Péter Studinger

Maturation of Cardiovagal Autonomic Function From Childhood to Young Adult Age

Background—Cardiovagal autonomic control declines with age in adult subjects, which is related in part to increasing stiffness of the barosensory vessel wall. It is not known, however, whether autonomic function changes with age in children. Methods and Results—We studied 137 healthy subjects divided into 4 age groups: group 1, 7 to 14 years; group 2, 11 to 14 years; group 3, 15 to 18 years; and group 4, 19 to 22 years. Brachial artery pressure was measured by sphygmomanometry and continuous radial artery pressure and carotid artery pulse pressure (&Dgr;P) by applanation tonometry. The R-R interval was derived from the ECG. Autonomic function was assessed by spontaneous sequence and frequency-domain indices, which indicate the extent of coupling between fluctuations in heart rate and systolic pressure. Carotid artery diastolic diameter (DD) and pulsatile distension (&Dgr;D) were measured by echo wall tracking; carotid compliance coefficient (CC) was defined as &Dgr;D/&Dgr;P and distensibility coefficient as 2&Dgr;D/DD · &Dgr;P. From group 1 to group 3, spontaneous indices increased significantly (18.1±1.7 versus 33.3±4.0; 14.4±1.1 versus 25.5±22; 12.9±1.1 versus 20.8±2.0; and 6.4±0.6 versus 16.2±1.4 ms/mm Hg [mean±SEM] for Seq+, Seq−, LF&agr;, and LFgain, respectively), with no significant changes afterward. CC and DC were inversely proportional to age (r=−0.49 and −0.62, respectively, P<0.001). The efficiency of neural integrative mechanisms, estimated as the ratio of spontaneous indices and CC, more than doubled from group 1 to group 3. Spontaneous indices were linearly related to measures of cardiac vagal activity. Conclusions—The increase in spontaneous indices from early childhood to adolescence, despite gradual stiffening of the carotid artery, may indicate improved cardiovagal autonomic function, which is most likely a result of maturation of neural mechanisms, attaining peak level at adolescence.

Age‐ and fitness‐related alterations in vascular sympathetic control

In the current study we explored (1) if there were differences in sympathetic activity and baroreflex function by age, sex, or physical activity status, (2) if any aspect of baroreflex function related to differences in resting sympathetic activity, and (3) if mechanical and/or neural baroreflex components related to differences in integrated baroreflex gain. Electrocardiogram, blood pressure, carotid diameter and muscle sympathetic nerve activity were recorded continuously at rest and during sequential bolus injections of sodium nitroprusside and phenylephrine in 22 young, 21 older sedentary and 10 older trained individuals. Analyses of co‐variance were used to examine age, sex and training status differences and to explore the explanatory power of integrated baroreflex gain and its mechanical and neural components. Training status and sex influenced neither resting sympathetic outflow nor sympathetic baroreflex gain components. Older subjects had a smaller mechanical component and a strong tendency towards a greater neural component of the sympathetic baroreflex during both pressure falls and pressure rises. Opposing age‐related changes in mechanical and neural components resulted in a smaller integrated gain during pressure falls, but a greater integrated gain during pressure rises in older subjects. Thus, in older individuals, compromised sympathetic activation to pressure falls was owing to the stiffening of barosensory vessels, whereas the more sensitive sympathoinhibition to pressure rise was due to an increased neural control. Enhanced neural control with age, however, did not contribute the increased resting sympathetic outflow, which indicates that these two changes are probably driven by distinct neural mechanisms.

Mechanical and neural contributions to hysteresis in the cardiac vagal limb of the arterial baroreflex

According to conventional wisdom, hysteresis in cardiac vagal baroreflex function exhibits a specific pattern: pressure falls are associated with longer heart periods and a smaller linear gain. A similar pattern occurs in the pressure–diameter relationship of barosensory vessels, and therefore it has been suggested that baroreflex hysteresis derives solely from vascular behaviour. However, we hypothesized that mechanical and neural baroreflex components contribute equally to baroreflex hysteresis. Blood pressure, carotid diameter and the electrocardiogram were recorded continuously during two trials of sequential bolus injections of nitroprusside and phenylephrine in 14 young healthy subjects. Baroreflex gain and its mechanical and neural components were estimated for falls and rises in pressure and diameter. The position or set point of the relations was quantified at the mean pressure and mean diameter. Gains were determined via piecewise linear regression. Set points and gains for falls versus rises in pressure and diameter were compared with the Chow test. Hysteresis was observed in all individuals, but not in every trial. In most, but not all, trials pressure falls were associated with longer heart periods and smaller linear gain, as conventional wisdom would predict. However, the pattern of hysteresis derived from the interaction of both mechanical and neural components. The two components most often acted in opposition to determine differences in set point, but in conjunction to determine differences in baroreflex gain. Therefore, we conclude that hysteresis is not solely determined by barosensory vessel behaviour but by the complex interaction of mechanical and neural aspects of the arterial baroreflex.

Static and dynamic changes in carotid artery diameter in humans during and after strenuous exercise

Arterial baroreflex function is altered by dynamic exercise, but it is not clear to what extent baroreflex changes are due to altered transduction of pressure into deformation of the barosensory vessel wall. In this study we measured changes in mean common carotid artery diameter and the pulsatile pressure: diameter ratio (PDR) during and after dynamic exercise. Ten young, healthy subjects performed a graded exercise protocol to exhaustion on a bicycle ergometer. Carotid dimensions were measured with an ultrasound wall‐tracking system; central arterial pressure was measured with the use of radial tonometry and the generalized transfer function; baroreflex sensitivity (BRS) was assessed in the post‐exercise period by spectral analysis and the sequence method. Data are given as means ±s.e.m. Mean carotid artery diameter increased during exercise as compared with control levels, but carotid distension amplitude did not change. PDR was reduced from 27.3 ± 2.7 to 13.7 ± 1.0 μm mmHg−1. Immediately after stopping exercise, the carotid artery constricted and PDR remained reduced. At 60 min post‐exercise, the carotid artery dilated and the PDR increased above control levels (33.9 ± 1.4 μm mmHg−1). The post‐exercise changes in PDR were closely paralleled by those in BRS (0.74 ≤r≤ 0.83, P < 0.05). These changes in mean carotid diameter and PDR suggest that the mean baroreceptor activity level increases during exercise, with reduced dynamic sensitivity; at the end of exercise baroreceptors are suddenly unloaded, then at 1 h post‐exercise, baroreceptor activity increases again with increasing dynamic sensitivity. The close correlation between PDR and BRS observed at post‐exercise underlies the significance of mechanical factors in arterial baroreflex control.

Opposite changes in carotid versus aortic stiffness during healthy human pregnancy.

Systemic arterial compliance has been known to increase during healthy pregnancy, whereas, recently, the carotid artery has been reported to stiffen. To clarify this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and carotid artery elastic parameters in a cohort of pregnant women. Twelve normotensive pregnant women were studied longitudinally during the three trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP (postpartum). Carotid artery diastolic diameter and pulsatile distension was measured by an echo-wall tracking method and carotid pulse pressure by applanation tonometry. Carotid strain, compliance, distensibility coefficient, stiffness index beta, Einc (incremental elastic modulus) and augmentation index were calculated. Aortic PWV was determined to estimate aortic distensibility. All carotid artery elastic parameters indicated significant stiffening from T1 to T3 (1.8+/-0.2 versus 2.9+/-0.3 mmHg for Einc), which was reversed after delivery (2.3+/-0.2 mmHg). Aortic PWV decreased during pregnancy (6.2+/-0.2 versus 5.4+/-0.2 m/s) and increased in the PP period (6.7+/-0.2 m/s). No correlation was found between changes in carotid artery elastic parameters and changes in aortic PWV either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally specific stiffening during pregnancy, which appears to represent a qualitatively different change in arterial elastic behaviour.

Transposition of Great Arteries Is Associated With Increased Carotid Artery Stiffness

Transposition of great arteries is the consequence of abnormal aorticopulmonary septation. Animal embryonic data indicate that septation and elastogenesis are related events, but human and clinical data are not available. We tested the hypothesis that large artery elastic function was impaired in patients with transposition of great arteries. We studied 34 patients aged 9 to 19 years, 12±3 years after atrial switch operation; 14 patients aged 7 to 9 years, 8±1 years after arterial switch operation; and 108 healthy control subjects matched for age. Carotid artery diastolic diameter and pulsatile distension were determined by echo wall-tracking; carotid blood pressure was measured by tonometry. Systolic pressure was higher and diastolic pressure was lower in patients than in controls. Patients with atrial and arterial switch repair were compared with their respective controls by 2-factor ANOVA. For patients with atrial switch repair versus control, stiffness index &bgr; was 4.9±1.5 versus 3.1±1.0 (P<0.001); for patients witch arterial switch versus control, stiffness index &bgr; was 3.8±1.1 versus 2.1±0.6 (P<0.001). Similar differences were observed for carotid compliance, distensibility, and incremental elastic modulus as well. The interaction term was not significant for any of the elastic variables, indicating that carotid stiffening was a characteristic of the condition and not the consequence of different hemodynamics. Carotid artery is markedly stiffer in patients, suggesting that impaired elastogenesis may constitute part of the congenital abnormality. Since carotid artery stiffness has been established as an independent cardiovascular risk factor, this condition may have consequences in the clinical management of these patients.

Comparison of aortic arch and carotid sinus distensibility in humans—relation to baroreflex sensitivity

We compared aortic arch (AA) and carotid sinus (CS) distensibility, and determined the relationship between baroreflex sensitivity (BRS) and distensibility coefficients of AA and CS (DCAA and DCCS, respectively). In 47 healthy 19-71-year-old subjects, AA and CS end-diastolic diameter (D) and pulsatile distension (delta D) was measured with ultrasound and arterial pressure by sphygmomanometer and Finapres. DC was calculated as 2delta D/(D x delta P), where delta P is the pulse pressure. BRS was determined by the sequence method. Data are given as mean +/- S.D.; significance was set at p < 0.05. DCAA and DCCS were linearly related across subjects (r = 0.80, p < 0.001). No difference between DCAA and DCCS (3.8 +/- 1.4 x 10(-3) and 4.2 + 2.2 x 10(-3) mm Hg(-1), respectively) was found for all subjects (paired t-test). However, at ages < 35 years, DCCS exceeded DCAA, whereas this relation was reversed at ages > 35 years. Age accounted for 53% of variability in DCAA and 73% of variability in DCCS. BRS was related to DC (linear regression), with the BRS-DCAA relation being steeper and closer (r = 0.73, p < 0.001) than the BRS-DCCS relation (r = 0.54, p < 0.05). It is suggested that aortic baroreceptors may have a dominant role in heart rate control.

Measurement of aortic arch distension wave with the echo-track technique.

The aim of this study was to use the echo-track method for measuring aortic arch diameter, distension waveform and elastic parameters. Data were obtained from 50 healthy volunteers of 32 +/- 15 y (mean +/- 1 SD). The aortic arch was interrogated from the suprasternal position with M-mode ultrasonography using a 3.5-MHz transducer; diameter and distension waves were determined by means of an echo-track algorithm (WTS, Pie Medical); arterial blood pressure was measured in the arm with sphygmomanometry. Aortic arch diameter, distension, distensibility and compliance were 24.55 +/- 2.99 mm, 2199 +/- 726 micrometer, 3.9 +/- 1.4. 10(-3) mmHg(-1) and 1.86 +/- 0.61 mm(2). mmHg(-1), respectively. Intrasession, interobserver and intersession variability was less than 10%, 10% and 18%, respectively. It is concluded that aortic arch distension wave can be recorded noninvasively with acceptable reproducibility, allowing assessment of aortic elastic parameters, and yielding insight into pressure wave reflection within the arterial system.

The Method of Distance Measurement and Torso Length Influences the Relationship of Pulse Wave Velocity to Cardiovascular Mortality

BACKGROUND The method of estimating distance traveled by the pulse wave, used in the calculation of pulse wave velocity (PWV), is not standardized. Our objective was to assess whether different methods of distance measurement influenced the association of PWV to cardiovascular mortality in hemodialysis (HD) patients. METHODS Ninety-eight chronic HD patients had their PWV measured using three methods for distance estimation; PWV1: suprasternal notch-to-femoral site minus suprasternal notch-to-carotid site, PWV2: carotid-to-femoral site, PWV3: carotid-to-femoral site minus suprasternal notch-to-carotid site. Carotid-to-femoral distance was used to approximate torso length. Patients were followed for a median of 30 months and the association of PWV and cardiovascular mortality was assessed using survival analysis before and after stratification for torso length. RESULTS The three methods resulted in significantly different PWV values. During follow-up 50 patients died, 32 of cardiovascular causes. In log-rank tests, only tertiles of PWV1 was significantly related to outcome (P values 0.017, 0.257, 0.137, for PWV1, PWV2, and PWV3, respectively). In adjusted Cox, proportional hazards regression only PWV1 was related to cardiovascular mortality. In stratified analysis, however, among patients with below median torso length all PWV values were related to outcome, whereas in patients with above median torso length none of the PWV methods resulted in significant relationship to outcome. CONCLUSIONS PWV calculated using suprasternal notch-to-femoral distance minus suprasternal notch-to-carotid distance provides the strongest relationship to cardiovascular mortality. Longer torso weakens the predictive value of PWV, possibly due to more tortuosity of the aorta hence, more error introduced when using surface tape measurements.

The effect of low-dose carvedilol, nebivolol, and metoprolol on central arterial pressure and its determinants: a randomized clinical trial.

In this prospective, open‐label, randomized, controlled clinical trial the effects of low‐dose carvedilol, nebivolol, and metoprolol on central arterial pressure and augmentation index (AIx) and its heart rate–corrected value (AIx@75) were assessed. The authors randomized 75 hypertensive patients (18–70 years) to carvedilol 12.5/25 mg, metoprolol 50/100 mg, or nebivolol 2.5/5 mg daily and followed them up for 3 months. Central arterial pressure and AIx were measured with applanation tonometry at baseline and at the end of follow‐up. Analyses were restricted to 60 completers. Central systolic pressure decreased equally in all 3 treatment arms. AIx remained unchanged, while AIx@75 decreased significantly by 5.4%±2.5% in the nebivolol group. According to general linear models, individual change in heart rate was a strong predictor of change in AIx in the carvedilol group (r2=0.23, P=.03) although no similar association was found in the nebivolol group (r2=0.09). The impact of β‐blockers with vasodilator effects on pressure augmentation seems to be different with nebivolol having the largest potential of decreasing AIx@75. While AIx changes associated with carvedilol treatment are strongly driven by heart rate changes, those associated with nebivolol treatment seem to be the result of other mechanisms.