Effect of Continuous and Intermittent Exercises on Oxidised HDL and LDL Lipids in Runners.

We studied the effects of different types of exercises on the concentrations of oxidised HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum lipids, antioxidant potential, paraoxonase and malondialdehyde in endurance runners by performing both a 40-min continuous run (velocity corresponding to 80% VO2max) and a 40-min intermittent run (2-min run, velocity corresponding to 100% VO2max, and 2-min rest) using a treadmill. Blood samples were taken before exercise, after 20 and 40 min of exercise, and 15 and 90 min after the end of exercise. The concentrations of oxLDLlipids remained unchanged during the running tests, but after a 90-min recovery the concentrations decreased by 4% (P<0.05) for the intermittent run and by 16% (P<0.01) for the continuous run. The acute effect of the intermittent and continuous run increased the concentrations of oxHDLlipids by 26 and 25%, respectively (P<0.001 for both). Interestingly, oxHDLlipids did not increase after the first half of the run in middle-distance runners during the intermittent run, and a similar phenomenon was seen in marathon runners during the continuous run. These results may indicate that acute physical exercise increases the transport of lipid oxidation products by HDL, although a different training history or genetic background may alter these acute responses.

Decreased training volume and increased carbohydrate intake increases oxidized LDL levels.

We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-ß-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruited for a randomized, double-blind intervention during which they received either Lactobacillus rhamnosus GG (LGG, probiotic group) or placebo drink (placebo group) during whole study. During the preparation period, subjects decreased training and increased carbohydrate intake. Blood samples were taken at baseline, before 6-days preparation, before and immediately after the marathon. Probiotics did not have any effect on ox-LDL, s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively (in all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s-TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level during the preparative period after several months' training suggests that aerobic training may reduce the concentration of ox-LDL and that decrease of training together with increased energy intake, mainly carbohydrate, before marathon is capable of increasing the level of ox-LDL.

Heart-rate variability and SIDS. Examination of heart-rate patterns using an expert system generator.

In a prospective, population-based study, HRV was analyzed from 24-hr tape recordings made on 16 full-term and one preterm infant who had subsequently suffered SIDS and compared to similar data on 23 control infants (n of recordings, 44). In the SIDS group, heart rate was higher, and overall and beat-to-beat HRV (CV, CVS, respectively) were lower, than in the controls, but not significantly. Respiratory rate and respiratory HRV (by spectral analysis) were similar in both groups. Assuming that cardiorespiratory mechanisms of SIDS are multifactorial, we expected that several subgroups would be detected in both test groups. Therefore, the average data for each recording were subsequently examined by means of an expert system generator (ExTran, Intelligent Terminals Ltd., Edinburgh, UK). By rules induced with 25 nodes, the following results were obtained: 16/44 recordings were diagnosed as SIDS on the basis of (1) respiratory rate (RR) less than 33 and CV less than 3.46% (n = 8); (2) RR greater than 33, CVS less than 2.18%, and BW greater than 3,520 g (n = 4); and (3) RR greater than 33, CVS less than 2.18%, BW less than 3,520 g, HR greater than 136, and CV greater than 1.89% (n = 4). Seventeen of 44 were considered as non-SIDS when (1) RR was 33-47.4, CVS greater than 2.18%, and RSA less than 74.3 and (2) RR greater than 33, CVS less than 2.18%, BW less than 3,520 g, and HR less than 142. The remaining 11 cases required more complicated rules in order to be classified. This study shows that although the trend of increased HR and decreased HRV in the SIDS cases was statistically non-significant, an expert system program may be helpful in defining decision rules to identify cases of SIDS on the basis of cardiorespiratory data.

Association of abnormal flow velocity waveforms in the uterine artery with frequency-specific fetal heart rate variability.

The aim of the study was to determine if abnormal flow velocity waveforms in the uterine artery are associated with altered frequency-specific fetal heart rate variability (HRV). Fetuses in the last third of gestation were studied. In seven fetuses the pulsatility index (PI) of the blood flow velocity waveform in the uterine artery was increased (Group II), and in ten fetuses the PI was normal (Group I). Frequency-specific HRV (0.025-0.07 Hz, 0.07-0.13 Hz, 0.13-1.0 Hz) was quantified by power spectral analysis and correlated with the PI in the uterine artery, umbilical artery and the middle cerebral artery. The slow variability dominated the fetal HRV. There was no difference between the groups in the mean frequency-specific variability. In Group II, an increase of the PI in the umbilical artery and a decrease in the middle cerebral artery correlated with an increase of HRV, the increase being greatest at the lowest frequency band.

Heart rate variability in infants subsequently suffering sudden infant death syndrome (SIDS).

To study the role of the autonomic cardiovascular control in SIDS the heart rate variability (HRV) was analysed from 24 tape recordings made from a prospective population-based study on 16 term and one preterm infant suffering SIDS and compared to similar data on 23 control infants matched on birthweight, gestation and postnatal age. The number of regular breathing segments was lower in the SIDS cases than in controls (P = 0.02). No significant differences were found between the SIDS cases and their controls for average heart rate, median breathing rate, indices of overall and beat-to-beat HRV. Neither were significant intergroup differences found when the subjects were divided into neonatal and postneonatal subgroups. Analysis of HRV by power-spectral techniques did not show any significant differences between SIDS cases and controls for the general distribution of power or for the respiratory HRV. Analysis of HRV did not differentiate infants destined to die of SIDS from surviving controls in the same population.

Cerebral circulation assessed by transcephalic electrical impedance during the first day of life--a potential predictor of outcome?

Pulsatile changes in intracranial blood volume (transcephalic electrical impedance, delta Z), arterial blood pressure (aBP) and respiration were studied during the first day after birth in 42 neonates with a birth weight of 1040-3850 g and gestational age of 26-36 weeks. The neurological outcome was assessed at 1 year of age to study the predictive ability of delta Z. delta Z, ECG, respirogram and direct aBP were recorded at 8-h intervals. Outcome was adverse in seven infants of whom two died from severe peri-intraventricular haemorrhage. PCO2 was higher (6.2 kPa) in the infants with adverse outcome than in those infants with favourable outcome (5.0 kPa) (P = 0.004). Blood glucose (4.5 vs. 3.3 mmol/l, P = 0.030) and first day administration of fluid (80 vs. 63 ml/kg/day, P = 0.003) behaved, respectively. Of the infants receiving dopamine therapy, 60% had adverse outcome while only 11% of those not receiving dopamine had adverse outcome (P = 0.016). Of the infants with high diastolic blood pressure levels, 32% had adverse outcome, while none with low diastolic blood pressure levels had adverse outcome (P = 0.031). Spectral analysis was used to examine signal variabilities in the frequency domain. During the first 24 h of life, the variabilities of aBP and respiration were equal in all the infants. The high-frequency delta Z signal variability (1.50-4.00 Hz, heart rate level) was found to be lower in the infants with adverse outcome (330 units) than in the infants with favourable outcome (1280 units, P = 0.017). The low delta Z variability allowed us to assume that there is a decrease of pulsatile cerebral blood flow (CBF) in the infants with adverse outcome. We speculate that this may result from the 'no reflow phenomenon', increased tissue pressure due to ischaemia and/or PIVH, the 'brain sparing effect' or constriction of main cerebral arteries due to increased pressure support or metabolic factors (PCO2, glucose). We believe that transcephalic impedance provides a potential cot-side method for monitoring cerebral circulation in the neonatal period with an ability to predict outcome.

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.

Multivariate autoregressive modelling combined with transcephalic electrical impedance: method to relate neonatal systemic circulation and respiration to cerebral circulation.

We studied the pulsatile component of cerebral circulation with transcephalic electrical impedance (delta Z) in six preterm newborns, three of whom had severe cerebral bleeding, peri-intraventricular haemorrhage (PIVH). The transcephalic electrical impedance delta Z signal, ECG, arterial blood pressure, (aBP) and respirogram were recorded on analogue magnetic tape for 30 min. Artefact-free stationary segments (lasting for 2 min) of the four signals were digitised. A digital multivariate autoregressive (MAR) model was used to study frequency-specific variability in the signals and to quantify interrelations between the variabilities of delta Z, HR, aBP and respiratory signals. MAR modelling describes a system where all the signals simultaneously explain each other. The inherent variability of delta Z was lower and the influences of respiration and aBP on delta Z significantly greater in infants with severe PIVH than in controls. These changes were observed at high frequencies corresponding to respiration and heart rate. This may be interpreted as a marker of pressure passivism in the cerebral circulation following PIVH. We conclude that in preterm babies the application of MAR modelling, together with transcephalic impedance, may be a new, helpful and quantitative method for the study of simultaneous interrelations between variables of cerebral and systemic circulations and respiration.

Computer analysis of heart rate variation and breathing movements in fetal lambs.

A quantitative method for studying the frequency-specific relationships between heart rate (HR) and fetal breathing movements (FBM) was developed. The reactivity of periodic HR variation in relation to FBM was investigated by means of power spectral analysis. Seven fetal lambs were studied during the third trimester of gestation using a chronic animal model. HR variability increased at the rate of FBM, as shown by an increase of spectral density at > 0.35 Hz in the HR autospectrum and in the cross-spectrum of HR and respirogram, as well as by an increase in the short-term variability index CVS. FBM were associated with the increased HR variation in all but the lowest frequency bands (0.07-1.0 Hz). Although respiratory sinus arrhythmia was found, only 10 per cent of the total HR variability and 25 per cent of the joint-density of HR and respirogram appeared at > 0.35 Hz during FBM. The greatest variation in both the HR and respirogram spectra appeared at < 0.07 Hz. Although the low-frequency variability of HR and respirogram was simultaneous, it was on the whole not synchronised. The existence of multiple control systems that simultaneously link the cardiac and respiratory control mechanisms to each other in the fetal lamb is postulated.

Beta-adrenergic control and inter-relationships between heart rate and blood pressure in neonatal lambs.

Our aim was to develop a signal analysis method for revealing interrelationships between heart rate and blood pressure and for displaying the influence of autonomic nervous control on these signals in a chronic lamb model. A chronically instrumented neonatal lamb model was made to record ECG and direct arterial blood pressure (N = 15). Continuous two-minute recordings of blood pressure (BP) and ECG were digitised. The instantaneous heart rate signal (IHR) was derived from the ECG. The IHR and BP signals were bandpass filtered. Autospectra, cross-spectra, coherence spectra and phase spectra for the signals were computed to study the relative magnitudes and inter-relationships of the cardiovascular signals under normal conditions and during beta-adrenergic blockade. It was noted that both in the BP and IHR there were oscillations at the frequency of less than 0.1 Hz and also at the respiratory rate around 0.6 Hz. Beta-blockade reduced the oscillations of the IHR in less than 30-day-old lambs. It did not affect the coherence spectra or the phase lag between the signals. During quiet sleep the variability of blood pressure was decreased. In over-30-day-old-lambs the beta-blockade did not affect the variabilities of the cardiovascular parameters. These findings indicate that in neonatal lambs the sympathetic control system is a major regulator of cardiovascular interactions.

Spectral analysis of impedance respirogram in newborn infants.

Respiratory rate (RR), transthoracic electric impedance (TEZ) and transcutaneous PO2 and PCO2 were monitored during the 5 first postnatal days in 54 neonates on three separate occasions. There was no difference in the overall RR between the term and healthy preterm babies on different days of recordings but RR of the babies with RDS (who were all ventilated) was lower on day 1 (p less than 0.01). When the power spectrum of the TEZ respirogram was computed and the spectral density was divided into low-frequency (LF, less than 0.20 Hz) and high-frequency (HF, greater than 0.20 Hz) areas, the LF/HF ratio of healthy preterm babies was greater than that of term babies on day 1 (p less than 0.01). The preterm babies with RDS did not differ from the term babies in this respect. The LF/HF ratio was negatively correlated with gestational age and it had a positive correlation to PtcO2 (p less than 0.05) and PtcCO2 (p less than 0.01) (R2 = 0.07). The result evidences that the control of respiration changes in relation to maturity and the LF/HF ratio is a quantitative indicator of respiratory variability reflecting this development.

Intraesophageal pressure monitoring and the severity of respiratory distress syndrome.

The intraesophageal pressure difference (delta Pes) was measured in 46 preterm infants, 36 with respiratory distress (RDS). It was 12.7 +/- 2.9 mm Hg (mean +/- SEM) in severe RDS, 9.6 +/- 3.2 mm Hg in moderate RDS, and 5.2 +/- 1.6 mm Hg in infants with mild disease, measured at the age of 8 h. These intergroup differences were highly significant (P less than 0.001). During the first 96 h of life the delta Pes decreased to 6.1 +/- 1.1 mm Hg in severe RDS and to 4.8 +/- 1.2 mm Hg in moderate RDS. These changes were also highly significant (P less than 0.001) when compared with respective initial values. In infants with mild disease and in healthy preterm infants, the delta Pes did not alter significantly during the first 96 h of life. The correlations between gastric aspirate L/S ratio and the delta Pes at the age of 8 h (r = -0.65, P less than 0.001) and at the age of 24 h (r = -0.73, P less than 0.001) were highly significant. It is concluded that intraesophageal pressure monitoring is a valuable tool in the intensive care evaluation of the severity of RDS.

Continuous cerebral electrical impedance monitoring in sick preterm infants.

Cerebral electrical impedance (dZ) and intra-arterial blood pressure were measured continuously during the first 48 h after birth in 26 sick ventilated preterm infants with a birth weight less than 1500 g. The aim was to establish whether any patterns of dZp or the variability of either blood pressure or dZp would allow identification of those infants who developed intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) or a poor neurological outcome. IVH and PVL were diagnosed by ultrasound image obtained every 6 h. Cerebral electrical impedance recordings were unsuitable for analysis in three patients and a further three died within 14 h of birth. In the remaining 20 patients, no step changes that may have been related to the onset of IVH or PVL were evident and whilst three patterns of dZp were identified, they were not useful in distinguishing between normal infants or those who developed IVH, PVL or had a poor neurological outcome. Using multiple linear regression, the coefficient of variation of dZp was significantly associated with both IVH and outcome, as was the coefficient of variation of blood pressure. Continuous measurement of cerebral electrical impedance, whilst technically feasible in sick preterm infants, was not found useful as a method of identifying those who developed IVH, PVL or had a poor neurological outcome.

Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy.

Reduced respiratory sinus arrhythmia, measured as heart rate variability, is a reliable indicator of autonomic nervous dysfunction, reflecting a damage in vagal cardiac control. The authors studied the heart rate variability (HRV) of nine children treated for acute lymphoblastic leukemia during the different phases of cytostatic treatment utilizing heart rate processing techniques with a computer. The indices of HRV as well as the spectral components of heart rate were examined with special relation to vincristine administration. The heart rate variability was significantly reduced during the vincristine induction phases as compared to the consolidation and maintenance phases without vincristine administration. In particular, the respiratory components of the HRV during deep breathing tests were significantly reduced during vincristine treatment. The authors conclude that the measurement of the HRV is a suitable method for monitoring transient autonomic neuropathy, which these results show to be a frequent complication of vincristine treatment.

Elevated arterial blood pressure is associated with peri-intraventricular haemorrhage.

UNLABELLED: In a prospective study, brain ultrasound scans were performed in 42 newborns (median birth weight 1700 g, range 1020-3720 g; gestational age 32 weeks, 26-36) to reveal peri-intraventricular haemorrhage (PIVH) (grades I-IV) as well as echodensities (ED) and/or periventricular leucomalacia (PVL). ECG and arterial blood pressure were recorded on magnetic tape at 8-h intervals during the first 24 h of life for further computer analysis. Heart rate (HR) and its variability (HRV) indices RMSM (long-term variability) and RMSSD (short-term variability), together with their coefficients of variation, were computed. Systolic (SBP), diastolic (DBP), and mean blood pressures (MBP) were detected as average values for 2-min stationary segments together with the respective minima and maxima. The indices of variability and their coefficients of variation were computed for the arterial pressure. PIVH was found in 12 newborns and ED in 8 (of whom two developed PVL). The remaining 22 served as controls. Neither HR, HRV nor BP variability differed between the groups. DBP was higher in the group with PIVH (39 mmHg) when compared to both the controls (33 mmHg, P < 0.05) and the ED group (32 mmHg, P < 0.01). MBP behaved respectively (45 mmHg, 38 mmHg, 37 mmHg, P < 0.01). SBP behaved also similarly when gestational age and birth weight were used as covariates (57 mmHg, 48 mmHg, 47 mmHg, P < 0.01). CONCLUSION: Our results suggest that elevated diastolic, mean and systolic blood pressure are significantly associated with peri-intraventricular haemorrhage in preterm newborn infants.

Heart rate variation in relation to age and sleep state in neonatal lambs.

The heart rate (HR), heart rate variation (HRV) and the power spectrum of the HR were studied in 1 to 10-week-old neonatal lambs. The average HR was highest and the indices of the HRV were lowest at the age of 1 to 3 weeks. However, there was a decreasing trend in the overall HRV with advancing age when it was normalized in relation to the average HR. The absolute beat-to-beat HRV increased after the age of 3 weeks; it remained the same when normalized in relation to the HR. The overall HRV was highest during waking and active sleep; it was lowest during quiet sleep. The beat-to-beat HRV was lower during quiet sleep than during active sleep. Three major peaks of HRV power were detected in the spectra of all lambs. During active sleep the HRV power increased at all frequencies ranging from 0 to 1.0 Hz. During waking the low-frequency HRV power was primarily increased. The high-frequency HRV was pronounced during quiet sleep and the state of sleepy waking, especially at the age of 4 to 6 weeks. Our study indicates that developmental factors and the sleep state have to be considered when HR patterns are experimentally investigated. Many similarities between the HR control of neonatal lambs and that of human neonates make it feasible to study the mechanisms of clinical HRV patterns by lamb experiments.

Do beta-adrenergic blockade and sleep state affect cardiorespiratory control in neonatal lambs? Multivariate autoregressive modeling approach.

Beta-Blockers are used in pregnancy-associated hypertension and in postnatal cardiac arrhythmias, and the neonate may get them in breast milk. We therefore studied the effects of beta-adrenergic medication on interrelations between heart rate (HR), respiration, and arterial blood pressure (aBP) in newborn lambs. The influence of sleep state on these cardiorespiratory interrelations was also examined. HR, aBP, and respiration (based on transthoracic electrical impedance) were recorded and the sleep state was visually documented in five healthy chronically instrumented newborn lambs before the age of 30 d. Propranolol was given (1 mg/kg). Two-min stationary segments of the three signals were analyzed using a multivariate autoregressive model, which yields oscillations of the signals and intersignal relationships as source contributions. The variabilities of aBP and HR were greatest at the low frequencies (less than 0.25 Hz) and so were their intersignal relationships (including baroreflex). The respiratory variability was greatest at the frequencies corresponding to the respiratory rate. During quiet sleep, the variabilities in HR, aBP, and respiration were lowest. The impact of respiratory oscillations on other signals increased but the impact of aBP variability decreased during quiet sleep. beta-Blockade and sleep state affected separately the cardiovascular and respiratory variables and their interrelations. beta-Blockade reduced HR and increased pulse pressure. The overall heart rate variability and the respiratory low-frequency contribution to heart rate variability decreased due to the beta-blockade. We postulate that the beta-adrenergic system is an important regulator of HR and HR variability in neonatal lambs and also of the low-frequency components of the respiratory sinus arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Tracking of serum lipoprotein (a) concentration and its contribution to serum cholesterol values in children from 7 to 36 months of age in the STRIP Baby Study. Special Turku Coronary Risk Factor Intervention Project for Babies.

We investigated the tracking phenomenon of serum lipoprotein (a) concentrations and assessed the impact of serum concentration of lipoprotein (a) cholesterol on total cholesterol concentrations in children from 7 to 36 months of age. Serum samples for lipoprotein (a) and cholesterol determinations at 7, 13, 24 and 36 months were prospectively obtained from 430 children. Serum lipoprotein (a) was determined using immunoradiometric assay. A strong correlation was observed between lipoprotein (a) concentrations at 7 and 36 months of age (r = 0.88, P < 0.001). Seventy-eight per cent to 86% of the children in the lowest and highest lipoprotein (a) quintiles at 13 months remained in the respective quintiles at 36 months. The average contribution of lipoprotein (a) cholesterol to total cholesterol varied from 0.5% to 3.2% (individual variation 0.13-32.39%) depending on the type of milk received and the age of the children. At 7 months the contribution was 0.44% in breast-fed and 0.93% in formula-fed infants (P < 0.0001). The tracking phenomenon of serum lipoprotein (a) concentrations is strong already in early childhood. The contribution of lipoprotein (a) cholesterol to serum total cholesterol concentration should be taken into account when the changes in serum cholesterol levels are interpreted in the first year of life.

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.

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.