J. J. Van Lieshout

Continuous stroke volume monitoring by modelling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress

The relationship between aortic flow and pressure is described by a three-element model of the arterial input impedance, including continuous correction for variations in the diameter and the compliance of the aorta (Modelflow). We computed the aortic flow from arterial pressure by this model, and evaluated whether, under orthostatic stress, flow may be derived from both an invasive and a non-invasive determination of arterial pressure. In 10 young adults, Modelflow stroke volume (MFSV) was computed from both intra-brachial arterial pressure (IAP) and non-invasive finger pressure (FINAP) measurements. For comparison, a computer-controlled series of four thermodilution estimates (thermodilution-determined stroke volume; TDSV) were averaged for the following positions: supine, standing, head-down tilt at 20 degrees (HDT20) and head-up tilt at 30 degrees and 70 degrees (HUT30 and HUT70 respectively). Data from one subject were discarded due to malfunctioning thermodilution injections. A total of 155 recordings from 160 series were available for comparison. The supine TDSV of 113+/-13 ml (mean+/-S.D.) dropped by 40% to 68+/-14 ml during standing, by 24% to 86+/-12 ml during HUT30, and by 51% to 55+/-15 ml during HUT70. During HDT20, TDSV was 114+/-13 ml. MFSV for IAP underestimated TDSV during HDT20 (-6+/-6 ml; P<0.05), but that for FINAP did not (-4+/-7 ml; not significant). For HUT70 and standing, MFSV for IAP overestimated TDSV by 11+/-10 ml (HUT70; P<0.01) and 12+/-9 ml (standing; P<0.01). However, the offset of MFSV for FINAP was not significant for either HUT70 (3+/-8 ml) or standing (3+/-9 ml). In conclusion, due to orthostasis, changes in the aortic transmural pressure may lead to an offset in MFSV from IAP. However, Modelflow correctly calculated aortic flow from non-invasively determined finger pressure during orthostasis.

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.

Pulse contour cardiac output derived from non-invasive arterial pressure in cardiovascular disease

Pulse contour methods determine cardiac output semi‐invasively using standard arterial access. This study assessed whether cardiac output can be determined non‐invasively by replacing the intra‐arterial pressure input with a non‐invasive finger arterial pressure input in two methods, Nexfin CO‐trek® and Modelflow®, in 25 awake patients after coronary artery bypass surgery. Pulmonary artery thermodilution cardiac output served as a reference. In the supine position, the mean (SD) differences between thermodilution cardiac output and Nexfin CO‐trek were 0.22 (0.77) and 0.44 (0.81) l.min−1, for intra‐arterial and non‐invasive pressures, respectively. For Modelflow, these differences were 0.70 (1.08) and 1.80 (1.59) l.min−1, respectively. Similarly, in the sitting position, differences between thermodilution cardiac output and Nexfin CO‐trek were 0.16 (0.78) and 0.34 (0.83), for intra‐arterial and non‐invasive arterial pressure, respectively. For Modelflow, these differences were 0.58 (1.11) and 1.52 (1.54) l.min−1, respectively. Thus, Nexfin CO‐trek readings were not different from thermodilution cardiac output, for both invasive and non‐invasive inputs. However, Modelflow readings differed greatly from thermodilution when using non‐invasive arterial pressure input.

Physical manoeuvres for combating orthostatic dizziness in autonomic failure

Some patients with orthostatic hypotension combat orthostatic dizziness by leg-crossing and squatting. Changes in blood pressure with these manoeuvres were studied in 7 patients with hypoadrenergic orthostatic hypotension and in 6 healthy subjects. Without leg-crossing, 5 of the patients reported dizziness within 10 min of standing up. Crossing of the legs allowed all to stand for 10 min or more, and there was an associated increase in mean blood pressure of 13 (SD 6) mm Hg compared with 1 (4) in healthy controls; the corresponding figures for squatting were 44 (18) and 8 (6) mm Hg. Patients with orthostatic intolerance should be told about these blood-pressure-raising manoeuvres.

Physical manoeuvres that reduce postural hypotension in autonomic failure.

Guest LectureA Young female with autonomic failure is described. She successfully reduced the symptoms of orthostatic hypotension by application of physical manoeuvres like leg-crossing, bending forward and placing a foot on a chair. The beneficial effects of these manoeuvres can be explained by a small (10–15 mmHg) increase in mean arterial pressure to a level just sufficient to maintain adequate cerebral blood flow. The underlying common mechanism appears to be an increase of thoracic blood volume by translocation of blood from the vascular beds below the diaphragm to the chest. Instruction in these physical manoeuvres should be part of the management programme to reduce the disabilities arising from postural hypotension in patients with autonomic failure.

Orthostatic Tolerance, Cerebral Oxygenation, and Blood Velocity in Humans With Sympathetic Failure

BACKGROUND AND PURPOSE Patients with orthostatic hypotension due to sympathetic failure become symptomatic when standing, although their capability to maintain cerebral blood flow is reported to be preserved. We tested the hypothesis that in patients with sympathetic failure, orthostatic symptoms reflect reduced cerebral perfusion with insufficient oxygen supply. METHODS This study addressed the relationship between orthostatic tolerance, mean cerebral artery blood velocity (V(mean), determined by transcranial Doppler ultrasonography), oxygenation (oxyhemoglobin [O(2)Hb], determined by near-infrared spectroscopy), and mean arterial pressure at brain level (MAP(MCA), determined by finger arterial pressure monitoring [Finapres]) in 9 patients (aged 37 to 70 years; 4 women) and their age- and sex-matched controls during 5 minutes of standing. RESULTS Supine MAP(MCA) (108+/-14 versus 86+/-14 mm Hg) and V(mean) (84+/-21 versus 62+/-13 cm. s(-1)) were higher in the patients. After 5 minutes of standing, MAP(MCA) was lower in the patients (31+/-14 versus 72+/-14 mm Hg), as was V(mean) (51+/-8 versus 59+/-9 cm. s(-1)), with a larger reduction in O(2)Hb (-11. 6+/-4 versus -6.7+/-4.5 micromol. L(-1)). Four patients terminated standing after 1 to 3.5 minutes. In these symptomatic patients, the orthostatic fall in V(mean) was greater (45+/-6 versus 64+/-10 cm. s(-1)), and the orthostatic decrease in O(2)Hb (-12.0+/-3.3 versus -7.6+/-3.9 micromol. L(-1)) tended to be larger. The reduction in MAP(MCA) was larger after 10 seconds of standing, and MAP(MCA) was lower after 1 minute (25+/-8 versus 40+/-6 mm Hg). CONCLUSIONS In patients with sympathetic failure, the orthostatic reduction in cerebral blood velocity and oxygenation is larger. Patients who become symptomatic within 5 minutes of standing are characterized by a pronounced orthostatic fall in blood pressure, cerebral blood velocity, and oxygenation manifest within the first 10 seconds of standing.

Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone

We studied the effect of sleeping in the head‐up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150–200 mmol Na+ d−1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P < 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from −64/‐42/‐25 ± 29/21/17mmHg to −53/‐37/‐23 ± 31/24/20 mmHg (P < 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from −63/ −40/ −24 ± 20/12/11 mmHg to −21/‐19/‐8 ± 12/10/5 mmHg (P < 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 ± 9/8/7 mmHg initially to 95/69/57 ± 27/22/20 mmHg during combined treatment (P < 0.05 for systolic and mean BP), and remained unchanged during the 14‐month (range 8–70 month) follow‐up period. Nocturnal sodium excretion decreased from 8.0 ± 2.3 mmol h−1 to 5.9 ± 1.9 mmol h−1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5‐2.4 kg) (P < 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo‐adrenergic orthostatic hypotension.

Stroke volume of the heart and thoracic fluid content during head-up and head-down tilt in humans

Background:  The stroke volume (SV) of the heart depends on the diastolic volume but, for the intact organism, central pressures are applied widely to express the filling of the heart.

Circulatory response evoked by a 3 s bout of dynamic leg exercise in humans.

1. The mechanisms underlying the pronounced transient fall in arterial blood pressure evoked by a 3 s bout of bicycle exercise were investigated in twenty healthy young adults and four patients with hypoadrenergic orthostatic hypotension. 2. In healthy subjects a 3 s bout of upright cycling induced a 28 +/‐ 3 mmHg fall in mean arterial pressure at 12 s. The fall in mean arterial pressure was preceded by a 12 +/‐ 2 mmHg rise in right atrial pressure at 3 s and accompanied by a 54 +/‐ 7% increase in left ventricle stroke volume at 6 s. Systemic vascular resistance dropped 48 +/‐ 2% at 7 s after the start of the manoeuvre to remain at that level for approximately 5 s. The total response lasted about 20 s. During sustained upright cycling the initial fall in mean arterial pressure was also present, but less pronounced (17 +/‐ 2 vs. 26 +/‐ 3 mmHg). A 3 s bout of supine cycling in four patients with hypoadrenergic orthostatic hypotension also elicited a pronounced fall in mean arterial pressure (22 +/‐ 4 mmHg) and in systemic vascular resistance (38 +/‐ 4%). 3. A bout of exercise with a large muscle mass induces two main effects. First, it mechanically increases filling of the heart due to activation of the muscle pump, resulting in an increase in cardiac output. Second, it induces a drop in systemic vascular resistance. The increase in cardiac output is not sufficient to compensate fully for the pronounced fall in systemic vascular resistance and the result is a transient fall in arterial pressure at the onset of whole‐body exercise. The rise in right atrial pressure evoked by 3 s cycling is abrupt and large, but the almost immediate onset and rapid fall of the systemic vascular resistance is too fast for sympathetically mediated reflex effects due to stimulation of the cardiopulmonary afferents. An important factor involved in the drop in systemic vascular resistance appears to be local, non‐autonomically mediated vasodilatation in exercising muscles, since it also occurs in patients with autonomic failure.

Estimation of beat-to-beat changes in stroke volume from arterial pressure: A comparison of two pressure wave analysis techniques during head- up tilt testing in young, healthy men

ObjectiveThe aim of this study was to compare beat-to-beat changes in stroke volume (SV) estimated by two different pressure wave analysis techniques during orthostatic stress testing: pulse contour analysis and Modelflow,ie, simulation of a three-element model of aortic input impedance.MethodsA reduction in SV was introduced in eight healthy young men (mean age, 25; range, 19–32 y) by a 30-minute head-up tilt maneuver. Intrabrachial and noninvasive finger pressure were monitored simultaneously. Beat-to-beat changes in SV were estimated from intrabrachial pressure by pulse contour analysis and Modelflow. In addition, the relative differences in Modelflow SV obtained from intrabrachial pressure and noninvasive finger pressure were assessed.ResultsBeat-to-beat changes in Modelflow SV from intrabrachial pressure were comparable with pluse contour measures. The relative difference between the two methods amounted to 0.1±1% (mean±SEM) and was not dependent on the duration of tilt. The diference between Modelflow apoplied to intrabrachial pressure and finger pressure amounted to −2.7±1.3% (p=0.04). This difference was not dependent on the duration of tilt or level of arterial pressure.ConclusionsBased on different mathematical models of the human arterial system, pulse contour and Modelflow compute similar changes in SV from intrabrachial pressure during orthostatic stress testing in young healthy men. The magnitude of the differnece in SV derived from intrabrachial and finger pressure may vary among subjects; Modelflow SV from noninvasive finger pressure tracks fast and brisk changes in SV derived from intrabrachial pressure.