Arlette Girard

Short-term blood pressure and heart rate variability in congenital central hypoventilation syndrome (Ondine's curse)

The effect of CCHS (congenital central hypoventilation syndrome, or Ondines curse) on short-term BP (blood pressure) and HR (heart rate) variability was evaluated in 16-year-old subjects presenting a form of CCHS requiring night ventilatory assistance. The 12 patients were compared with 12 age- and gender-matched healthy volunteers. Recordings were obtained during daytime while the subjects were breathing spontaneously. Continuous BP was measured with a Finapres device in the supine, head-up tilt and standing positions. The manoeuvre of actively standing was also analysed. HR levels were elevated in CCHS subjects at supine rest (+23%) with a reduced HR overall variability (-88%). The low- and high-frequency components of HR variability were affected. BP levels were preserved at rest, but the manoeuvres demonstrated a limited capacity to elevate BP. There was no overshoot in BP during the manoeuvre of actively standing, and steady standing BP levels in patients were not higher than supine BP levels as usually observed in healthy controls. The spontaneous baroreflex sensitivity estimated using the sequence technique or the cross-spectral analysis fell in the patients to approx. one-third of the sensitivity estimated in the healthy controls whatever the position. This cardiovascular profile suggests a predominant vagal dysfunction with signs of vagal withdrawal and baroreflex failure, and relative preservation of the cardiac and vascular sympathetic function. It is likely that the impaired ontogeny of the visceral reflexes, considered now to cause CCHS syndrome, includes the baroreceptive pathway and mainly its vagal component.

Effects of drugs on the autonomic control of short-term heart rate variability.

The autonomic nervous system links the brain and the heart. Efferent links in the neural control of the heart consist of sympathetic and parasympathetic (vagal) fibers innervating the sinus node. Because sympathetic and vagal firing alter spontaneous sinus node depolarization, cardiac rate and rhythm convey information about autonomic influences on the heart. The easy availability of ECG rendered possible the assessment of sinus rhythm as an index of autonomic outflow. The frequency-domain approach uses non-invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function. Spectral profiles resulting from vagal or sympathetic blockades at the cardiac (or vascular) level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients (microneurographic recordings, norepinephrine spillover). This review also reports some pitfalls encountered in variability studies.

Elastin mutation is associated with a reduced gain of the baroreceptor – heart rate reflex in patients with Williams syndrome

Abstract Microdeletion of chromosome 7q, encompassing the elastin locus, has been identified in patients with Williams syndrome (WS). This study tested the hypothesis that loss of medial elastin affects the discharge of baroreceptors and consequently the baroreflex sensitivity (BRS). Eight untreated patients with WS (14.8 ± 2.4 y, m ± SEM) were compared to 8 healthy subjects (15.1 ± 2.3 y). Blood pressure (BP) was recorded using a Finapres® monitor in the supine position. Systolic BP (SBP) levels were 117.8 ± 4.4 mmHg in WS compared to 110.9 ± 5.7 in controls (ns). Pulse rate (PR, taken as a surrogate for heart rate) was higher in the WS (89.6 ± 1.0 vs 74.1 ± 2.3 beats/min in controls, P < 0.01). The variance (total power) of PI variability was reduced in WS subjects. The amplitudes of the low frequency (LF, 0.1 Hz) and high frequency (HF, respiratory) PI component (modulus) were reduced in WS (210.5 ± 4.3 vs 34.6 ± 2.6 ms, P = 0.02 for LF, 13.1 ± 2.5 vs 39.3 ± 8.5 ms, P = 0.01 for HF). The gain of the SBP-PI transfer function was diminished in the low frequency (LF, 0.1 Hz) and the HF range as well (5.8 ± 0.7 vs 12.1 ± 1.8 ms/mmHg for LF, P < 0.01 and 6.2 ± 1.0 vs 21.7 ± 4.6 ms/mmHg for HF, P < 0.01). The BRS obtained with the sequence technique was also reduced in WS (8.2 ± 0.9 vs 21.5 ± 2.9 ms/mmHg in controls, P < 0.001). The percent of beats involved in baroreflex sequences observed in WS was also diminished to 20 % compared to 48 % in controls (P < 0.001). In conclusion a BRS reduction associated with a PR elevation was observed in normotensive WS subjects. It is likely abnormal elastic fiber assembly at the arterial level alters baroreceptor discharges.

Acute effects of bisoprolol on respiratory sinus arrhythmia.

Summary— Respiratory sinus arrhythmia (RSA) is often quantified by computing the spectra of heart period (HP) or of its reciprocal heart rate (HR) at the respiratory frequency. This study was undertaken to describe the effect of an acute beta‐blockade achieved with bisoprolol on RSA, obtained during a calibrated breathing (breathing frequency 0.25 Hz, tidal volume VT 500 or 700 mL) in 15 normal volunteers, using a double‐blind, placebo‐controlled, cross‐over method. The two heart signals were computed and the RSA values were compared to the individual estimates of vagal tone obtained using an additional atropine injection. The difference between the HP (or HR) value obtained after beta‐blockade and the HP (or HR) value observed following the double blockade (bisoprolol plus atropine) was taken as an index of cardiac vagal tone. Bisoprolol administration resulted in a significant reduction in HR reaching 60.3 ± 1.4 bpm at VT of 500 mL (compared to 70.5 ± 1.8 bpm with placebo, P < 0.001). Changes in HP were also significant with an increase in HP reaching 1004.5 ± 22.2 msec at this controlled VT (compared to 860.3 ± 21.5 msec with placebo, P < 0.001). Similar changes were observed at a VT of 700 mL. The relationship between RSA in bpm and vagal tone was not significant for HR while a significant positive relationship was observed between RSA in msec and vagal tone for the two respiratory patterns (r = 0.65 for a tidal volume of 500 mL, P < 0.01, and r = 0.62 for 700 mL, P < 0.05). This demonstrates that the detection of the variability effect highly depends upon the unit. The parallelism between vagal tone and RSA supports the view that the HF component of HRV in msec quantifies the vagal tone. The increased RSA during beta‐blockade could well reflect this vagotonic effect of this class of drugs.

Effect of antihypertensive therapy on short-term blood pressure variability

Para Ile I C ro s s-o ve r Introduction Blood pressure (BP) and heart rate (HR) variability studies offer a functional approach to the assessment of the effects of drugs. The frequency domain approach uses non invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function [I]. Spectral profiles resulting from vagal or sympathetic blockades at the vascular or cardiac level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients. Sample size table The first practical question to solve, in order to design a clinical trial, is the sample size table derived from a repeatability study [2]. Such tables show that a cross-over design minimizes the required sample size. Table 1 illustrates this issue: the number of subjects to be included in a study in order to detect a 20% variation in the standing 0.1 Hz (midfrequency, MF) component of systolic BP (SBP) variability, with a power of 0.80, is reduced from 42 for a parallel design to 15 with a crossover design [3].