John M. Karemaker

Comparing Spectra of a Series of Point Events Particularly for Heart Rate Variability Data

Different methods for spectral analysis of the heart rate signal¿considered as series of point events¿are used in studies on heart rate variability. This paper compares these methods, focusing on the two principal ones: the interval spectrum, i.e., the spectrum of the interval series, and the spectrum of counts, which is related to the representation of the event series as a series of spikes (delta functions). Both autospectra are estimated for experimental heart rate data and are shown to produce similar results. This similarity is proven analytically, and it is shown that for small variations in interval length, the ratio of these spectra is PI(f)/PC(f) = [sin(¿f¿)/(¿f¿)]2, with PI and PC the interval spectrum and the spectrum of counts, respectively, f the frequency, and ¿the mean interval length. It is concluded that both autospectra are equivalent for the considered heart rate data, but that, when relating the heart rate signal to other signals (e.g., respiration, blood pressure) by means of cross spectra, the technique to be used depends on the characteristics of the second signal.

Relationships between short-term blood-pressure fluctuations and heart-rate variability in resting subjects I: a spectral analysis approach

A method to attribute the short-term variability of blood pressure and heart rate of resting subjects to their various causes, using spectral techniques, is presented. Power spectra and cross-spectra are calculated for beat-to-beat values of R-R interval and blood pressure from subjects who were seated in a comfortable chair. Interval values as well as systolic, mean and pulse pressures show variations linked to respiration and to the so-called 10 s rhythm. The diastolic pressure values are scarcely influenced by respiration in the normal respiratory range (0·20–0·35 Hz), but do show 10 s variability. Relationships between pressure and interval variability which indicate that the 10 s variability in systolic pressure leads the interval variation by two to three beats become manifest in cross-spectra; however, no such lag is found between the respiration-linked variations in systolic pressure and intervals. It is argued that the technique presented provides a critical test for models of the fast regulation of the cardiovascular system.

Human cerebral venous outflow pathway depends on posture and central venous pressure

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat‐to‐beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position, but mainly through the vertebral plexus in the upright position. A Valsalva manoeuvre while standing completely re‐opened the jugular veins. Results of ultrasound imaging of the right internal jugular vein cross‐sectional area at the level of the laryngeal prominence in six healthy subjects, before and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross‐sectional area (R2= 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway. The internal jugular veins are collapsed in the standing position and blood is shunted to an alternative venous pathway, but a marked increase in CVP while standing completely re‐opens the jugular veins.

Quantification of Wave Reflection in the Human Aorta From Pressure Alone: A Proof of Principle

Wave reflections affect the proximal aortic pressure and flow waves and play a role in systolic hypertension. A measure of wave reflection, receiving much attention, is the augmentation index (AI), the ratio of the secondary rise in pressure and pulse pressure. AI can be limiting, because it depends not only on the magnitude of wave reflection but also on wave shapes and timing of incident and reflected waves. More accurate measures are obtainable after separation of pressure in its forward (Pf) and reflected (Pb) components. However, this calculation requires measurement of aortic flow. We explore the possibility of replacing the unknown flow by a triangular wave, with duration equal to ejection time, and peak flow at the inflection point of pressure (FtIP) and, for a second analysis, at 30% of ejection time (Ft30). Wave form analysis gave forward and backward pressure waves. Reflection magnitude (RM) and reflection index (RI) were defined as RM=Pb/Pf and RI=Pb/(Pf+Pb), respectively. Healthy subjects, including interventions such as exercise and Valsalva maneuvers, and patients with ischemic heart disease and failure were analyzed. RMs and RIs using FtIP and Ft30 were compared with those using measured flow (Fm). Pressure and flow were recorded with high fidelity pressure and velocity sensors. Relations are: RMtIP=0.82RMmf+0.06 (R2=0.79; n=24), RMt30=0.79RMmf+0.08 (R2=0.85; n=29) and RItIP=0.89RImf+0.02 (R2=0.81; n=24), RIt30=0.83RImf+0.05 (R2=0.88; n=29). We suggest that wave reflection can be derived from uncalibrated aortic pressure alone, even when no clear inflection point is distinguishable and AI cannot be obtained. Epidemiological studies should establish its clinical value.

Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

Background—In patients with a malignant hypertension, immediate parenteral treatment with blood pressure–lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. Methods and Results—In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA Vmean to MAP phase lead and static CA as the MCA Vmean to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA Vmean to MAP phase lead was lower (30±8° versus 58±5°, mean±SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA Vmean decrease was 22±4%, along with a 27±3% reduction in MAP (from 166±4 to 121±6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82±0.15% cm · s−1 · % mm Hg−1; r=0.70±0.07). Conclusions—In patients with malignant hypertension, dynamic CA is impaired. An MCA Vmean plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA Vmean decreases almost one on one with MAP.

Time delays in the human baroreceptor reflex.

In 11 normotensive subjects with coronary artery disease, low intensity electrical stimulation of the carotid sinus nerves (CSN) was triggered by the R-wave in the electrocardiogram with an adjustable delay. The latent period was estimated between the start of CSN stimulation and the onset of the reflex-PP-interval prolongation and, during right atrial pacing, the onset of the reflex fall of diastolic arterial pressure and prolongation of the AV-interval. The latency to the reverse changes was determined after switching CSN stimulation off. The PP-interval changes started after a latency of 0.5-0.6 s. This latency was independent of the respiratory phase and it was independent of the directional change of the afferent activity. AV-interval changes started after about 1 s. When heart rate was fixed, arterial pressure changes started after 2-3 s. It is estimated that central processing of baroreceptor afferent activity may require 0.25 s in the human.

Denervation of Carotid Baro‐ and Chemoreceptors in Humans

Experimental denervation in animals has shown that carotid baro‐ and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro‐ and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short‐ and long‐term effects of carotid baro‐ and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short‐term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.

Effects of aging on blood pressure variability in resting conditions.

The objective of this study was to determine the effect of aging on beat-to-beat blood pressure and pulse interval variability in resting conditions and to determine the effect of aging on the sympathetic and vagal influence on the cardiovascular system by power spectral analysis of blood pressure and pulse interval. We studied three groups of healthy, normotensive subjects: young (10 to 15 years, n = 16), adult (20 to 40 years, n = 16), and elderly (70 to 90 years, n = 25). Beat-to-beat blood pressure was measured by Finapres during 20 minutes supine and 10 minutes standing. Overall systolic and diastolic blood pressures and pulse interval variability were determined as SD and as coefficient of variation. Also, relative powers of the mid-frequency (0.08 to 0.12 Hz) and high-frequency bands (0.15 to 0.40 Hz) were determined by spectral analysis. In these subjects no differences in blood pressure variability (either as SD or coefficient of variation) were found between age groups, except for the coefficient of variation of standing diastolic blood pressure, which decreased with aging. Pulse interval variability decreased with aging. Power of the mid-frequency band of systolic and diastolic blood pressures was markedly decreased in the elderly, especially in the standing position. Power of the high-frequency band of pulse interval was also decreased in the elderly. Baroreflex sensitivity calculated by fast Fourier transformation spectral analysis was decreased in the elderly subjects compared with the younger groups. In conclusion, we found no change in the overall variability of blood pressure with aging. Mid-frequency spectral power of blood pressure and mid- and high-frequency spectral powers of pulse interval variability were decreased in the elderly. These results suggest that aging does not merely influence the magnitude of blood pressure and pulse interval variability but causes a complex rearrangement of the variability pattern by changes in neurocardiovascular regulation.

Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction.

Abstract.The aim of this study was to investigate in patients with neurogenic orthostatic hypotension the mechanism and usefulness of abdominal compression to increase standing blood pressure. In three protocols, 23 patients underwent abdominal compression. Protocol 1 evaluated in a 40–60° head-up-tilt position, the effect of abdominal compression on caval vein and femoral diameter, arterial blood pressure and hemodynamics. Protocol 2 documented the relationship between the level of compression and the arterial pressure response. Protocol 3 investigated the ability to maintain standing blood pressure by an elastic binder. During head-up-tilt, compression (40 mm Hg) resulted in a reduction in diameter of the caval vein (mean –2.6mm, range –1.4 to 0.6), without a change in femoral vein diameter. Stroke volume increased by 14 % (range –1 to 23) and blood pressure (systolic/diastolic) by 30/14 mmHg (range 7/2 to 69/36), both p < 0.05; 40 mmHg compression was associated with a higher pressure response than 20 mmHg (mean 18/8 mmHg, range 6/2 to 43/20 vs. mean 9/4 mmHg, range –1/0 to 18/8, p < 0.05). Elastic abdominal binding increased standing blood pressure with 15/6mmHg (range –3/3 to 36/14, p < 0.05). We conclude that in patients with neurogenic orthostatic hypotension, abdominal compression increases standing blood pressure to a varying degree by increasing stroke volume.

Last word on point:counterpoint: respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism

Blood pressure and heart periods fluctuate at respiratory frequencies in healthy humans. Some researchers ([8][1], [23][2]) explain this as a cause-and-effect relation: blood pressure changes trigger baroreflex-mediated R-R interval changes. Here I make the case that respiratory sinus arrhythmia is