic 4 weeks' inhaled salmeterol treatment on the cardiovascular and respiratory autonomic nervous regulation was studied in 11 asthmatic children using inhaled corticosteroid medication. The study followed a randomized, double-blind, placebo-controlled cross-over design. The salmeterol dose was 50 μg twice daily. The 4-week salmeterol treatment increased baseline heart rate, low-frequency/high-frequency (LF/HF) variability ratio of R–R intervals, LF variability of systolic arterial pressure (SAP) and maximum tidal volume during the deep breathing test, as well as morning and evening peak expiratory flow (PEF) values. The 4-week salmeterol treatment decreased baseline HF variability of R–R intervals. As a response to the acute 600 μg of salbutamol, the changes in heart rate, HF variability of R–R intervals and diastolic blood pressure were significantly smaller after 4 weeks' salmeterol treatment. In conclusion, 4 weeks' therapeutic salmeterol treatment decreases basal cardiovagal reactivity, increases sympathetic dominance in the cardiovascular autonomic balance and improves pulmonary function. A tolerance develops in the cardiovascular response but not in the bronchodilatory response.