Does climacteric status impact regulation of the autonomic nervous system at the age of 46 years?

OBJECTIVE: To investigate whether an earlier-onset climacteric phase is associated with autonomic imbalance at the age of 46 years. METHODS: This cross-sectional birth cohort study included 2661 women aged 46 years. Participants were divided into climacteric (n = 359) and preclimacteric (n = 2302) groups based on menstrual history and follicle stimulating hormone values. The mean heart rate (HR), low-frequency (LF) power, high-frequency (HF) power and LF/HF ratio were analyzed from heart rate variability recordings. The variables were compared between the groups using multivariable linear regression models, including body mass index, smoking and physical activity. The effects of hormone therapy and hot flashes on autonomic function were evaluated in sub-analyses. RESULTS: Climacteric women had a lower mean HR in seated (71.9 ± 10.5 vs. 72.6 ± 10.4 bpm, p = 0.015) and standing (81.2 ± 12.8 vs. 83.6 ± 12.1 bpm, p = 0.002) positions compared to preclimacteric women, and the differences remained significant after the adjustments. In the sub-analyses, more frequent hot flashes were associated with a lower LF power and LF/HF ratio in the sitting position. CONCLUSIONS: The present study suggested an association between greater parasympathetic activation in women with more advanced climacteric status at the age of 46 years.

Three-year outcomes related to coronary stenting; a registry-based real-life population study.

Objectives. Developments in medication and coronary interventions have improved coronary artery disease (CAD) treatment. We studied long-term outcomes in an observational, real-life population of CAD patients undergoing percutaneous coronary intervention (PCI) depending on the presentation and the stent type used. Design and results. Register included 789 consecutive patients undergoing PCI. Follow up period was three years with primary composite outcome (MACE) of all cause -mortality, myocardial infarction and target lesion revascularization. Mean age was 65 ± 11 and 69% were male. New-generation drug-eluting stents (DES-2) were associated with lower adjusted rates of MACE (HR 0.47; 95% CI 0.29-0.77) but not mortality (HR 0.50; 95% CI 0.22-1.14) in comparison to bare-metal stents. Patients with STEMI (14.4%) or NSTEMI (13.7%) had higher crude mortality rates than those with unstable (4.5%) or stable CAD (3.1%; p < .001). The association diminished after adjustments in NSTEMI (HR 2.01; 95% CI 0.88-4.58). Among smokers 45% quitted and 36% achieved recommended cholesterol levels. Conclusions. The overall prognosis was good. Irrespective of comorbidities, NSTEMI was not associated with worse outcome than stable CAD. DES-2 was associated with lower rates of MACE than BMS without affecting mortality rate. Patients succeeded better in smoking cessation than reaching recommended cholesterol levels.

Economic evaluation of exercise-based cardiac rehabilitation in patients with a recent acute coronary syndrome.

Health care decision-making requires evidence of the cost-effectiveness of medical therapies. We evaluated the cost-effectiveness of exercise-based cardiac rehabilitation (ECR) implemented according to guidelines. All the patients (n = 204) had experienced a recent acute coronary syndrome and were randomized to a 1-year ECR (n = 109) or usual care (UC) group (n = 95). The patients' health-related quality of life was followed using the 15D instrument and health care costs were collected from electronic health registries. The cost-effectiveness of ECR was estimated based on intervention and health care costs and quality-adjusted life years (QALYs) gained. The total average cost per patient was lower in ECR than in UC. The incremental cost was divided by the baseline-adjusted incremental QALYs (0.045), yielding an incremental cost-effectiveness ratio of -€24511/QALYs. A combined endpoint of mortality, recurrent coronary event, or hospitalization for a heart failure occurred for five patients in ECR and 16 patients in UC (HR 3.9, 95% CI 1.4-10.6, P = 0.004, relative risk reduction 73%, number needed to treat eight). ECR is a dominant treatment option and decreases the occurrence of adverse cardiac events. These results are useful for decision-making when planning optimal utilization of resources in Finnish health care.

Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized. METHODS AND RESULTS: The correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyceride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E') (p < 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E') and Vitamin D levels was significant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis. CONCLUSIONS: Low Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome.

Temporal dynamics of the circadian heart rate following low and high volume exercise training in sedentary male subjects.

PURPOSE: Increased risk of arrhythmic events occurs at certain times during the circadian cycle with the highest risk being in the second and fourth quarter of the day. Exercise improves treatment outcome in individuals with cardiovascular disease. How different exercise protocols affect the circadian rhythm and the associated decrease in adverse cardiovascular risk over the circadian cycle has not been shown. METHODS: Fifty sedentary male participants were randomized into an 8-week high volume and moderate volume training and a control group. Heart rate was recorded using Polar Electronics and investigated with Cosinor analysis and by Poincaré plot derived features of SD1, SD2 and the complex correlation measure (CCM) at 1-h intervals over the 24-h period. RESULTS: Moderate exercise significantly increased vagal modulation and the temporal dynamics of the heart rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007 respectively). High volume exercise had a similar effect on vagal output (p = 0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the circadian heart rate displays a shift in the acrophage following moderate and high volume exercise from before waking (1st quarter) to after waking (2nd quarter of day). CONCLUSIONS: Our results suggest that exercise shifts vagal influence and increases temporal dynamics of the heart rate to the 2nd quarter of the day and suggest that this may be the underlying physiological change leading to a decrease in adverse arrhythmic events during this otherwise high-risk period.

Autonomic Function Predicts Fitness Response to Short-Term High-Intensity Interval Training.

We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6×30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre-training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT.

Altered relationship between R-R interval and R-R interval variability in endurance athletes with overtraining syndrome.

Autonomic dysfunction decreases within-subject correlation between R-R interval length (RRi) and vagally mediated RRi variability in cardiac disease. We tested the hypothesis that overtraining syndrome (OTS) may also weaken this relationship. Nine OTS and 10 control endurance athletes underwent 24-h electrocardiogram monitoring, which was repeated in eight OTS and nine control athletes after 6 months, when two OTS athletes still had symptoms of OTS. The power of high-frequency (HF) oscillations of RRi was analyzed in 5-min epochs over the whole recording. Quadratic regression was performed between 5-min values of RRi and log-transformed (ln) HF to obtain R(2) for each recording. The relationship between RRi and HFln was higher in the OTS athletes than controls [R(2): 0.87 (90% confidence interval, CI: 0.84-0.89) vs 0.78 (90% CI: 0.72-0.84); P = 0.034; effect size = 1.22]. Large decrease in R(2) was observed in six recovered OTS athletes after 6 months follow-up [ΔR(2): -0.12 (90% CI: -0.25-0.01); P = 0.11; effect size = 1.44] with no changes in the controls. Mean values of RRi and its variability did not differ between the groups. The within-subject correlation between RRi and vagally mediated RRi variability was stronger in endurance athletes with OTS compared with controls. The present findings may improve the detection of OTS and recovery from OTS in endurance athletes.

Characteristics of women with ischemic sudden cardiac death.

BACKGROUND: Sudden cardiac death (SCD) is a significant mode of death causing 15-20% of all deaths in high-income countries. Coronary artery disease (CAD) is the most common cause of SCD in both sexes, and SCD is often the first manifestation of underlying CAD in women. This case-control study aimed to determine the factors associated with SCD due to CAD in women. METHODS: The study group consisted of women with CAD-related SCD (N = 888) derived from the Fingesture study conducted in Northern Finland from 1998 to 2017. All SCDs underwent medicolegal autopsy. The control group consisted of women with angiographically verified CAD without SCD occurring during the 5-year-follow-up (N = 610). To compare these groups, we used medical records, autopsy findings, echocardiograms, and electrocardiograms (ECGs). RESULTS: Subjects with SCD were older (73.2 ± 11.3 vs. 68.8 ± 8.0, p < 0.001) and were more likely to be smokers or ex-smokers (37.1% vs. 27.6%, p = 0.045) compared to control patients. The proportion of subjects with prior myocardial infarction (MI) was higher in controls (46.9% vs. 41.4% in SCD subjects, p = 0.037), but in contrast, SCD subjects were more likely to have underlying silent MI (25.6% vs. 2.4% in CAD controls, p < 0.001). Left ventricular hypertrophy (LVH) was more common finding in SCD subjects (70.9% vs. 55.1% in controls, p < 0.001). Various electrocardiographic abnormalities were more common in subjects with SCD, including higher heart rate, atrial fibrillation, prolonged QTc interval, wide or fragmented QRS complex and early repolarization. The prevalence of Q waves and T inversions did not differ between the groups. CONCLUSIONS: Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with CAD-related SCD. These results suggest that untreated CAD with concomitant myocardial disease is an important factor in SCD in women.

Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with ischemic SCD.Untreated CAD with concomitant myocardial disease is an important factor in SCD among women.Improvements in the diagnosis and management of ischemic cardiomyopathy are likely to reduce the SCD burden in women.

Augmented reality glasses as a new tele-rehabilitation tool for home use: patients' perception and expectations.

MATERIALS AND METHODS: A qualitative approach was employed to track perspectives from a range of patients with chronic lung and/or heart diseases. COPD, IPF and MI outpatients from Denmark and Finland were invited to participate. Data were collected through focus group and semi-structured in-depth interviews. Qualitative analysis was performed using standard thematic analytical approaches. A topic guide was used to explore experiences and perceptions of the ARG telerehabilitation device among participants. RESULTS: Thirteen patients (4 MI, 2 IPF and 7 COPD), 3 women and 10 men aged 56 to 75 years (mean age 63.3 years) were allocated into one focus group (9 patients) and 4 interviews (4 patients). Twelve patients reported the added value of ARG and suggested constructive changes such as the adjustable screen/brightness, robust head fixation for exercise performance, easy to navigate interface and supported feedback based on exercise performance. CONCLUSION: Patients with chronic heart or lung diseases described the added value in an ARG telerehabilitation programme. Improvements for a future version of the ARG were suggested.IMPLICATIONS FOR REHABILITATIONPatients with chronic pulmonary and heart diseases have difficulties to change behaviour to a more active and healthy lifestyle, offers from the health sector to participate in rehabilitation programmes at the hospital are feasible and improves quality of life and exercise capacity. Not all the patients are capable of participating in such rehabilitation programmes due to frailty and long distance to the hospital. Telerehabilitation seems to be a potential treatment to cope with the needs expressed above.Patient involvement in the development of a telerehabilitation solution to empower chronic pulmonary and heart patients to train, ensures a positive contribution to the design of the expected augmented reality software and hardware envisioned solution for telerehabilitation.The development of a user-centered telerehabilitation platform responding to the preferences of patients with chronic disease will remove barriers that limit use and compliance and improve empowerment in future research projects.

Abnormalities in beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction.

OBJECTIVES: The purpose of this research was to study possible abnormalities in the beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction. BACKGROUND: Analysis of approximate entropy of time series data provides information on the complexity of both deterministic and random processes. It has been proposed that regularity or loss of complexity of RR interval dynamics may be related to pathologic states, but this hypothesis has not been well tested in cardiovascular disorders. METHODS: Approximate entropy and conventional time and frequency domain measures of RR interval variability were compared between 40 healthy subjects with no evidence of heart disease and 40 patients with coronary artery disease and a previous Q wave myocardial infarction. The groups were matched with respect to age, and cardiac medication was discontinued in the patients with coronary artery disease before the 24-h electrocardiographic recordings. RESULTS: Approximate entropy was significantly higher in the postinfarction patients (1.21 +/- 0.18 [mean +/- SD]) than in the healthy subjects (1.05 +/- 0.11, p < 0.001), whereas the standard deviation of RR intervals (63 +/- 19 vs. 86 +/- 23 ms, p < 0.001) and the very low, low and high frequency spectral components were lower (p < 0.01, p < 0.001, p < 0.05, respectively). Approximate entropy was not related to the time domain or the spectral components of heart rate variability and was more commonly abnormal in postinfarction patients (62.5%) than any linear measure (from 20% to 42.5%) when the 90% percentile of the values obtained for healthy subjects was defined as the normal range for each measure. CONCLUSIONS: Despite reduced linear measures of heart rate variability, the unpredictability or randomness of beat to beat heart rate dynamics is increased in patients with a previous myocardial infarction. Complexity analysis of RR interval dynamics may provide useful information on abnormalities in heart rate behavior that are not easily detected by the commonly used moment statistics.

Dynamic analysis of heart rate may predict subsequent ventricular tachycardia after myocardial infarction.

Dynamics analysis of RR interval behavior and traditional measures of heart rate variability were compared between postinfarction patients with and without vulnerability to ventricular tachyarrhythmias in a case-control study. Short-term fractal correlation of heart rate dynamics was better than traditional measures of heart rate variability in differentiating patients with and without life-threatening arrhythmias.

Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts.

The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

Effect of cardiac vagal outflow on complexity and fractal correlation properties of heart rate dynamics.

1. Cardiac vagal outflow is the major factor determining the magnitude of heart rate (HR) variability analysed by traditional time and frequency domain methods. New analysis techniques, such as fractal and complexity methods, have been developed to probe non-linear features in HR behaviour that may not be detectable by traditional methods. 2. We investigated the effects of vagal blockade (glycopyrrolate i.v. 5 microg kg-1 h-1 for 2 h, n = 8 vs. unmedicated control group, n = 8) and various breathing patterns (n = 12) on two non-linear measures of HR variability--detrended fluctuation analysis (DFA) and approximate entropy (ApEn)--in healthy male volunteers. 3. Glycopyrrolate decreased the mean (+/-SD) ApEn from 1.46 +/- 0.18 to 0.85 +/- 0.24 (P = 0.001 in comparison with the control group), and increased the short-term (alpha 1) and intermediate-term (alpha 2) fractal scaling exponents of DFA, alpha 1 from 0.96 +/- 0.19 to 1.43 +/- 0.29 (P = 0.003) and alpha 2 from 1.13 +/- 0.10 to 1.34 +/- 0.14 (P < 0.001). 4. Decrease in fixed respiration rate from 15 to 6 breaths min-1 increased alpha 1 from 0.83 +/- 0.25 to 1.18 +/- 0.27 (P < 0.001), but decreased alpha 2 from 0.88 +/- 0.09 to 0.45 +/- 0.17 (P < 0.001) and ApEn from 1.26 +/- 0.12 to 1.10 +/- 0.14 (P = 0.028). Rapid breathing (24 min-1) had no influence on these non-linear measures of HR variability. Hyperventilation (15 min-1, tidal volume increased voluntarily by 0.5 l) decreased alpha 1 from 0.83 +/- 0.25 to 0.66 +/- 0.28 (P = 0.002) but did not affect alpha 2 or ApEn. 5. To conclude, vagal blockade alters the fractal scaling properties of R-R intervals (alpha 1, alpha 2) and reduces the complexity (ApEn) of HR behaviour. Both the fractal and complexity measures of HR variability can also be influenced by changes in the breathing pattern.

Non-alpha-adrenergic effects on systemic vascular conductance during lower-body negative pressure, static exercise and muscle metaboreflex activation.

AIM: This study tested the hypothesis that non-α-adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex-specific manner during the sympathoexcitatory manoeuvres. METHODS: Twelve healthy subjects underwent lower-body negative pressure (LBNP, -40 mmHg) as well as static handgrip exercise (HG, 20% of maximal force) followed by post-exercise forearm circulatory occlusion (PECO, 5 min each) with and without α-adrenergic blockade induced by phentolamine (PHE). Aortic blood flow, finger blood pressure and superficial femoral artery blood flow were measured to calculate cardiac output, SVC and leg vascular conductance (LVC) during the last minute of each intervention. RESULTS: Mean arterial pressure (MAP) decreased more during LBNP with PHE compared with saline (-7 ± 7 vs. -2 ± 5%, P = 0.016). PHE did not alter the MAP response to HG (+20 ± 12 and +24 ± 16%, respectively, for PHE and saline) but decreased the change in MAP during PECO (+12 ± 7 vs. +21 ± 14%, P = 0.005). The decrease in SVC and LVC with LBNP did not differ between saline and PHE trials (-13 ± 10 vs. -17 ± 10%, respectively, for SVC, P = 0.379). In contrast, the SVC response to HG increased from -9 ± 12 with saline to + 5 ± 15% with PHE (P = 0.002) and from -16 ± 15 with saline to +1 ± 16% with PHE during PECO (P = 0.003). LVC responses to HG or PECO were not different from saline with PHE. CONCLUSIONS: Non-α-adrenergic vasoconstriction was present during LBNP. The systemic vasoconstriction during static exercise and isolated muscle metaboreflex activation, in the absence of leg vasoconstriction, was explained by an α-adrenergic mechanism. Therefore, non-α-adrenergic vasoconstriction is more emphasized during baroreflex, but not metaboreflex-mediated sympathetic activation.

Heart rate dynamics during accentuated sympathovagal interaction.

Concomitant sympathetic and vagal activation can occur in various physiological conditions, but there is limited information on heart rate (HR) behavior during the accentuated sympathovagal antagonism. Beat-to-beat HR and blood pressure were recorded during intravenous infusion of incremental doses of norepinephrine in 18 healthy male volunteers (mean age 23 +/- 5 yr). HR and blood pressure spectra and two-dimensional Poincaré plots were generated from the baseline recordings and from the recordings at different doses of norepinephrine. The mean blood pressure increased (from 90 +/- 7 to 120 +/- 9 mmHg, P < 0.001), HR decreased (from 60 +/- 9 to 48 +/- 7 beats/min, P < 0.001), and the high-frequency spectral component of HR variability increased (P < 0.001) during the norepinephrine infusion as evidence of accentuated sympathovagal interaction. Abrupt aperiodic changes in sinus intervals that were not related to respiratory cycles or changes in blood pressure occurred in 14 of 18 subjects during the norepinephrine infusions. These fluctuations in sinus intervals resulted in a complex or parabola-shaped structure of the Poincaré plots of successive R-R intervals and a widening of the high-frequency spectral peak. In four subjects, the abrupt fluctuations in sinus intervals were followed by a sudden onset of fixed R-R interval dynamics with a loss of respiratory modulation of HR, resulting in a torpedo-shaped structure of the Poincaré plots. These data show that HR behavior becomes remarkably unstable during accentuated sympathovagal interaction, resembling stochastic dynamics or deterministic chaotic behavior. These features of HR dynamics can be better identified by dynamic analysis of beat-to-beat behavior of R-R intervals than by traditional analysis techniques of HR variability.

Vagal modulation of heart rate during exercise: effects of age and physical fitness.

This study was designed to assess the effects of age and physical fitness on vagal modulation of heart rate (HR) during exercise by analyzing the instantaneous R-R interval variability from Poincaré plots (SD1) at rest and at different phases of a bicycle exercise test in a population of healthy males. SD1 normalized for the average R-R interval (SD1n), a measure of vagal activity, was compared at rest and during exercise among subjects of ages 24-34 (young, n = 25), 35-46 (middle-aged, n = 30), and 47-64 yr (old, n = 25) matched for peak O2 consumption (VO2 peak) and among subjects with VO2 peak of 28-37 (poor, n = 25), 38-45 (average, n = 36), and 46-60 ml.kg-1.min-1 (good, n = 25) matched for age. SD1n was higher at rest in the young subjects than in the middle-aged or old subjects (39 +/- 14, 27 +/- 16, and 21 +/- 8, respectively; P < 0.001), but the age-related differences in SD1n were smaller during exercise [e.g., 11 +/- 5, 9 +/- 5, and 8 +/- 4 at the level of 100 W; P = not significant (NS)]. The age-matched subjects with good, average, and poor VO2 peak showed no difference in SD1n at rest (32 +/- 17, 28 +/- 13, and 26 +/- 11, respectively; P = NS), but SD1n differed significantly among the groups from a low to a moderate exercise intensity level (e.g., 13 +/- 6, 10 +/- 5, and 6 +/- 3 for good, average, and poor fitness groups, respectively; P < 0.001, 100 W). These data show that poor physical fitness is associated with an impairment of cardiac vagal function during exercise, whereas aging itself results in more evident impairment of vagal function at rest.

Quantitative beat-to-beat analysis of heart rate dynamics during exercise.

Beat-to-beat heart rate (HR) dynamics were studied by plotting each R-R interval as a function of the previous R-R interval (Poincaré plot) during incremental doses of atropine followed by exercise for 10 subjects and during exercise without autonomic blockade for 31 subjects. A quantitative two-dimensional vector analysis of a Poincaré plot was used by measuring separately the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) and the standard deviation of continuous long-term R-R interval variability (SD2) as well as the SD1/SD2 ratio. Quantitative Poincaré measures were compared with linear measures of HR variability (HRV) and with approximate entropy (ApEn) at rest and during exercise. A linear progressive reduction was observed in SD1 during atropine administration, and it remained almost at the zero level during exercise after a parasympathetic blockade. Atropine resulted in more variable changes in SD2 and the SD1/SD2 ratio, but during exercise after parasympathetic blockade, a progressive increase was observed in the SD1/SD2 ratio until the end of exercise. The SD1/SD2 ratio had no significant correlations with the frequency domain measures of HRV. However, the SD1/SD2 ratio had a modest correlation with ApEn at rest (r = -0.69, P < 0.001), but not during exercise (r = 0.27, P = NS). All measures of vagal modulation of HR decreased progressively until the ventilatory threshold level was reached, when sympathetic activation was reflected as changes in the SD1/SD2 ratio. These results show that quantitative two-dimensional vector analysis of a Poincaré plot can provide useful information on vagal modulation of R-R interval dynamics during exercise that are not easily detected by linear summary measures of HRV or by ApEn.

Differences in autonomic modulation of heart rate during arm and leg exercise.

Heart rate (HR) is higher during dynamic arm exercise than during leg exercise at equal oxygen consumption levels, but the physiological background for this difference is not completely understood. The vagally mediated beat-to-beat R-R interval fluctuation decreases until the level of approximately 50% of maximal oxygen consumption during an incremental bicycle exercise, but the vagal responses to arm exercise are not well known. Changes in autonomic modulation of HR were compared during arm and leg exercise by measuring beat-to-beat R-R interval variability from a Poincaré plot normalized for the average R-R interval (SD1n), a measure of vagal activity, in 14 healthy male subjects (age 20 +/- 4 years) who performed graded bicycle and arm cranking tests until exhaustion. Seven of the subjects also performed the dynamic arm and leg tests after beta-adrenergic blockade (propranolol 0.2 mg kg-1 i.v.). More rapid reduction occurred in SD1n during the low-intensity level of dynamic arm exercise than during dynamic leg exercise without beta-blockade (e.g. 11 +/- 6 vs. 20 +/- 10 at the oxygen consumption level of 1.2 l min-1; P < 0.001) and with beta-blockade (e.g. 13 +/- 4 vs. 25 +/- 10 at the level of 1.0 l min-1; P < 0.05), and the mean HR was significantly higher during submaximal arm work than during leg work in both cases (e.g. during beta-blockade 81 +/- 12 vs. 74 +/- 6 beats min-1 at the level of 1.0 l min-1; P < 0.05). These data show that dynamic arm exercise results in more rapid withdrawal of vagal outflow than dynamic leg exercise.

Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamics.

Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics.