Human baroreflex rhythms persist during handgrip and muscle ischaemia.

AIM: To determine whether physiological, rhythmic fluctuations of vagal baroreflex gain persist during exercise, post-exercise ischaemia and recovery. METHODS: We studied responses of six supine healthy men and one woman to a stereotyped protocol comprising rest, handgrip exercise at 40% maximum capacity to exhaustion, post-exercise forearm ischaemia and recovery. We measured electrocardiographic R-R intervals, photoplethysmographic finger arterial pressures and peroneal nerve muscle sympathetic activity. We derived vagal baroreflex gains from a sliding (25-s window moved by 2-s steps) systolic pressure-R-R interval transfer function at 0.04-0.15 Hz. RESULTS: Vagal baroreflex gain oscillated at low, nearly constant frequencies throughout the protocol (at approx. 0.06 Hz - a period of about 18 s); however, during exercise, most oscillations were at low-gain levels, and during ischaemia and recovery, most oscillations were at high-gain levels. CONCLUSIONS: Vagal baroreflex rhythms are not abolished by exercise, and they are not overwhelmed after exercise during ischaemia and recovery.

Comparison of vagal baroreflex function in nonpregnant women and in women with normal pregnancy, preeclampsia, or gestational hypertension.

OBJECTIVE: Our aim was to compare baroreflex function among nonpregnant women and among women with normal pregnancy, preeclampsia, or gestational hypertension. STUDY DESIGN: Baroreflex function was tested in 20 women with preeclampsia, in 20 age- and gestational age-matched normotensive gravid women, in 20 age-matched nonpregnant women, and in 20 nonmatched women with gestational hypertension. The baroreflex was measured by several modalities. RESULTS: Vagal baroreflex gain measured by cross-spectral analysis of parallel spontaneous heart rate and blood pressure changes is significantly decreased in normal pregnancy (15.8 +/- 7.2 vs 10.8 +/- 4.1 ms/mm Hg; P = 0.001), in comparison with vagal baroreflex gain in nonpregnant women. Baroreflex gain is further reduced in preeclamptic pregnancy (10.8 +/- 4.1 vs 7.2 +/- 2.6 ms/mm Hg; P = 0.003) and in gestational hypertension (10.8 +/- 4.1 vs 6.5 +/- 2.7 ms/mm Hg; P = 0.001), compared with that in normal pregnancy. Similar differences were seen with other baroreflex testing modalities. CONCLUSIONS: The normal reduction of baroreflex gain in pregnancy is further depressed in subjects with hypertensive disorders of pregnancy.

Respiratory modulation of human autonomic rhythms.

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

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 ms/mmHg 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.

Nine months in space: effects on human autonomic cardiovascular regulation.

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

Cardiac positron emission tomography imaging with [11C]hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure.

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [11C]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head-up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF.

Effects of tocolytic treatment with ritodrine on cardiovascular autonomic regulation.

OBJECTIVE: To study the acute effects of tocolytic treatment with intravenous ritodrine on cardiovascular autonomic regulation. DESIGN: Validated methods to assess cardiovascular autonomic nervous function-heart rate and blood pressure variability and vagal cardiac baroreflex sensitivity-were measured before and during ritodrine infusion. SETTING: Turku University Central Hospital, Turku, Finland. SAMPLE: Twelve pregnant women admitted to hospital for threatened preterm labour. METHODS: Electrocardiogram and continuous noninvasive finger blood pressure signals were recorded in each woman, resting in a supine position. Autoregressive spectrum analysis was used to quantify short term heart rate and blood pressure variability. Vagal cardiac baroreflex sensitivity was measured as the bradycardia response to an intravenous bolus injection of phenylephrine. MAIN OUTCOME MEASURES: Vagal cardiac baroreflex sensitivity and spectrum analysis indices of short term heart rate and blood pressure variability. RESULTS: Ritodrine significantly decreased vagal cardiac baroreflex sensitivity as well as total (0.00-0.40 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power bands of the heart rate variability spectrum. Ritodrine significantly increased mean heart rate and the low frequency power band of the systolic blood pressure variability spectrum. CONCLUSIONS: In pregnant women with threatened preterm labour intravenous administration of ritodrine decreases vagal cardiac baroreflex sensitivity and vagal modulation of heart rate, and increases sympathetically mediated blood pressure variability. Decreased baroreflex sensitivity and heart rate variability are known to be associated with a poor prognosis in some patient groups, so the effects of ritodrine tocolysis may be unfavourable in women with impaired circulatory homeostasis.

Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine.

We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

Human responses to upright tilt: a window on central autonomic integration.

1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Heart rate variability and occurrence of ventricular arrhythmias during balloon occlusion of a major coronary artery.

Experimental studies suggest that autonomic mechanisms are important in the genesis of ischemia-induced malignant ventricular arrhythmias, but the role of the autonomic nervous system in human arrhythmogenesis is not well known. To assess whether heart rate variability (HRV) predicts the occurrence of ventricular arrhythmias during acute coronary artery occlusion, we performed continuous electrocardiographic, heart rate, and blood pressure recordings before and during a 2-minute balloon occlusion of a stenotic coronary artery in 252 patients with no baseline ventricular premature complexes (VPCs). The ranges of nonspecific responses in heart rate and blood pressure were determined by analyzing a control group of 19 patients with no ischemia during a 2-minute balloon inflation in a totally occluded coronary artery. Balloon occlusion of a coronary artery was stopped because of complex, i.e., bigeminal or repetitive, VPCs in 14 patients, and solitary (<5) VPCs were observed in an additional 19 patients. During coronary occlusion, HRV increased (p <0.001) and heart rate decreased (p <0.05) in patients with no VPCs, whereas an opposite tendency to reduction in HRV (p = 0.08) was observed in patients with complex VPCs. Complex VPCs were observed in 5 (42%) of the 12 patients with a significant coronary occlusion-induced decrease in HRV, in 7 (3.5%) of 200 patients with no change in HRV, but in none of the 40 patients with a significant increase in HRV (p <0.001). Baseline HRV did not predict the occurrence of VPCs during coronary occlusion. Logistic regression analysis identified the decrease in HRV (p <0.001) to be the only independent predictor of complex VPCs. In conclusion, coronary occlusion-induced increase in HRV seems to protect against occurrence of complex ventricular arrhythmias during the early phase of abrupt coronary occlusion, suggesting that vagal activation may modify the outcome of acute coronary events in patients with coronary artery disease.

Arterial baroreflex impairment in patients during acute coronary occlusion.

OBJECTIVES: We tested whether acute coronary occlusion interferes with arterial baroreceptor control of heart rate in humans. BACKGROUND: Subnormal baroreflex sensitivity (BRS) is an important risk indicator for sudden death. Animal research indicates that both chronic myocardial infarction and acute coronary occlusion impair baroreflex modulation of heart rate. METHODS: We measured RR interval prolongation after phenylephrine-induced systolic pressure increases before and during 2-min coronary occlusions in 47 patients (27 men) undergoing clinically indicated single-vessel coronary angioplasty for stenoses in the proximal or midportion of the vessel causing >50% reduction in the arterial diameter, with normal antegrade flow (33 anterior descending, 10 circumflex, 4 right coronary artery). A control group of 11 patients treated for chronic total occlusion of a coronary artery was assessed to evaluate nonspecific changes in baroreflex function during a 2-min balloon inflation in the occluded artery. RESULTS: The BRS decreased from 5.2+/-3.8 (mean+/-SD) to 4.1+/-3.5 ms x mm Hg(-1) (p=0.01) during the coronary occlusion in the 28 patients with preserved arterial baroreceptor control of heart rate-that is, adequate blood pressure responses and correlation coefficients of the slopes both in baseline and during coronary occlusion. The same phenylephrine dose increased systolic pressure less during than before coronary artery occlusion (21+/-21 versus 36+/-16 mm Hg, p < 0.0001), and in 6 patients it failed to prevent systolic pressure reduction during occlusion. Correlation coefficients of the baroreflex regressions decreased from 0.81+/-0.27 to 0.47+/-0.44 (p < 0.0001) during coronary artery occlusion in the 41 patients with adequate systolic pressure rises in both phenylephrine tests, and the association between RR intervals and rising systolic pressures was lost in 13 patients during coronary occlusion. Balloon inflation in a chronic total occlusion of a coronary artery did not cause significant changes in BRS (from 5.3+/-4.0 to 5.2+/-3.7 ms x mm Hg(-1)), correlation coefficient of the slope or phenylephrine-induced pressure rise. CONCLUSIONS: Our study shows that abrupt coronary occlusion impairs baroreflex modulation of vagal and sympathetic nervous outflow in humans.

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 micrograms 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 micrograms 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.

Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Low-dose transdermal scopolamine decreases blood pressure in mild essential hypertension.

BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have antihypertensive effects. Low-dose transdermal scopolamine increases vagal-cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects and in cardiac patients. OBJECTIVE: To study the short-term effects of transdermal scopolamine on blood pressure and cardiovascular autonomic control in patients with mild essential hypertension. DESIGN: A randomized, double-blind, placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5 years (mean+/-SD)] patients with mild essential hypertension. METHODS: We recorded the electrocardiogram, auscultatory sphygmomanometric and continuous photoplethysmographic finger arterial pressure, and spirometry signals with patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing. Cardiovascular autonomic regulation was analyzed with power spectrum analysis of R-R interval and arterial pressure variability and a spontaneous sequence method for baroreflex sensitivity. In addition, a deep-breathing test was performed to assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal scopolamine treatment significantly decreased blood pressure both when patients lay supine and when they were in the 70 degrees tilted position. Scopolamine also slowed heart rate and increased baroreflex sensitivity and R-R interval high-frequency variability for both body positionings. In addition, scopolamine accentuated respiratory sinus arrhythmia during deep breathing and blunted the tilt-induced increase in heart rate. Scopolamine did not affect blood pressure variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure, increases baroreflex sensitivity and accentuates vagal-cardiac modulation of sinus node in patients with mild hypertension. Our study supports the hypothesis that increasing cardiovascular parasympathetic activity could have antihypertensive effects in essential hypertension.

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

The dose-response effects of terbutaline on the variability, approximate entropy and fractal dimension of heart rate and blood pressure.

AIMS: To study the dose-response effects of intravenous terbutaline on the cardiovascular and respiratory autonomic nervous regulation. METHODS: The study followed a randomized, placebo-controlled crossover design in six healthy adult volunteers. The terbutaline dose ranged from 10 to 30 microg min(-1) We continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions at baseline and during 3 h drug infusion. The periodic variability components of R-R intervals (time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. The regularity of the time series was assessed by approximate entropy (ApEn) and the convolutedness by fractal dimension (FD). RESULTS: Terbutaline dose-dependently decreased total variability of R-R intervals, low frequency (LF) variability of R-R intervals (10 s waves), high frequency (HF) variability of R-R intervals (respiratory variability), total variability of SAP, HF variability of SAP, baroreflex sensitivity, plasma potassium concentration, approximate entropy of R-R interval and of SAP as well as fractal dimension of R-R interval. Terbutaline dose-dependently increased heart rate, LF/HF ratios of R-R intervals and of SAP, LF variability of SAP, minute ventilation and plasma terbutaline concentration. CONCLUSIONS: Terbutaline infusion decreases parasympathetic cardiovascular reactivity, baroreflex sensitivity, dimensionality of heart rate and plasma potassium concentration; it increases sympathetic dominance in cardiovascular autonomic balance, minute ventilation, and the regularity of heart rate and blood pressure time series.

Gender difference in autonomic and hemodynamic reactions to abrupt coronary occlusion.

OBJECTIVES: We sought to determine whether there are gender-related differences in autonomic and hemodynamic responses to abrupt coronary occlusion. BACKGROUND: The risk of sudden death before hospital admission is higher in men with an acute myocardial infarction. The reasons for this gender-related difference are not well understood. Cardiovascular autonomic regulation modifies the outcome of acute coronary events, and there are gender differences in the autonomic regulation of heart rate (HR) in normal physiologic circumstances. METHODS: We analyzed the changes in HR, HR variability and blood pressure and the occurrence of ventricular ectopic beats during a 2-min coronary occlusion in 140 men and 65 women referred for single-vessel coronary angioplasty. The ranges of nonspecific responses were determined by analyzing a control group of 19 patients with no ischemia during a 2-min balloon inflation in a totally occluded coronary artery. RESULTS: Women more often had ST segment changes (p < 0.01) and chest pain (p < 0.05) during the occlusion. Significant bradycardia or increase in HR variability as a sign of vagal activation occurred more often in women than in men (31% vs. 13%, p < 0.01 and 25% vs. 11%, p < 0.05, respectively). Coronary occlusion also more often caused (28% vs. 11%, p < 0.01) a decrease in blood pressure in women. The most pronounced female preponderance was in the incidence of Bezold-Jarisch-type reaction (i.e., simultaneous bradycardia and decrease in blood pressure [16% vs. 0.7%, p < 0.0001]). Logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia identified female gender to be an independent predictor of bradycardic reactions (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.7, p < 0.01), hypotensive reactions (OR 2.6, 95% CI 1.1 to 6.0, p < 0.05) and Bezold-Jarisch-type response (OR 22.2, 95% CI 2.5 to 200, p < 0.01). Significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats emerged as having borderline significance (OR 0.4, CI 0.1 to 1.1, p = 0.07). CONCLUSIONS: Vagal activation is more common in women than in men during abrupt coronary occlusion and may have beneficial antiarrhythmic effects, modifying the outcome of acute coronary events.

Altered cardiovascular autonomic regulation after 2-week inhaled salbutamol treatment in asthmatic children.

UNLABELLED: We studied the effects of therapeutic 2-week inhaled salbutamol treatment on the cardiovascular and respiratory autonomic nervous regulation in eight children with asthma. In this randomized, double-blind, placebo-controlled crossover study our test subjects inhaled 200 microg salbutamol or placebo thrice daily for 14 days. After the 14-day treatment we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline and the response to a single 600 microg salbutamol inhalation. The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis. Two-week salbutamol treatment increased baseline low frequency (LF) variability (P < 0.05) and low frequency/high frequency (LF/HF) variability ratio of R-R intervals (P < 0.05) when compared to the placebo treatment. As a response to the single salbutamol inhalation the increase in LF/HF ratio of R-R intervals was smaller after the 2-week salbutamol treatment (P < 0.01). No significant differences were found in the bronchodilatory response after the treatment period. CONCLUSION: Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. Because these effects were evident 18 h after cessation of the therapy they are likely to reflect the adaptation of organ responses to regular therapy or altered central autonomic regulation rather than direct drug effect. A slight tolerance developed in the sympathovagal cardiac response but not in the bronchodilatory response.

Baroreflex sensitivity in drug-treated systemic hypertension.

Baroreflex sensitivity is impaired in patients with systemic hypertension. The persistence of abnormal baroreflex sensitivity despite adequate blood pressure control may be one of the reasons why the effect of antihypertensive therapy on coronary artery disease mortality has been less than expected on the basis of the achieved blood pressure levels.