Pieter F. F. Wijn

Baroreceptor reflex sensitivity in human neonates: the effect of postmenstrual age

We performed a cross‐sectional study in human infants to determine if indices of R–R interval variability, systolic blood pressure (SBP) variability, and baroreceptor reflex sensitivity change with postmenstrual age (PMA: gestational age + postnatal age). The electrocardiogram, arterial SBP and respiration were recorded in clinically stable infants (PMA, 28–42 weeks) in the quiet sleep state in the first days after birth. (Cross‐)spectral analyses of R–R interval series and SBP series were performed to calculate the power of low‐frequency (LF, indicating baroreceptor reflex activity, 0.04–0.15 Hz) and high‐frequency (HF, indicating parasympathetic activity, individualized between the p‐10 and p‐90 values of respiratory frequency) fluctuations, and transfer function phase and gain. The mean R–R interval, and LF and HF spectral powers of R–R interval series increased with PMA. The mean SBP increased with PMA, but not the LF and HF spectral powers of SBP series. In the LF range, cross‐spectral analysis showed high coherence values (> 0.5) with a consistent negative phase shift between R–R interval and SBP, indicating a ∼3 s lag in R–R interval changes in relation to SBP. Baroreceptor reflex sensitivity, calculated from LF transfer gain, increased significantly with PMA, from 5 (preterm) to 15 ms mmHg−1 (term). Baroreceptor reflex sensitivity correlated significantly with the (LF and) HF spectral powers of R–R interval series, but not with the LF and HF spectral powers of SBP series. The principal conclusions are that baroreceptor reflex sensitivity and spectral power in R–R interval series increase in parallel with PMA, suggesting a progressive vagal maturation with PMA.

Cardiovascular fluctuations and transfer function analysis in stable preterm infants.

To examine the baroreceptor reflex function, a beat-to-beat analysis between systolic blood pressure (SBP) and R-R interval fluctuations was studied in 10 stable appropriate-for-gestational age preterm infants (range, 27.2–33.7 wk) in the first postnatal week during quiet sleep. Spectral power analysis, using fast Fourier transform, and transfer functions (gain and phase difference) between SBP and R-R fluctuations were estimated in a low-frequency band (LF, 0.03–0.2 Hz) and high-frequency band (HF defined as the frequency band between the 10th and 90th centiles of the individual respiratory frequency). The LF/HF ratio reflects the sympathovagal balance. The mean frequency (±SD) of LF peaks was centered at 0.07 ± 0.02 Hz. The mean frequency (±SD) of the individual HF band was 0.82 ± 0.21 Hz. The LF/HF ratio in the R-R interval series [median, 29; interquartile range (IQR), 16–40] was higher than in the SBP series (median, 8; IQR, 4–14). The gain between R-R interval and SBP fluctuations (median, 4.2 ms/mm Hg; IQR, 2.4–5.0) in the LF band was higher than in the HF band (median, 1.7 ms/mm Hg; IQR, 1.4–3.0). SBP fluctuations lead R-R interval fluctuations in the LF band with a median phase difference of +96° (IQR, 67–132). At LF the fluctuations in SBP precede changes in R-R interval with a time delay of 3.8 s. These observations indicate a dominant role of the sympathetic system in stable preterm infants in comparison with published adult values. Cross-spectral analysis allows a test for tracking the development of the sympathetic system in neonates.

Evaluation of two methods for continuous cardiac output assessment during exercise in chronic heart failure patients.

The purpose of this study was to evaluate the accuracy of two techniques for the continuous assessment of cardiac output in patients with chronic heart failure (CHF): a radial artery pulse contour analysis method that uses an indicator dilution method for calibration (LiDCO) and an impedance cardiography technique (Physioflow), using the Fick method as a reference. Ten male CHF patients (New York Heart Association class II-III) were included. At rest, cardiac output values obtained by LiDCO and Physioflow were compared with those of the direct Fick method. During exercise, the continuous Fick method was used as a reference. Exercise, performed on a cycle ergometer in upright position, consisted of two constant-load tests at 30% and 80% of the ventilatory threshold and a symptom-limited maximal test. Both at rest and during exercise LiDCO showed good agreement with reference values [bias +/- limits of agreement (LOA), -1% +/- 28% and 2% +/- 28%, respectively]. In contrast, Physioflow overestimated reference values both at rest and during exercise (bias +/- LOA, 48% +/- 60% and 48% +/- 52%, respectively). Exercise-related within-patient changes of cardiac output, expressed as a percent change, showed for both techniques clinically acceptable agreement with reference values (bias +/- LOA: 2% +/- 26% for LiDCO, and -2% +/- 36% for Physioflow, respectively). In conclusion, although the limits of agreement with the Fick method are pretty broad, LiDCO provides accurate measurements of cardiac output during rest and exercise in CHF patients. Although Physioflow overestimates cardiac output, this method may still be useful to estimate relative changes during exercise.

Beat-to-beat detection of fetal heart rate: Doppler ultrasound cardiotocography compared to direct ECG cardiotocography in time and frequency domain.

In order to obtain power spectral information on the fetal heart rate in stages of pregnancy earlier than labor an algorithm has been developed to calculate the fetal heart rate on a beat-to-beat basis from Doppler ultrasound cardiotocographic signals. The algorithm was evaluated by comparing the calculated fetal heart rate with the heart rate determined from direct ECG signals measured with a scalp electrode. Heart rates were compared both in time and frequency domain. In the time domain the results achieved by both methods correlate well (correlation coefficient = 0.977 (p < 0.001)), in the frequency domain the results correlate even better (correlation coefficient = 0.991 (p < 0.001)). Based on these findings, it can be concluded that the developed algorithm provides a valuable tool for obtaining power spectral information on the fetal heart rate in stages of pregnancy earlier than labor.

Sports-related flow limitations in the iliac arteries in endurance athletes: aetiology, diagnosis, treatment and future developments.

Approximately one in five top-level cyclists will develop sports-related flow limitations in the iliac arteries. These flow limitations may be caused by a vascular lumen narrowing due to endofibrotic thickening of the intima and/or by kinking of the vessels. In some athletes, extreme vessel length contributes to this kinking. Endofibrotic thickening is a result of a repetitive vessel damage due to haemodynamic and mechanical stress. Atherosclerotic intimal thickening is seldom encountered in these young athletes. This type of sports-related flow limitation shows no relationship with the classical risk factors for atherosclerosis like smoking, hypercholesterolaemia or family predisposition for arterial diseases.The patient’s history is paramount for diagnosis. If an athlete reports typical claudication-like complaints in a leg at maximal effort, which disappear quickly at rest, approximately two out of three will have a flow limitation in the iliac artery. In current (sports) medical practice, this diagnosis is often missed, since a vascular cause is not expected in this healthy athletic population. Even if suspected, the routinely available diagnostic tests often appear insufficient. Definite diagnosis can be made by a combination of the patient’s history and special designed tests consisting of a maximal cycle ergometer test with ankle blood pressure measurements and/or an echo-Doppler examination with provocative manoeuvres like hip flexion and exercise.Conservative treatment consists of diminishing or even completely stopping the provocative sports activity. If conservative treatment is insufficient or deemed unacceptable, surgical treatment might be considered. As surgery needs to be tailored to the underlying lesions, a detailed analysis before surgery is necessary. Standard clinical tests, used for visualising atherosclerotic diseases, are inadequate to identify and quantify the causes of flow limitations. Echo-Doppler examination and magnetic resonance angiography with both flexed and extended hips have been proven to be adequate tools. In particular, overprojection and eccentric location of the lesions seriously limit the usefulness of a two-dimensional technique like digital subtraction angiography.In the early stages, when kinking has not yet led to intimal thickening or excessive lengthening, simple surgical release of the iliac artery is effective. However, for patients with excessive vessel lengths or extensive endofibrotic thickening, a vascular reconstruction may be necessary. A major drawback of these interventions is that long-term effects and complications are unknown.As both the diagnostic methods and the treatments for this type of flow limitation differ substantially from routine vascular procedures, these patients should be examined in specialised research centres with appropriate diagnostic tools and medical experience.

Noninvasive Assessment of Blood Pressure Variability in Preterm Infants

The feasibility of measuring blood pressure (BP) variability by a noninvasive beat-to-beat finger arterial BP device (Finapres) was assessed in preterm infants. By application of the finger cuff around the infants wrist, time and frequency domain (spectral power) analysis of noninvasive beat-to-beat BP signals were compared with intra-arterial measurements. A fast Fourier Transform was used to compute the spectral power density from 128-s periods. The low-frequency band (LF; 0.04–0.15 Hz) is partly associated with baroreflex activity. The high-frequency band (HF; 0.4–1.5 Hz) is associated with respiratory activity. In eight subjects above 1000 g, reliable signals could be obtained. We observed a high correlation between noninvasive and intra-arterial beat-to-beat systolic BP values (mean r value ± SD, 0.87 ± 0.11), with a gain close to 1 (mean gain ± SD, 1.0 ± 0.4 mm Hg/mm Hg). Finapres estimated beat-to-beat systolic BP changes more accurately than diastolic values. We found a very high amount of linear coupling, expressed as coherence function, between the power spectra of noninvasive and intra-arterial systolic BP measurements. For systolic BP, the (pooled) group mean ± SEM coherence values were 0.93 ± 0.00 and 0.91 ± 0.01 for LF and HF fluctuations, respectively (NS). The wrist method of Finapres in neonates has limited value in estimating absolute BP but is useful in a clinical research situation, where identification of beat-to-beat changes in systolic BP is more important. Finapres provides a noninvasive tool for investigating autonomic cardiovascular regulation (baroreflex sensitivity, spectral analysis of BP fluctuations) in neonates.

Automatic burst detection for the EEG of the preterm infant

To aid with prognosis and stratification of clinical treatment for preterm infants, a method for automated detection of bursts, interburst-intervals (IBIs) and continuous patterns in the electroencephalogram (EEG) is developed. Results are evaluated for preterm infants with normal neurological follow-up at 2 years. The detection algorithm (MATLAB®) for burst, IBI and continuous pattern is based on selection by amplitude, time span, number of channels and numbers of active electrodes. Annotations of two neurophysiologists were used to determine threshold values. The training set consisted of EEG recordings of four preterm infants with postmenstrual age (PMA, gestational age + postnatal age) of 29-34 weeks. Optimal threshold values were based on overall highest sensitivity. For evaluation, both observers verified detections in an independent dataset of four EEG recordings with comparable PMA. Algorithm performance was assessed by calculation of sensitivity and positive predictive value. The results of algorithm evaluation are as follows: sensitivity values of 90% ± 6%, 80% ± 9% and 97% ± 5% for burst, IBI and continuous patterns, respectively. Corresponding positive predictive values were 88% ± 8%, 96% ± 3% and 85% ± 15%, respectively. In conclusion, the algorithm showed high sensitivity and positive predictive values for bursts, IBIs and continuous patterns in preterm EEG. Computer-assisted analysis of EEG may allow objective and reproducible analysis for clinical treatment.

Are oxygen uptake kinetics in chronic heart failure limited by oxygen delivery or oxygen utilization

BACKGROUND The delay in O(2) uptake kinetics during and after submaximal physical activity (O(2) onset and recovery kinetics, respectively) correlates well with the functional capacity of patients with chronic heart failure (CHF). This study examined the physiological background of this delay in moderately impaired CHF patients by comparing kinetics of cardiac output (Q) and O(2) uptake (V(O(2))). METHODS Fourteen stable CHF patients (New York Heart Association class II-III) and 8 healthy subjects, matched for age and body mass index, were included. All subjects performed a submaximal constant-load exercise test to assess O(2) uptake kinetics. Furthermore, in 10 CHF patients Q was measured by a radial artery pulse contour analysis method, which enabled the simultaneous modelling of exercise-related kinetics of Q and V(O(2)). RESULTS Both O(2) onset and recovery kinetics were delayed in the patient group. There were no significant differences between the time constants of Q and V(O(2)) during exercise-onset (62+/-25 s versus 59+/-28 s, p=0.51) or recovery (61+/-25 s versus 57+/-20 s, p=0.38) in the patient group, indicating that O(2) delivery was not in excess of the metabolic demands in these patients. CONCLUSION The delay in O(2) onset and recovery kinetics in moderately impaired CHF patients is suggested to be due to limitations in O(2) delivery. Therefore, strategies aimed at improving exercise performance of these patients should focus more on improvements of O(2) delivery than on O(2) utilization.

Compartment Pressure Curves Predict Surgical Outcome in Chronic Deep Posterior Compartment Syndrome

Background: Results of surgery for chronic exertional compartment syndrome (CECS) of the lower leg deep posterior compartment are inferior compared with other types of CECS. Factors predicting success after surgery are unknown. Purpose: To study the prognostic value of preoperative compartmental pressure curves in patients receiving surgery for deep posterior compartment CECS. Study Design: Case series; Level of evidence, 4. Methods: Intracompartmental pressures (ICPs) of patients with deep posterior lower leg CECS were obtained at 4 time points (ie, before, immediately after, and 1 and 5 minutes after a standard exercise challenge test). Area under the 4-point pressure curve was calculated. Patients received a questionnaire investigating residual symptoms after surgery. Results: A complete data set was available for 52 patients (men, n = 23; age, 33 ± 14 years). They rated their 3-month postoperative clinical outcome as excellent (14%), good (38%), fair (35%), or poor (13%). Outcome at 3 months was related to the area under the preoperative 4-point pressure curve (excellent, 127 ± 28; good, 113 ± 25; fair, 100 ± 22; and poor, 88 ± 15; P = .005; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.08). At the long-term follow-up (39 ± 24 months), all 5 cardinal symptoms (pain, tight feeling, cramps, weakness, and diminished sensibility) were greatly attenuated (P < .001) in the successfully operated group. Long-term success was 48%. Delay in diagnosis was related to poor outcome (P = .04). Correlations between pressures/area under the 4-point pressure curve and long-term outcome were not significant, however. Conclusion: Preoperative measured intracompartmental pressures obtained in rest and after a standard exercise test may predict success of surgery for deep posterior compartment CECS of the lower limb. Further standardizing of preoperative pressure protocols may confirm that compartmental pressure analysis has diagnostic as well as predictive properties.

Cardiovascular autonomic regulation in preterm infants: the effect of atropine.

To study cardiovascular autonomic control, we assessed the effect of atropine on heart rate (HR) and blood pressure (BP) variability in 12 preterm infants (range 26–32 wk) before intubation for respiratory insufficiency. Spectral power analysis of R-R interval and systolic BP (SBP) series were estimated in a low-frequency (LF; 0.04–0.15 Hz) and high-frequency (HF; 0.4–1.5 Hz) band and evaluated for a 10-min period before and a 10-min period after atropine sulfate (0.01 mg/kg). Baroreceptor reflex (BR) functioning was estimated using transfer function analysis at LF (coherence, gain, and phase). Atropine resulted in a significant 12% increase in steady-state HR (p < 0.01) and unchanged SBP. For R-R interval series, the total spectral power decreased 6-fold (p < 0.01), which was predominantly due to a reduction in the LF band (16-fold; p < 0.01). In contrast, we observed a significant increase (25%; p < 0.05) in total spectral power of SBP series partly as a result of an increase in HF power. The LF power of SBP series was not altered. The median LF transfer gain (BR sensitivity) between SBP and R-R interval decreased from 4.2 to 1.4 ms/mm Hg (p < 0.01) after atropine. The LF phase relationship (BP leads R-R interval fluctuations by ∼4 s) was not changed after atropine. In conclusion, even in preterm infants in distress, atropine modulates HR and BP variability, suggesting that BR-mediated parasympathetic control of heart rate is of significance for cardiovascular control at that age.