Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure.

In the present study, we have assessed in patients with neurogenic orthostatic hypotension the haemodynamics underlying the reduced tolerance to standing after prolonged recumbency at night. In 10 patients with neurogenic orthostatic hypotension (age 33-68 years), of which seven were being treated with fludrocortisone and/or sleeping in the 12 degrees head-up tilt position, 24 h continuous non-invasive finger blood pressure was recorded by a Portapres device. Beat-to-beat blood pressure, heart rate, stroke volume, cardiac output and total peripheral vascular resistance obtained by pulse contour analysis were assessed during 5 min of standing in the evening (at 22.30 hours) and in the morning (at 06.30 hours). On average, the inverse of the normal 24 h blood pressure profile was found, with a large diversity in blood pressure profiles among patients. Supine blood pressure values were similar, but standing blood pressure values were lower in the morning than in the evening (P<0.01). This resulted from larger falls in stroke volume and cardiac output upon standing in the morning compared with the evening, while total peripheral resistance did not change. There was no relationship between the decrease in body weight during the night (mean 0.9 kg; range 0.2-1.6 kg) and the evening-morning difference in standing blood pressure. We conclude that, in patients with neurogenic orthostatic hypotension, the impaired tolerance to standing in the morning is due to larger falls in stroke volume and cardiac output. Not only nocturnal polyuria, but also a redistribution of body fluid, are likely mechanisms underlying the pronounced decreases in stroke volume and cardiac output after prolonged recumbency at night.

The compliance of the porcine pulmonary artery depends on pressure and heart rate.

1. The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo-static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross-sectional area (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood flow can be computed from the Ppa using a windkessel model. We investigated whether Cps can be interchanged with Cd. 2. In nine anaesthetized pigs, we determined the mean CSA and Cd of the pulmonary artery at various Ppa levels, ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of measurements were carried out, one series at a spontaneously changing heart rate (n = 9) and one series at a constant heart rate (n = 6). To determine CSA a conductance method was used. 3. Cps depended on pressure. The mean CSA versus mean Ppa curves were sigmoid and steepest in the series with the increasing heart rate (established by bleeding). The CSA versus Ppa loop during a heart cycle, giving Cd, was approximately linear and almost closed. The Cd versus mean Ppa relationship was bell shaped. Its width was smaller if the heart rate increased during the series of measurements. The pressure, where Cd was maximum, was higher at higher heart rates. Furthermore, the maximum Cd was not affected by the heart rate. 4. Because the pulmonary artery constricts with increasing heart rate, Cps will be overestimated during procedures where heart rate increases. Cd should be determined on a beat-to-beat basis to calculate flow because it changes with mean pulmonary arterial pressure and heart rate.

Estimation of blood pressure variability from 24-hour ambulatory finger blood pressure.

Portapres is a noninvasive, beat-to-beat finger blood pressure (BP) monitor that has been shown to accurately estimate 24-hour intra-arterial BP at normal and high BPs. However, no information is available on the ability of this device to accurately track ambulatory BP variability. In 20 ambulatory normotensive and hypertensive subjects, we measured 24-hour BP by Portapres and through a brachial artery catheter. BP and pulse interval variabilities were quantified by (1) the SDs of the mean values (overall variability) and (2) spectral power, computed either by fast Fourier transform and autoregressive modeling of segments of 120-second duration for spectral components from 0.025 to 0.50 Hz or in a very low frequency range (between 0.00003 and 0.01 Hz) by broadband spectral analysis. The 24-hour SD of systolic BP obtained from Portapres (24+/-2 mm Hg) was greater than that obtained intra-arterially (17+/-1 mm Hg, P<0.01), but the overestimation was less evident for diastolic (3+/-1 mm Hg, P<0.01) and mean (3+/-1 mm Hg, P<0.01) BP. The BP spectral power <0.15 Hz was also overestimated by Portapres more for systolic than for diastolic and mean BPs; similar findings were obtained by the fast Fourier transform, the autoregressive approach, and focusing on the broadband spectral analysis. BP spectral power >0.15 Hz obtained by the Portapres was similar during the day but lower during the night when compared with those obtained by intra-arterial recordings (P<0.01). No differences were observed between Portapres and intra-arterial recordings for any estimation of pulse interval variabilities. The overestimation of BP variability by Portapres remained constant over virtually the entire 24-hour recording period. Thus, although clinical studies are still needed to demonstrate the clinical relevance of finger BP variability, our study shows that Portapres can be used with little error to estimate 24-hour BP variabilities if diastolic and mean BPs are used. For systolic BP, the greater error can be minimized by using correction factors.

Why use Finapres or Portapres rather than intra-arterial or intermittent non-invasive techniques of blood pressure measurement?

In the clinic, blood pressure is measured almost exclusively using non-invasive intermittent techniques, of which the auscultatory (Riva-Rocci/Korotkoff, RRK) and the computerized oscillometric method are most often used. However, both methods only provide a momentary value. In addition, the accuracy is hampered by phenomena such as cuff response and white coat hypertension, thus providing artefactually increased values. The vascular unloading technique of Penáz together with the Physiocal criteria of Wesseling provide reliable, non-invasive and continuous estimates of blood pressure. This technique is thus an alternative to the invasive intra-arterial measurements in many cases, without the risks and ethical questions inherent to invasive measurements. Since the pressure waveform is available continuously, computations such as pulse contour and Modelflow cardiac output, spectral analysis and baroreflex sensitivity provide further information on the dynamics of the cardiovascular system on a beat-to-beat basis, similar to intra-arterial measurements.

Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt.

Head-down tilted bedrest is a ground-based microgravity simulation model. Since in this position the influence of chief external determinants of circadian blood pressure variation, i.e. activity and posture, are reduced, it may reveal endogenous oscillatory factors. The effects of 42 days of 6 degrees head-down tilt on the circadian profiles of continuous finger blood pressure, heart rate, stroke volume, cardiac output and total peripheral resistance were analysed. In seven healthy volunteers (25-31 years) twelve 22 h Portapres registrations were performed: two in an ambulatory baseline period, eight during 42 days of head-down tilt, and two during recovery. Stroke volume was estimated by a pulse contour method ('Modelflow') from the finger arterial blood pressure tracing. Head-down tilt rapidly reduced circadian BP variation, especially for diastolic blood pressure. No effect of long-term head-down tilt on blood pressure level was observed. The day-night difference in heart rate was essentially unaffected. Cardiac output was maintained through an increase of heart rate and simultaneous decline of stroke volume. Our observations confirm the overriding importance of physical activity and orthostatic load on the diurnal variation of BP. The time-frame of the changes in stroke volume and heart rate during head-down tilt might point to a contribution of other factors besides a reduction of circulating blood volume affecting cardiovascular performance under these conditions.

Elastic properties of human aortas in relation to age and atherosclerosis: a structural model.

A new structural model is described for the tension-radius relationship of blood vessels, taking into account their mechanically important constituents: collagen, elastin and smooth muscle. The model has four characteristic parameters: EC, the Young's modulus of the collagen fibres; ESE, the Young's modulus of the combined smooth-muscle/elastin network; epsilon mu, the amount of strain at which the high stiffness region on the tension-radius curve is reached, and eta an indicator for the degree of collagen fibre stretching. The structural stiffness of the wall constituents is reflected by EC and ESE whereas the global stiffness of the entire blood vessel is described by epsilon mu and eta. All these elasticity parameters are pressure independent, in contrast to generally quoted values for the incremental modulus or vascular compliance which are strongly pressure dependent. Hence, an objective comparison of the mechanical properties for various types of blood vessel, based on the present model parameters, has been made possible. The model was successfully fitted to tension-radius data of 65 human aortas, age range 30-88 years, with moderate or severe atherosclerosis. The structural as well as the global stiffness changes with age, e.g. collagen stiffness shows a ninefold increase over 60 years. Global stiffness depends on atherosclerosis.

Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording.

We tested Portapres, an innovative portable, battery-operated device for the continuous, noninvasive, 24-hour ambulatory measurement of blood pressure in the finger. Portapres is based on Finapres, a stationary device for the measurement of finger arterial pressure. Systems were added to record signals on tape, to alternate measurements between fingers automatically each 30 minutes, and to correct for the hydrostatic height of the hand. We compared the pressure as measured by Portapres with contralateral intrabrachial pressure measured with an Oxford device. Results were obtained in eight volunteers and 16 hypertensive patients. Time lost due to artifact was about 10% for each device. In two patients a full 24-hour Oxford profile was not obtained. In the remaining 22 subjects finger systolic, diastolic, and mean pressures differed +1 (SD 9), -8 (6), and -10 (6) mm Hg, respectively, from intrabrachial pressure. These diastolic and mean pressure underestimations are similar to what was found earlier for Finapres, are typical for the technique, and are systematic. Avoiding brisk hand movements resulted in fewer waveform artifacts. The hand had to be kept covered to continue recording at low outside temperatures. Sleep was not disturbed by Portapres, and arterial pressure showed a marked fall during siesta and nighttime. There were no major limitations in behavior, and no discomfort that originated from continuous monitoring was reported. Measurements continued normally during physical exercise. Portapres provides for the first time continuous 24-hour, noninvasive ambulatory blood pressure waveform monitoring and offers real and obvious advantages over current noninvasive and invasive devices.

Continuous finger arterial pressure: utility in the cardiovascular laboratory.

The clinical utility for autonomic research purposes of the Finapres, a device for measuring finger arterial pressure continuously and noninvasively, was assessed by estimating its accuracy, precision and within-subject variability in 48 subjects, aged 18-65 years, in comparison with intraarterial brachial blood pressure. At differences of -3.5 +/- 12, -8.0 +/- 8 and -4.4 +/- 8 mmHg from simultaneous intrabrachial systolic, mean and diastolic pressure, the Finapres meets the Association for the Advancement of Medical Instruments (AAMI) accuracy requirements for systolic and diastolic, but not for mean pressure. The precision requirements were nearly met for mean and diastolic, but not for systolic pressure. These results compare to those of others under widely varying circumstances in anaesthetized and awake subjects, and are comparable to those published for the auscultatory technique. The within-subject precision of Finapres is high; the 95% confidence intervals are 3.4-4.5 mmHg for systolic, 1.5-2.0 mmHg for mean and 1.7-2.2 mmHg for diastolic. This makes the Finapres suitable for tracking changes in blood pressure. Four case studies are provided as examples of the value of the Finapres in the clinical laboratory.

[Pressor effect of a soccer match (1988 European championship), registered via the Portapress]. / Pressor-effect van een voetbalwedstrijd (Europees Kampioenschap 1988), geregistreerd met de Portapres.

With the Portapres, continuous ambulatory non-invasive measurement of finger arterial blood pressure is possible. By means of this system blood pressure measurements were made in five healthy male subjects watching a match of the Dutch National team at home, during the 1988 European Championship. In two of them an evident pressor response was found.

Pressure-diameter relationships of segments of human finger arteries.

Pressure-diameter relationships of segments of human finger arteries, aged 57-85 years, were measured in vitro. The arteries, obtained at autopsy within 48 h after death, were stored in glucose-free Tyrode at 4 degrees C. Experiments began within 40 h after autopsy. The diameter responses to various transmural pressure changes, with and without the addition of noradrenaline to the Tyrode solution in the specimen chamber, were compared with the responses of freshly excised rat tail arteries. In general, pressure-diameter relations of human finger artery segments were similar to those of rat tail artery segments, with a steep slope in the collapse region near zero pressure. Also, spontaneous rhythmic contractions and myogenic activity induced by high transmural pressures were similar to those observed in the fresh rat tail arteries. Human finger arteries, however, could contract to complete closure both spontaneously and after addition of noradrenaline, while rat tail arteries did not. The diameter changes of the arterial segments during forced 1 Hz oscillations of 20-50 mm Hg (2.7-6.7 kPa) amplitude superimposed on a mean transmural pressure were substantially smaller than those during quasi-steady inflation-deflation ramps over the same pressure range, indicating the presence of a strong viscous wall component.

[The effect of aging and sclerosis on the viscoelastic properties of the human thoracic aorta]. / De invloed van veroudering en sclerose op de visco-elastische eigenschappen van de menselijke aorta thoracalis.

This paper describes some results of our research on the viscoelastic properties of the human aorta. Pressure-diameter relations of 45 thoracic aortas, aged 30 to 88 years, were measured. The complex static measurement results were described by a model (formula) with three parameters. The dynamic (viscous) measurement results needed four parameters in a different model. De model parameters were next related to the age and the degree of sclerosis of the aortic segments. The results can be summarized as follows: the static properties change strongly with age; aortic compliance decreases substantially with aging; the dynamic (viscous) properties of the aorta do not change with age; although the degree of sclerosis of the aorta increased with age, we could not demonstrate a significant difference in the viscoelastic properties of 'normal' and sclerotic aortas. An explanation for the latter phenomenon was found in the dilation of the aorta which accompanies the increase of the degree of sclerosis and which serves as a hemodynamic compensation.

The pressure dependent dynamic elasticity of 35 thoracic and 16 abdominal human aortas in vitro described by a five component model.

Segments of 35 thoracic and 16 abdominal human aortas, including nine pairs, aged 30-78 yr at autopsy, were perfused with 37 degrees C Tyrode's solution at in situ length. Diameter changes due to 20 mmHg pressure steps between 20 and 180 mmHg were measured to 1 micron accuracy at an equivalent noise level of 0.1 micron RMS, using balanced transducers. Aortic creep curves at each pressure level were described individually by a constant plus bi-exponential creep model characterized by two creep fractions (alpha 1 and alpha 2) and two time constants (tau 1 and tau 2). Creep fractions and time constants increased substantially with the pressure level, indicating a significant effect of pressure or distension on aortic viscoelasticity. At 110 mmHg the mean +/- 1 S.D. parameter values were: thoracic aorta: alpha 1 = 0.076 +/- 0.017, alpha 2 = 0.102 +/- 0.028, tau 1 = 0.73 +/- 0.29 s, tau 2 = 14.0 +/- 4.1 s; abdominal aorta: alpha 1 = 0.078 +/- 0.017, alpha 2 = 0.101 +/- 0.025, tau 1 = 0.61 +/- 0.12 s, tau 2 = 12.1 +/- 3.4 s. Nine paired comparisons at each pressure level showed that creep fractions and time constants of thoracic and abdominal segments were not significantly different (p = 0.05).

Oxygen uptake of frog skeletal muscle fibres following tetanic contractions at 18 degrees C.

Oxygen consumption following isometric tetanic contractions of single fibres and multifibre preparations of the tibialis anterior muscle of Rana temporaria was determined by continuous polarographic measurement of the PO2 in a 280 microliter glass chamber. Mixing of the fluid surrounding the muscle was achieved by an Archimedian screw. Force was measured via a stainless-steel wire leaving the chamber via a glass capillary. The characteristics of the oxygen-measuring system were assessed by injection of 1.6 microliter dye into the chamber and filming its subsequent distribution, and by injection of 1.6 microliter Ringer solution with a high (or low) oxygen content into the chamber and measuring the subsequent change of oxygen. It was found that a change in oxygen was measured after a true delay of 3 s and with an over-all time constant of 3.25 s following that delay. For seven single fibres the oxygen consumption following a 3 s tetanus was on average 2.46 mumol g-1; the average integrated value of the developed stress was 0.98 N mm-2 s. These two values were on average about 45% lower for the same tetani of multifibre preparations, but the average ratio of oxygen consumption to integrated stress was the same. Oxygen consumption was varied by changing tetanus duration. When the amount of oxygen consumed was plotted against stress integral a non-linear relationship was found because oxygen consumption increased less than the integrated stress value with longer tetani. Oxygen consumption did not start at the onset of contraction but about 10 s later. It then followed an exponential time course with an average time constant of 120 s. Delay and time constant were independent of the amount of oxygen consumed. The finding that oxygen consumption follows contraction after a delay of a few seconds confirms a similar conclusion drawn indirectly from studies on recovery heat by other investigators. A dependency of the time course of oxygen consumption on tetanus duration, as reported in the literature for frog muscle at 0 degree C, was not found.

The static elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and the parameters of a new model.

Segments of 45 human thoracic and 20 abdominal aortas, including 13 pairs, aged 30-88 yr at autopsy, were perfused with 37 degrees C Tyrode's solution at in-situ length. Diameter changes due to 20 mmHg pressure steps, between 20 and 180 mmHg, were measured to 1 micron accuracy with balanced transducers. Absolute diameter at 100 mmHg was measured to 50 micron accuracy. At 100 mmHg, cross-sectional area ranged from 2.6 to 7.6 for thoracic and from 1.0 to 3.2 cm2 for abdominal segments. Compliances ranged from 1.9 to 17 for thoracic and from 0.6 to 4.4 mm3/mmHg.cm for abdominal segments. An arctangent model with three free parameters A(p) = Am(1/2 + tan-1 [p-p0)/p1)/pi) explained over 99% of the variance in area with pressure for each aorta. Changes in compliance, characteristic impedance and propagation velocity are equally well described. Abdominal fits on the average appeared down scaled by a factor of 2 and shifted 20 mmHg towards lower pressures from paired thoracic (significant at p = 0.001).