Yu-Sok Kim

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.

Dynamic cerebral autoregulatory capacity is affected early in Type 2 diabetes

Type 2 diabetes is associated with an increased risk of endothelial dysfunction and microvascular complications with impaired autoregulation of tissue perfusion. Both microvascular disease and cardiovascular autonomic neuropathy may affect cerebral autoregulation. In the present study, we tested the hypothesis that, in the absence of cardiovascular autonomic neuropathy, cerebral autoregulation is impaired in subjects with DM+ (Type 2 diabetes with microvascular complications) but intact in subjects with DM- (Type 2 diabetes without microvascular complications). Dynamic cerebral autoregulation and the steady-state cerebrovascular response to postural change were studied in subjects with DM+ and DM-, in the absence of cardiovascular autonomic neuropathy, and in CTRL (healthy control) subjects. The relationship between spontaneous changes in MCA V(mean) (middle cerebral artery mean blood velocity) and MAP (mean arterial pressure) was evaluated using frequency domain analysis. In the low-frequency region (0.07-0.15 Hz), the phase lead of the MAP-to-MCA V(mean) transfer function was 52+/-10 degrees in CTRL subjects, reduced in subjects with DM- (40+/-6 degrees ; P<0.01 compared with CTRL subjects) and impaired in subjects with DM+ (30+/-5 degrees ; P<0.01 compared with subjects with DM-), indicating less dampening of blood pressure oscillations by affected dynamic cerebral autoregulation. The steady-state response of MCA V(mean) to postural change was comparable for all groups (-12+/-6% in CTRL subjects, -15+/-6% in subjects with DM- and -15+/-7% in subjects with DM+). HbA(1c) (glycated haemoglobin) and the duration of diabetes, but not blood pressure, were determinants of transfer function phase. In conclusion, dysfunction of dynamic cerebral autoregulation in subjects with Type 2 diabetes appears to be an early manifestation of microvascular disease prior to the clinical expression of diabetic nephropathy, retinopathy or cardiovascular autonomic neuropathy.

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO2 responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO2 responsiveness is impaired in SCD and related to hemolytic anemia. Transcranial Doppler-determined mean cerebral blood flow velocity (V(mean)), near-infrared spectroscopy-determined cerebral oxygenation, and end-tidal CO2 tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO2 responsiveness was quantified as Delta% V(mean) and Deltamicromol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO2 tension. Both ways of measurements revealed lower cerebrovascular CO2 responsiveness in SCD patients versus controls (V(mean), 3.7, 3.1-4.7 vs 5.9, 4.6-6.7 Delta% V(mean) per mm Hg, P < .001; oxyhemoglobin, 0.36, 0.14-0.82 vs 0.78, 0.61-1.22 Deltamicromol/L per mm Hg, P = .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 Deltamicromol/L per mm Hg, P = .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 Deltamicromol/L per mm Hg, P = .038). Cerebrovascular CO2 responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO2 responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke.

Intensive Blood Pressure Control Affects Cerebral Blood Flow in Type 2 Diabetes Mellitus Patients

Type 2 diabetes mellitus is associated with microvascular complications, hypertension, and impaired dynamic cerebral autoregulation. Intensive blood pressure (BP) control in hypertensive type 2 diabetic patients reduces their risk of stroke but may affect cerebral perfusion. Systemic hemodynamic variables and transcranial Doppler-determined cerebral blood flow velocity (CBFV), cerebral CO2 responsiveness, and cognitive function were determined after 3 and 6 months of intensive BP control in 17 type 2 diabetic patients with microvascular complications (T2DM+), in 18 diabetic patients without (T2DM−) microvascular complications, and in 16 nondiabetic hypertensive patients. Cerebrovascular reserve capacity was lower in T2DM+ versus T2DM− and nondiabetic hypertensive patients (4.6±1.1 versus 6.0±1.6 [P<0.05] and 6.6±1.7 [P<0.01], &Dgr;%mean CBFV/mm Hg). After 6 months, the attained BP was comparable among the 3 groups. However, in contrast to nondiabetic hypertensive patients, intensive BP control reduced CBFV in T2DM− (58±9 to 54±12 cm · s−1) and T2DM+ (57±13 to 52±11 cm · s−1) at 3 months, but CBFV returned to baseline at 6 months only in T2DM−, whereas the reduction in CBFV progressed in T2DM+ (to 48±8 cm · s−1). Cognitive function did not change during the 6 months. Static cerebrovascular autoregulation appears to be impaired in type 2 diabetes mellitus, with a transient reduction in CBFV in uncomplicated diabetic patients on tight BP control, but with a progressive reduction in CBFV in diabetic patients with microvascular complications, indicating that maintenance of cerebral perfusion during BP treatment depends on the progression of microvascular disease. We suggest that BP treatment should be individualized, aiming at a balance between BP reduction and maintenance of CBFV.

Active standing reduces wave reflection in the presence of increased peripheral resistance in young and old healthy individuals.

Objective Pressure wave reflections are age-dependent and generally assumed to increase with increasing peripheral resistance. We sought to determine the effect of standing on wave reflection in healthy older and younger individuals and the influence of increased peripheral resistance. Methods During supine rest and active standing, continuous finger arterial blood pressure was measured. Data obtained in the supine period and after 1 and 5 min standing were analysed. Aortic pressure and flow, calculated from finger pressure, were used to derive forward and backward pressure waves, reflection magnitude (ratio of backward and forward pressure waves), augmentation index, and peripheral resistance. Results Fifteen healthy older (aged 53 ± 7 years) and 15 healthy younger (aged 29 ± 5 years) individuals were included. In both groups, upon standing, stroke volume, cardiac output and pulse pressure decreased with an increase in heart rate and in diastolic pressure. In the older group peripheral resistance increased from 1.3 ± 0.4 to 1.5 ± 0.4 and 1.5 ± 0.4 for supine, 1 and 5 min standing, whereas reflection magnitude decreased from 0.67 ± 0.1 to 0.61 ± 0.1 and 0.61 ± 0.1, and augmentation index from 33 ± 11 to 23 ± 12 and 25 ± 11. In the younger group peripheral resistance increased from 0.9 ± 0.2 to 1.1 ± 0.2 and 1.1 ± 0.2, whereas reflection magnitude decreased from 0.55 ± 0.05 to 0.48 ± 0.05 and 0.49 ± 0.05 and augmentation index from 18 ± 11 to 1 ± 18 and 4 ± 19. Conclusion With standing, haemodynamic variables change similarly in older and younger individuals. The opposite changes in reflection magnitude and peripheral resistance suggest that reflection and pressure augmentation are not solely dependent on peripheral resistance.

Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease

Background and Purpose— Sickle cell disease (SCD) is associated with cerebral hyperperfusion and an increased risk of stroke. Also, both recurrent microvascular obstruction and chronic hemolysis affect endothelial function, potentially interfering with systemic and cerebral blood flow control. We addressed the question whether cerebrovascular control in patients with SCD is affected and related to hemolysis. Methods— Systemic and cerebrovascular control were studied in 18 patients with SCD and 10 healthy subjects. Dynamic cerebral autoregulation was evaluated by transfer function analysis assessing the relationship between mean cerebral blood flow velocity and mean arterial pressure. Results— Normal baroreflex sensitivity and postural cardiovascular reflex responses indicated integrity of systemic cardiovascular control. In the low- (0.07 to 0.15 Hz) frequency region, mean arterial pressure variability was comparable for both groups, but a larger mean cerebral blood flow velocity variability in SCD (6.1 [4.6 to 7.0] versus 4.2 [2.6 to 5.2] [cm·s−1]2·Hz−1; P<0.05) indicated a reduced capacity to buffer the transfer of blood pressure surges to the cerebral tissue. Impairment of dynamic cerebrovascular control was confirmed by a reduced mean arterial pressure-to-mean cerebral blood flow velocity transfer function phase lead in SCD versus healthy subjects (32±17° versus 50±19°, P<0.05) that was unrelated to the severity of hemolysis. Conclusions— In patients with SCD, dynamic cerebral autoregulation is impaired but appears unrelated to hemolysis.

Cerebral Hemodynamics During Treatment With Sodium Nitroprusside Versus Labetalol in Malignant Hypertension

In patients with malignant hypertension, immediate blood pressure reduction is indicated to prevent further organ damage. Because cerebral autoregulatory capacity is impaired in these patients, a pharmacologically induced decline of blood pressure reduces cerebral blood flow with the danger of cerebral hypoperfusion. We compared the reduction in transcranial Doppler–determined middle cerebral artery blood velocity during blood pressure lowering with sodium nitroprusside with that of labetalol. Therefore, in 15 patients, fulfilling World Health Organization criteria for malignant hypertension, beat-to-beat mean arterial pressure, systemic vascular resistance (Modelflow), mean middle cerebral artery blood velocity, and cerebrovascular resistance index (mean blood pressure:mean middle cerebral artery blood flow velocity ratio), were monitored during treatment with sodium nitroprusside (n=8) or labetalol (n=7). The reduction in mean arterial blood pressure with sodium nitroprusside (−28±3%; mean±SEM) and labetalol (−28±4%) was comparable. With labetalol, both systemic and cerebral vascular resistance decreased proportionally (−13±10% and −17±5%), whereas with sodium nitroprusside, the decline in systemic vascular resistance was larger than that in cerebral vascular resistance (−53±4% and −7±4%). The rate of reduction in middle cerebral artery blood velocity was smaller with labetalol than with sodium nitroprusside (0.45±0.05% versus 0.78±0.04% cm · s−1 · %mm Hg−1; P<0.05). In conclusion, sodium nitroprusside reduced systemic vascular resistance rather than cerebral vascular resistance with a larger rate of reduction in middle cerebral artery blood velocity, suggesting a preferential blood flow to the low resistance systemic vascular bed rather than the cerebral vascular bed.

Effects of aging on the cerebrovascular orthostatic response

When healthy subjects stand up, it is associated with a reduction in cerebral blood velocity and oxygenation although cerebral autoregulation would be considered to prevent a decrease in cerebral perfusion. Aging is associated with a higher incidence of falls, and in the elderly falls may occur particularly during the adaptation to postural change. This study evaluated the cerebrovascular adaptation to postural change in 15 healthy younger (YNG) vs. 15 older (OLD) subjects by recordings of the near-infrared spectroscopy-determined cerebral oxygenation (cO₂Hb) and the transcranial Doppler-determined mean middle cerebral artery blood velocity (MCA V(mean)). In OLD (59 (52-65) years) vs. YNG (29 (27-33) years), the initial postural decline in mean arterial pressure (-52 ± 3% vs. -67 ± 3%), cO₂Hb (-3.4 ± 2.5 μmoll(-1) vs. -5.3 ± 1.7 μmoll(-1)) and MCA V(mean) (-16 ± 4% vs. -29 ± 3%) was smaller. The decline in MCA V(mean) was related to the reduction in MAP. During prolonged orthostatic stress, the decline in MCA V(mean)and cO(2)Hb in OLD remained smaller. We conclude that with healthy aging the postural reduction in cerebral perfusion becomes less prominent.

Orthostatic leg blood volume changes assessed by near‐infrared spectroscopy

Standing up shifts blood to dependent parts of the body, and blood vessels in the leg become filled. The orthostatic blood volume accumulation in the small vessels is relatively unknown, although these may contribute significantly. We hypothesized that in healthy humans exposed to the upright posture, volume accumulation in small blood vessels contributes significantly to the total fluid volume accumulated in the legs. Considering that near‐infrared spectroscopy (NIRS) tracks postural blood volume changes within the small blood vessels of the lower leg, we evaluated the NIRS‐determined changes in oxygenated (Δ[O2Hb]), deoxygenated (Δ[HHb]) and total haemoglobin tissue concentration (Δ[tHb]) and in total leg volume by strain‐gauge plethysmography during 70 deg head‐up tilt (HUT; n= 7). In a second experiment, spatial and temporal reproducibility were evaluated with three NIRS probes applied on two separate days (n= 8). In response to HUT, an initially fast increase in [O2Hb] was followed by a gradual decline, while [HHb] increased continuously. The increase in [tHb] during HUT was closely related to the increase in total leg volume (r2= 0.95 ± 0.03). After tilt back, [O2Hb] declined below and [HHb] remained above baseline, whereas all NIRS signals gradually returned to baseline. Spatial heterogeneity was observed, and for two probes [tHb] was highly correlated between days (r2= 0.92 ± 0.09 and 0.91 ± 0.12), but less for the third probe (r2= 0.44 ± 0.36). The results suggest a non‐linear accumulation of blood volume in the small vessels of the leg, with an initial fast phase followed by a more gradual increase at least partly contributing to the relocation of fluid during orthostatic stress.

Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (P<0.01), whereas hematocrit was unaffected following acute EPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; P<0.05). Also, both EPO regimes widened the arterial‐to‐jugular O2 differences at rest as well as during normoxic and hypoxic exercise (P<0.01), which indicated reduced cerebral blood flow despite preserved dynamic cerebral autoregulation, and an increase in middle cerebral artery mean blood flow velocity (P<0.05), therefore, reflected vasoconstriction. Thus, administration of EPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.—Rasmussen, P., Kim, Y. S., Krogh‐Madsen, R., Lundby, C., Olsen, N. V., Secher, N. H., van Lieshout, J. J. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans. FASEB J. 26, 1343‐1348 (2012). www.fasebj.org