Central Hypovolemia Detection During Environmental Stress-A Role for Artificial Intelligence?

The first step to exercise is preceded by the required assumption of the upright body position, which itself involves physical activity. The gravitational displacement of blood from the chest to the lower parts of the body elicits a fall in central blood volume (CBV), which corresponds to the fraction of thoracic blood volume directly available to the left ventricle. The reduction in CBV and stroke volume (SV) in response to postural stress, post-exercise, or to blood loss results in reduced left ventricular filling, which may manifest as orthostatic intolerance. When termination of exercise removes the leg muscle pump function, CBV is no longer maintained. The resulting imbalance between a reduced cardiac output (CO) and a still enhanced peripheral vascular conductance may provoke post-exercise hypotension (PEH). Instruments that quantify CBV are not readily available and to express which magnitude of the CBV in a healthy subject should remains difficult. In the physiological laboratory, the CBV can be modified by making use of postural stressors, such as lower body "negative" or sub-atmospheric pressure (LBNP) or passive head-up tilt (HUT), while quantifying relevant biomedical parameters of blood flow and oxygenation. Several approaches, such as wearable sensors and advanced machine-learning techniques, have been followed in an attempt to improve methodologies for better prediction of outcomes and to guide treatment in civil patients and on the battlefield. In the recent decade, efforts have been made to develop algorithms and apply artificial intelligence (AI) in the field of hemodynamic monitoring. Advances in quantifying and monitoring CBV during environmental stress from exercise to hemorrhage and understanding the analogy between postural stress and central hypovolemia during anesthesia offer great relevance for healthy subjects and clinical populations.

Cerebral vs. Cardiovascular Responses to Exercise in Type 2 Diabetic Patients.

The human brain is constantly active and even small limitations to cerebral blood flow (CBF) may be critical for preserving oxygen and substrate supply, e.g., during exercise and hypoxia. Exhaustive exercise evokes a competition for the supply of oxygenated blood between the brain and the working muscles, and inability to increase cardiac output sufficiently during exercise may jeopardize cerebral perfusion of relevance for diabetic patients. The challenge in diabetes care is to optimize metabolic control to slow progression of vascular disease, but likely because of a limited ability to increase cardiac output, these patients perceive aerobic exercise to be more strenuous than healthy subjects and that limits the possibility to apply physical activity as a preventive lifestyle intervention. In this review, we consider the effects of functional activation by exercise on the brain and how it contributes to understanding the control of CBF with the limited exercise tolerance experienced by type 2 diabetic patients. Whether a decline in cerebral oxygenation and thereby reduced neural drive to working muscles plays a role for "central" fatigue during exhaustive exercise is addressed in relation to brain's attenuated vascular response to exercise in type 2 diabetic subjects.

Impaired nocturnal blood pressure dipping in patients with type 2 diabetes mellitus.

Hypertension is a common comorbidity of type 2 diabetes mellitus (T2DM). Both conditions are associated with an increased cardiovascular risk, which is reduced by tight blood pressure (BP) and glycemic control. However, nondipping BP status continues to be an enduring cardiovascular risk factor in T2DM. Cardiovascular autonomic neuropathy and endothelial dysfunction have been proposed as potential mechanisms. This study tested the hypothesis that microvascular disease rather than cardiovascular autonomic neuropathy interferes with the physiological nocturnal BP reduction. Cardiovascular autonomic function and baroreflex sensitivity were determined in 22 type 2 diabetic patients with (DM+) and 23 diabetic patients without (DM-) manifest microvascular disease. BP dipping status was assessed from 24-hour ambulatory BP measurements. Sixteen nondiabetic subjects served as controls (CTRL). Cardiovascular autonomic function was normal in all subjects. Baroreflex sensitivity was lower in DM- compared with CTRL (7.7 ± 3.3 vs. 12.3 ± 8.3 ms·mm Hg-1; P < 0.05) and was further reduced in DM + (4.6 ± 2.0 ms·mm Hg-1; P < 0.01 vs. DM- and CTRL). The nocturnal decline in systolic and diastolic BP was blunted in DM- (12% and 14% vs. 17% and 19% in CTRL; P < 0.05) and even more so in DM+ (8% and 11%; P < 0.05 vs. DM- and P < 0.001 vs. CTRL). A nocturnal reduction in pulse pressure was observed in CTRL and DM- but not in DM+ (P < 0.05 vs. DM- and P < 0.01 vs. CTRL). In T2DM, progression of microvascular disease interferes with the normal nocturnal BP decline and coincides with a persistently increased pulse pressure and reduced baroreflex sensitivity, contributing to their increased cardiovascular risk.

Impaired cerebral blood flow and oxygenation during exercise in type 2 diabetic patients.

Endothelial vascular function and capacity to increase cardiac output during exercise are impaired in patients with type 2 diabetes (T2DM). We tested the hypothesis that the increase in cerebral blood flow (CBF) during exercise is also blunted and, therefore, that cerebral oxygenation becomes affected and perceived exertion increased in T2DM patients. We quantified cerebrovascular besides systemic hemodynamic responses to incremental ergometer cycling exercise in eight male T2DM and seven control subjects. CBF was assessed from the Fick equation and by transcranial Doppler-determined middle cerebral artery blood flow velocity. Cerebral oxygenation and metabolism were evaluated from the arterial-to-venous differences for oxygen, glucose, and lactate. Blood pressure was comparable during exercise between the two groups. However, the partial pressure of arterial carbon dioxide was lower at higher workloads in T2DM patients and their work capacity and increase in cardiac output were only ~80% of that established in the control subjects. CBF and cerebral oxygenation were reduced during exercise in T2DM patients (P < 0.05), and they expressed a higher rating of perceived exertion (P < 0.05). In contrast, CBF increased ~20% during exercise in the control group while the brain uptake of lactate and glucose was similar in the two groups. In conclusion, these results suggest that impaired CBF and oxygenation responses to exercise in T2DM patients may relate to limited ability to increase cardiac output and to reduced vasodilatory capacity and could contribute to their high perceived exertion.

Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular autoregulation at reduced arterial carbon dioxide tension.

OBJECTIVE: The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoregulation in healthy subjects exposed to endotoxemia. DESIGN: Prospective descriptive study. SETTING: Hospital research laboratory. SUBJECTS: Ten healthy young subjects (age: 32 ± 8 yrs [mean ± SD]; weight: 84 ± 10 kg; weight: 184 ± 5 cm; body mass index: 25 ± 2 kg/m2) participated in the study. INTERVENTIONS: Systemic hemodynamics, middle cerebral artery mean flow velocity, and dynamic cerebral autoregulation evaluated by transfer function analysis in the very low (<0.07 Hz), low (0.07-0.15 Hz), and high (>0.15 Hz) frequency ranges were monitored in these volunteers before and after an endotoxin bolus (2 ng/kg; Escherichia coli). MEASUREMENTS AND MAIN RESULTS: Endotoxin increased body temperature of the subjects from 36.8 ± 0.4°C to 38.6 ± 0.5°C (p < .001) and plasma tumor necrosis factor-α from 5.6 (2.8-6.7) pg/mL to 392 (128-2258) pg/mL (p < .02). Endotoxemia had no influence on mean arterial pressure (95 [74-103] mm Hg vs. 92 [78-104] mm Hg; p = .75), but increased cardiac output (8.3 [6.1-9.5] L·min(-1) vs. 6.0 [4.5-8.2] L·min(-1); p = .02) through an elevation in heart rate (82 ± 9 beats·min(-1) vs. 63 ± 10 beats·min(-1); p < .001), whereas arterial carbon dioxide tension (37 ± 5 mm Hg vs. 41 ± 2 mm Hg; p < .05) and middle cerebral artery mean flow velocity (37 ± 9 cm·sec(-1) vs. 47 ± 10 cm·sec(-1); p < .01) were reduced. In regard to dynamic cerebral autoregulation, endotoxemia was associated with lower middle cerebral artery mean flow velocity variability (1.0 ± 1.0 [cm·sec(-1)] Hz vs. 2.8 ± 1.5 [cm·sec(-1)] Hz; p < .001), reduced gain (0.52 ± 0.11 cm·sec(-1) x mm Hg(-1) vs. 0.74 ± 0.17 cm·sec(-1) x mm Hg(-1); p < .05), normalized gain (0.22 ± 0.05 vs. 0.40 ± 0.17%·%; p < .05), and higher mean arterial pressure-to-middle cerebral artery mean flow velocity phase difference (p < .05) in the low frequency range (0.07-0.15 Hz). CONCLUSIONS: These data support that the reduction in arterial carbon dioxide tension explains the improved dynamic cerebral autoregulation and the reduced cerebral perfusion encountered in healthy subjects during endotoxemia.

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.

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 O(2) 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.

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], Δ%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.

Baroreflex sensitivity is higher during acute psychological stress in healthy subjects under ß-adrenergic blockade.

Acute psychological stress challenges the cardiovascular system with an increase in BP (blood pressure), HR (heart rate) and reduced BRS (baroreflex sensitivity). ß-adrenergic blockade enhances BRS during rest, but its effect on BRS during acute psychological stress is unknown. This study tested the hypothesis that BRS is higher during acute psychological stress in healthy subjects under ß-adrenergic blockade. Twenty healthy novice male bungee jumpers were randomized and studied with (PROP, n=10) or without (CTRL, n=10) propranolol. BP and HR responses and BRS [cross-correlation time-domain (BRSTD) and cross-spectral frequency-domain (BRSFD) analysis] were evaluated from 30 min prior up to 2 h after the jump. HR, cardiac output and pulse pressure were lower in the PROP group throughout the study. Prior to the bungee jump, BRS was higher in the PROP group compared with the CTRL group [BRSTD: 28 (24-42) compared with 17 (16-28) ms·mmHg-1, P<0.05; BRSFD: 27 (20-34) compared with 14 (9-19) ms·mmHg-1, P<0.05; values are medians (interquartile range)]. BP declined after the jump in both groups, and post-jump BRS did not differ between the groups. In conclusion, during acute psychological stress, BRS is higher in healthy subjects treated with non-selective ß-adrenergic blockade with significantly lower HR but comparable BP.

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.

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.

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 x s(-1)](2) x 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 degrees versus 50+/-19 degrees , 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.

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.

Management of initial orthostatic hypotension: lower body muscle tensing attenuates the transient arterial blood pressure decrease upon standing from squatting.

IOH (initial orthostatic hypotension) comprises symptoms of cerebral hypoperfusion caused by an abnormally large transient MAP (mean arterial pressure) decrease 5-15 s after arising from a supine, sitting or squatting position. Few treatment options are available. In the present study, we set out to test the hypothesis that LBMT (lower body muscle tensing) attenuates IOH after rising from squatting and its symptoms in daily life. A total of 13 IOH patients (nine men; median age, 27 years) rose from squatting twice, once with LBMT and once without. In addition, seven healthy volunteers (five men; median age, 27 years) were studied in a cross-over study design. They stood up from the squatting position three times, once combined with LBMT. Blood pressure (Finometer) was measured continuously, and CO (cardiac output) by Modelflow and TPR (total peripheral resistance) were computed. MAP, CO and TPR were compared without and with LBMT. Using a questionnaire, the perceived effectiveness of LBMT in the patients' daily lives was evaluated. With LBMT, the minimal MAP after standing up was higher in both groups (19 mmHg in patients and 13 mmHg in healthy subjects). In healthy subjects, the underlying mechanism was a blunted TPR decrease (to 47% compared with 60%; P<0.05), whereas in the patients no clear CO or TPR pattern was discernible. During follow-up, eight out of ten patients using LBMT reported fewer IOH symptoms. In conclusion, LBMT is a new intervention to attenuate the transient blood pressure decrease after standing up from squatting, and IOH patients should be advised about the use of this manoeuvre.

Effects of hyperglycemia on the cerebrovascular response to rhythmic handgrip exercise.

Dynamic cerebral autoregulation (CA) is challenged by exercise and may become less effective when exercise is exhaustive. Exercise may increase arterial glucose concentration, and we evaluated whether the cerebrovascular response to exercise is affected by hyperglycemia. The effects of a hyperinsulinemic euglycemic clamp (EU) and hyperglycemic clamp (HY) on the cerebrovascular (CVRI) and systemic vascular resistance index (SVRI) responses were evaluated in seven healthy subjects at rest and during rhythmic handgrip exercise. Transfer function analysis of the dynamic relationship between beat-to-beat changes in mean arterial pressure and middle cerebral artery (MCA) mean blood flow velocity (V(mean)) was used to assess dynamic CA. At rest, SVRI decreased with HY and EU (P < 0.01). CVRI was maintained with EU but became reduced with HY [11% (SD 3); P < 0.01], and MCA V(mean) increased (P < 0.05), whereas brain catecholamine uptake and arterial Pco(2) did not change significantly. HY did not affect the normalized low-frequency gain between mean arterial pressure and MCA V(mean) or the phase shift, indicating maintained dynamic CA. With HY, the increase in CVRI associated with exercise was enhanced (19 +/- 7% vs. 9 +/- 7%; P < 0.05), concomitant with a larger increase in heart rate and cardiac output and a larger reduction in SVRI (22 +/- 4% vs. 14 +/- 2%; P < 0.05). Thus hyperglycemia lowered cerebral vascular tone independently of CA capacity at rest, whereas dynamic CA remained able to modulate cerebral blood flow around the exercise-induced increase in MCA V(mean). These findings suggest that elevated blood glucose does not explain that dynamic CA is affected during intense exercise.