Zsuzsanna Lénárd

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.

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.

Static versus dynamic distensibility of the carotid artery in humans

In clinical studies, the elastic behavior of central arteries is usually assessed by measuring dynamic distensibility. In this study, we aimed to investigate how dynamic and static distensibility of the common carotid artery (D_dyn and D_stat, respectively) are related in 28 healthy volunteers of 20–71 years. The carotid diameter and its change with the pressure pulse were measured using an ultrasound echo-tracking device. Arterial blood pressure was measured by Finapres and carotid pressure was determined by applanation tonometry. D_dyn was determined at rest using the pressure pulse, while D_stat was determined during pressor responses induced by handgrip or cold pressor test. Data are given as mean ± 1 SD. In younger subjects (<35 years), D_stat did not differ from D_dyn (7.0 ± 3.4 vs. 6.5 ± 2.1·10^–3·mm Hg^–1, respectively), whereas in older subjects (>35 years), D_stat was significantly higher than D_dyn (3.8 ± 1.4 vs. 2.1 ± 0.9· 10^–3·mm Hg^–1, p < 0.001). For all subjects, D_stat and D_dyn decreased with increasing age and mean arterial pressure (MAP). Using stepwise multiple regression analysis, the strongest predictor of D_stat proved to be MAP, while that of D_dyn was age. D_stat was found to be linearly related to the hysteresis loop area of the pressure-diameter relation (r = 0.94), i.e. to vessel wall viscosity. It is concluded that, with increasing age, static distensibility overestimates the distension capacity of large arteries.

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.

Cardiovagal autonomic function in sedentary and trained offspring of hypertensive parents

In young normotensive subjects, parental hypertension is associated with stiffening of the carotid artery and reduction in cardiovagal outflow and baroreflex gain. In subjects without parental hypertension regular exercise training was found to attenuate age‐related reduction in carotid compliance and baroreflex gain. The aim of the present study was to test the hypothesis that regular physical activity is associated with better parameters of carotid artery elasticity, increased cardiovagal outflow and higher baroreflex gain in normotensive offspring of hypertensive parents. We studied 98 healthy, sedentary or endurance exercise trained subjects (49 men, 18–27 years of age) with or without family history of hypertension (FH+ and FH−, respectively) in a cross‐sectional design. In the sedentary group spontaneous baroreflex indices (sequence method and spectral techniques) were lower in FH+ subjects than in their FH− peers, while in trained subjects these indices were not different between FH+ and FH−. Furthermore, in the FH+ group trained subjects had higher baroreflex indices than their sedentary peers, while in the FH− group no significant differences were found. Carotid compliance and distensibility coefficient (echo‐tracking ultrasound and applanation tonometry) were not different in FH− sedentary and trained subjects, but were higher in FH+ trained subjects as compared to their sedentary peers. Significant but modest relationships were found between spontaneous baroreflex indices and carotid artery elastic parameters across all subjects. Our present data indicate that in subjects with parental hypertension aerobic exercise training is associated with higher levels of cardiovagal outflow and baroreflex gain, which finding, however, is not explained by greater elasticity of the carotid artery.

Carotid artery stiffening does not explain baroreflex impairment in pre-eclampsia

Stiffening of the barosensory vessel wall in hypertension has been suggested to play a role in the associated baroreflex impairment. The carotid distensibility-BRS (baroreflex sensitivity) relationship, however, has not been studied in pre-eclampsia, a condition where hypertension is spontaneously reversible. Twelve normotensive pregnant women and 12 patients with pre-eclampsia matched for maternal age and week of gestation were studied in the third trimester and 3 months postpartum. Carotid artery diastolic diameter and pulsatile distension was measured by echo-wall tracking and carotid pulse pressure by applanation tonometry, and the carotid distensibility coefficient was calculated. Spontaneous BRS was determined by the sequence and spectral methods from 10 min continuous recording of ECG and finger arterial blood pressure. In the third trimester, carotid distensibility was lower in patients with pre-eclampsia than in normotensive pregnant women (2.47+/-0.17 compared with 4.08+/-0.16 x 10(-3)/mmHg); postpartum, it increased moderately in patients, but remained below normotensive values (3.25+/-0.12 compared with 4.25+/-0.19 x 10(-3)/mmHg). In the third trimester, both patients and healthy pregnant women had equally low BRS values; postpartum, the various BRS indices increased markedly (by 60-190%) and to the same level in both groups. No correlation was found between changes in carotid artery distensibility and those in BRS from the third trimester to postpartum period in patients and healthy pregnant women. The lack of association between changes in carotid distensibility and BRS suggest that stiffening of the carotid artery in pre-eclampsia is not responsible for baroreflex dysfunction.

Effect of vitamin E on carotid artery elasticity and baroreflex gain in young, healthy adults

In this study we tested the hypothesis that dietary vitamin E supplementation can improve carotid artery elasticity and cardio-vagal baroreflex gain in young, healthy individuals. A total of 20 subjects were studied in a double-blind, placebo-controlled, randomized study. Subjects in the active treatment group received 700 IU/day vitamin E for 1 month. Each subject was studied three times: before, during and 1 month after treatment. Plasma vitamin E levels were determined using high-performance liquid chromatography. Carotid artery diameter was measured by ultrasound and radial artery pressure by tonometry. Baroreflex function was assessed by time and frequency domain spontaneous indices. Plasma vitamin E levels increased by 123%, which was associated with a 20% increase in carotid artery compliance and a 30-60% increase in baroreflex indices. All these changes regressed 1 month after cessation of vitamin E supplementation. Significant correlations were observed across conditions (control, treatment and recovery), among plasma vitamin E concentrations, carotid artery compliance and distensibility values and two of the baroreflex gain indices in the treatment group. Our results demonstrate that vitamin E supplementation can increase carotid artery compliance and baroreflex gain in young, apparently healthy adults.