Johannes J. van Lieshout

Non-invasive pulsatile arterial pressure and stroke volume changes from the human finger.

In this paper we review recent developments in the methodology of non‐invasive finger arterial pressure measurement and the information about arterial flow that can be obtained from it. Continuous measurement of finger pressure based on the volume‐clamp method was introduced in the early 1980s both for research purposes and for clinical medicine. Finger pressure tracks intra‐arterial pressure but the pressure waves may differ systematically both in shape and magnitude. Such bias can, at least partly, be circumvented by reconstruction of brachial pressure from finger pressure by using a general inverse anti‐resonance model correcting for the difference in pressure waveforms and an individual forearm cuff calibration. The Modelflow method as implemented in the Finometer computes an aortic flow waveform from peripheral arterial pressure by simulating a non‐linear three‐element model of the aortic input impedance. The methodology tracks fast changes in stroke volume (SV) during various experimental protocols including postural stress and exercise. If absolute values are required, calibration against a gold standard is needed. Otherwise, Modelflow‐measured SV is expressed as change from control with the same precision in tracking. Beat‐to‐beat information on arterial flow offers important and clinically relevant information on the circulation beyond what can be detected by arterial pressure.

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78% ± 4%; mean ± s.d.) was halfway between the arterial (98% ± 1%) and jugular venous oxygenation (SVO2; 61% ± 6%). Both NIRS devices monitored SCap (P < 0.001) within ~5% as SvO2 increased from 39% ± 5% to 79% ± 7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29 ± 8 to 65 ± 15 cm/sec. When SCap fell below ~70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P < 0.001) and brain lactate release increased concomitantly (P < 0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r > 0.74; P < 0.05). These results show that NIRS is an adequate cerebral capillaryoxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.

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.

Nexfin noninvasive continuous blood pressure validated against Riva-Rocci/Korotkoff.

BACKGROUND The Finapres methodology offers continuous measurement of blood pressure (BP) in a noninvasive manner. The latest development using this methodology is the Nexfin monitor. The present study evaluated the accuracy of Nexfin noninvasive arterial pressure (NAP) compared with auscultatory BP measurements (Riva-Rocci/Korotkoff, RRK). METHODS In supine subjects NAP was compared to RRK, performed by two observers using an electronic stethoscope with double earpieces. Per subject, three NAP-RRK differences were determined for systolic and diastolic BP, and bias and precision of differences were expressed as median (25th, 75th percentiles). Within-subject precision was defined as the (25th, 75th percentiles) after removing the average individual difference. RESULTS A total of 312 data sets of NAP and RRK for systolic and diastolic BP from 104 subjects (aged 18-95 years, 54 males) were compared. RRK systolic BP was 129 (115, 150), and diastolic BP was 80 (72, 89), NAP-RRK differences were 5.4 (-1.7, 11.0) mm Hg and -2.5 (-7.6, 2.3) mm Hg for systolic and diastolic BP, respectively; within-subject precisions were (-2.2, 2.3) and (-1.6, 1.5) mm Hg, respectively. CONCLUSION Nexfin provides accurate measurement of BP with good within-subject precision when compared to RRK.

Noninvasive continuous arterial blood pressure monitoring with Nexfin

Background: If invasive measurement of arterial blood pressure is not warranted, finger cuff technology can provide continuous and noninvasive monitoring. Finger and radial artery pressures differ; Nexfin® (BMEYE, Amsterdam, The Netherlands) measures finger arterial pressure and uses physiologic reconstruction methodologies to obtain values comparable to invasive pressures. Methods: Intra-arterial pressure (IAP) and noninvasive Nexfin arterial pressure (NAP) were measured in cardiothoracic surgery patients, because invasive pressures are available. NAP-IAP differences were analyzed during 30 min. Tracking was quantified by within-subject precision (SD of individual NAP-IAP differences) and correlation coefficients. The ranges of pressure change were quantified by within-subject variability (SD of individual averages of NAP and IAP). Accuracy and precision were expressed as group average ± SD of the differences and considered acceptable when smaller than 5 ± 8 mmHg, the Association for the Advancement of Medical Instrumentation criteria. Results: NAP and IAP were obtained in 50 (34–83 yr, 40 men) patients. For systolic, diastolic, mean arterial, and pulse pressure, median (25–75 percentiles) correlation coefficients were 0.96 (0.91–0.98), 0.93 (0.87–0.96), 0.96 (0.90–0.97), and 0.94 (0.85–0.98), respectively. Within-subject precisions were 4 ± 2, 3 ± 1, 3 ± 2, and 3 ± 2 mmHg, and within-subject variations 13 ± 6, 6 ± 3, 9 ± 4, and 7 ± 4 mmHg, indicating precision over a wide range of pressures. Group average ± SD of the NAP-IAP differences were −1 ± 7, 3 ± 6, 2 ± 6, and −3 ± 4 mmHg, meeting criteria. Differences were not related to mean arterial pressure or heart rate. Conclusion: Arterial blood pressure can be measured noninvasively and continuously using physiologic pressure reconstruction. Changes in pressure can be followed and values are comparable to invasive monitoring.

Lactate fuels the human brain during exercise

The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O2 uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O2/(glucose+½ lactate)] from a resting value of 6 to <2. The CMR also decreases when plasma lactate is not increased, as during prolonged exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined β1‐ and β2‐adrenergic receptor blockade but not with β1‐adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a β2‐adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood‐brain barrier. The pattern of CMR decrease under various forms of brain activation suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions.—Quistorff, B., Secher, N. H., and Van Lieshout, J. J. Lactate fuels the human brain during exercise. FASEB J. 22, 3443–3449 (2008)

Muscle Tensing During Standing: Effects on Cerebral Tissue Oxygenation and Cerebral Artery Blood Velocity

Background and Purpose— When standing up causes dizziness, tensing of the leg muscles may alleviate the symptoms. We tested the hypothesis that leg tensing improves orthostatic tolerance via enhanced cerebral perfusion and oxygenation. Methods— In 10 healthy young adults, the effects of leg tensing on transcranial Doppler–determined middle cerebral artery (MCA) mean blood velocity (Vmean) and the near-infrared spectroscopy–determined frontal oxygenation (O2Hb) were assessed together with central circulatory variables and an arterial pressure low-frequency (LF) (0.07 to 0.15 Hz) domain evaluation of sympathetic activity. Results— Standing up reduced central venous pressure by (mean±SEM) 4.3±2.6 mm Hg, stroke volume by 49±7 mL, cardiac output by 1.9±0.4 L/min, and mean arterial pressure at MCA level by 9±4 mm Hg, whereas it increased heart rate by 30±4 beats per minute (P <0.05). MCA Vmean declined from 67±4 to 56±3 cm/s, O2Hb decreased by 7±2.8%, and LF spectral power increased (P <0.05). Leg tensing increased central venous pressure by 1.4±2.7 mm Hg and cardiac output by 1.8±0.4 L/min with no significant effect on blood pressure, whereas heart rate decreased by 11±3 beats per minute (P <0.05). MCA Vmean increased to 63±3 cm/s and O2Hb increased by 2.1±2.6%, whereas LF power declined (P <0.05). Within 2 minutes after leg tensing, these effects had disappeared. Conclusions— During standing, tensing of the leg muscles attenuates a reduction in cerebral perfusion and oxygenation as it stabilizes central circulatory variables and reduces sympathetic activity.

Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Point: Sympathetic activity does influence cerebral blood flow

Cerebral arteries are abundantly innervated by sympathetic fibers, but their influence on cerebral vessels was held unimportant for almost a century ([2][1], [20][2]). Whether there is sympathetic influence on cerebral blood flow (CBF) is important in the management of hypotensive patients. If there

Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure

Treatment with head-up tilt sleeping and low-dose fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic blood pressure in patients with neurogenic orthostatic hypotension. The aim of the present study was to examine whether the improvement in orthostatic blood pressure during combined treatment with low-dose fludrocortisone and nocturnal head-up tilt in patients with neurogenic orthostatic hypotension can be attributed to expansion of plasma volume or to increased total peripheral resistance. The effects of a 3-week treatment with fludrocortisone and nocturnal head-up tilting on the postural changes in arterial pressure, heart rate, and cardiac output (pulse contour) were evaluated in eight consecutive patients with orthostatic hypotension. The period during which the patients were able to remain in the standing position without orthostatic complaints increased minimally from 3 to 10 minutes. The decrease in arterial pressure after 1 minute of standing—(means with standard deviations in parentheses) systolic, 49 (20) mm Hg; diastolic, 18 (11) mm Hg—before treatment was produced by a greater than normal decrease in cardiac output: 37% (10%) in patients with neurogenic orthostatic hypotension versus-14% (8%) in control subjects. Treatment increased upright arterial pressure from 83 (19) mm Hg systolic and 55 (13) mm Hg diastolic to 114 (22) mm Hg systolic and 60 (16) mm Hg diastolic by limiting the decrease in cardiac output. Body weight increased but hematocrit did not change. Leg pressure-volume relationship decreased in the two patients studied. The responses of plasma renin activity and aldosterone to orthostatic stress prior to treatment were subnormal and became even lower after treatment. The improvement in upright blood pressure in orthostatic hypotension during treatment with fludrocortisone and nocturnal head-up sleeping is the result of a reduction in the orthostatic decrease in cardiac output. Preliminary data suggest that the expanded body fluid volume is allocated to the perivascular space rather than to the intravascular space.Treatment with head-up tilt sleeping and low-dose fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic blood pressure in patients with neurogenic orthostatic hypotension. The aim of the present study was to examine whether the improvement in orthostatic blood pressure during combined treatment with low-dose fludrocortisone and nocturnal head-up tilt in patients with neurogenic orthostatic hypotension can be attributed to expansion of plasma volume or to increased total peripheral resistance.The effects of a 3-week treatment with fludrocortisone and nocturnal head-up tilting on the postural changes in arterial pressure, heart rate, and cardiac output (pulse contour) were evaluated in eight consecutive patients with orthostatic hypotension.The period during which the patients were able to remain in the standing position without orthostatic complaints increased minimally from 3 to 10 minutes. The decrease in arterial pressure after 1 minute of standing—(means with standard deviations in parentheses) systolic, 49 (20) mm Hg; diastolic, 18 (11) mm Hg—before treatment was produced by a greater than normal decrease in cardiac output: 37% (10%) in patients with neurogenic orthostatic hypotension versus-14% (8%) in control subjects. Treatment increased upright arterial pressure from 83 (19) mm Hg systolic and 55 (13) mm Hg diastolic to 114 (22) mm Hg systolic and 60 (16) mm Hg diastolic by limiting the decrease in cardiac output. Body weight increased but hematocrit did not change. Leg pressure-volume relationship decreased in the two patients studied. The responses of plasma renin activity and aldosterone to orthostatic stress prior to treatment were subnormal and became even lower after treatment.The improvement in upright blood pressure in orthostatic hypotension during treatment with fludrocortisone and nocturnal head-up sleeping is the result of a reduction in the orthostatic decrease in cardiac output. Preliminary data suggest that the expanded body fluid volume is allocated to the perivascular space rather than to the intravascular space.

Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI

In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.