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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.

Purpose: During cycling, the variation in cardiac stroke volume (SVV) is similar to that at rest. However, SVV may be influenced by ventilation at the start of cycling, e.g., by a Valsalva-like maneuver used to stabilize the body. This study evaluated the influence of ventilation on SV during initiation of cycling. Methods: Ten healthy recreationally physical active males (mean ± SD: age 26 ± 3 years, height 184 ± 9 cm, weight 85 ± 9 kg) cycled on an ergometer for four 30 s intervals at submaximal workloads while synchronizing ventilatory and cardiovascular variables derived from gas exchange and arterial pulse contour analysis, respectively. Results: At exercise onset, cardiac output increased by an instantaneous rise in heart rate and SV (P < 0.05). In contrast, blood pressure increased only after 15 s (P < 0.05), reflected in a decline in total peripheral resistance from exercise onset (P < 0.05). SVV was similar at rest (20 ± 6%) and during exercise (21 ± 5%) except for the first 5 s of exercise when a ~ 2.5-fold elevation (47 ± 6%; P < 0.05) was correlated to variation in respiratory frequency (= 0.71, P = 0.02) and tidal volume (R = 0.66, P = 0.04) but not to variation in heart rate or blood pressure. Stepwise multiple regression analysis indicated a respiratory frequency influence on SVV at the onset of ergometer cycling. Conclusion: The data provide evidence for a ventilatory influence on SVV at the onset of cycling exercise.

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.

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status., ImPhys/Quantitative Imaging

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status., ImPhys/Quantitative Imaging

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.

A siphon is suggested to support cerebral blood flow but appears not to be established because internal jugular venous (IJV) pressure is close to zero in upright humans. Thus, in eleven young healthy males, IJV pressure was 9 ± 1 mmHg (mean ± SE) when supine and fell to 3 ± 1 mmHg when seated, and middle cerebral artery mean blood velocity (MCA Vmean; P < 0.007) and the near-infrared spectroscopy-determined frontal lobe oxygenation (ScO2; P = 0.028) also decreased. Another subject, however, developed (pre)syncopal symptoms while seated and his IJV pressure decreased to -17 mmHg. Furthermore, his MCA Vmean decreased and yet within the time of observation ScO2 was not necessarily affected. These findings support the hypothesis that a negative IJV pressure that is a prerequisite for creation of a siphon provokes venous collapse inside the dura, and thereby limits rather than supports CBF.

A siphon is suggested to support cerebral blood flow but appears not to be established because internal jugular venous (IJV) pressure is close to zero in upright humans. Thus, in eleven young healthy males, IJV pressure was 9 ± 1 mmHg (mean ± SE) when supine and fell to 3 ± 1 mmHg when seated, and middle cerebral artery mean blood velocity (MCA Vmean; P < 0.007) and the near-infrared spectroscopy-determined frontal lobe oxygenation (ScO2; P = 0.028) also decreased. Another subject, however, developed (pre)syncopal symptoms while seated and his IJV pressure decreased to -17 mmHg. Furthermore, his MCA Vmean decreased and yet within the time of observation ScO2 was not necessarily affected. These findings support the hypothesis that a negative IJV pressure that is a prerequisite for creation of a siphon provokes venous collapse inside the dura, and thereby limits rather than supports CBF.

We evaluated cerebral perfusion, oxygenation, and metabolism in eleven young (age 22 ± 1 years) and nine older (age 66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% W(max)), high (75% W(ma)) and exhaustive (100% W(max)) workloads. Mean middle cerebral artery blood velocity (MCA V(mean)), mean arterial pressure (MAP), cardiac output (CO) and the partial pressure of arterial carbon dioxide (PaCO(2)) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O(2)), glucose and lactate across the brain. The molar ratio between the cerebral uptake of O(2) versus carbohydrate (O(2)-carbohydrate index; O(2) / [glucose + 0.5 lactate]; OCI), the cerebral metabolic rate of O(2) (CMRO(2)) and changes in mitochondrial O(2) tension (P(mito)O(2)) were calculated. W(max) was ~33% lower in the older group. Exercise increased MAP and CO in both groups (P

We evaluated cerebral perfusion, oxygenation, and metabolism in eleven young (age 22 ± 1 years) and nine older (age 66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% W(max)), high (75% W(ma)) and exhaustive (100% W(max)) workloads. Mean middle cerebral artery blood velocity (MCA V(mean)), mean arterial pressure (MAP), cardiac output (CO) and the partial pressure of arterial carbon dioxide (PaCO(2)) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O(2)), glucose and lactate across the brain. The molar ratio between the cerebral uptake of O(2) versus carbohydrate (O(2)-carbohydrate index; O(2) / [glucose + 0.5 lactate]; OCI), the cerebral metabolic rate of O(2) (CMRO(2)) and changes in mitochondrial O(2) tension (P(mito)O(2)) were calculated. W(max) was ~33% lower in the older group. Exercise increased MAP and CO in both groups (P

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10 cmH(2)O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P <0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2 mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8 mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA V(mean) was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2 mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.

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

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10 cmH(2)O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P <0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2 mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8 mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA V(mean) was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2 mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.

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

BACKGROUND. An increase in total peripheral resistance (TPR) usually increases arterial wave reflection. During passive head-up tilt (HUT), however, arterial wave reflection decreases with increasing TPR. This study addressed whether arterial wave reflection gradually decreases during HUT. METHODS. In 10 healthy volunteers (22-39 years, nine males), we recorded finger arterial pressures in supine position (0°), and 30°and 70°degrees HUT and active standing (90°). Aortic pressure was constructed from the finger pressure signal and hemodynamics were calculated. Arterial wave reflection was quantified as the augmentation index (AIx) and the reflection magnitude (RM). RESULTS. During HUT, heart rate increased (p <0.001), stroke volume and cardiac output decreased (p <0.001 and p <0.01), diastolic blood pressure increased (p <0.001), whereas systolic blood pressure did not change. TPR increased from 0.9 dyn s/cm(5) at 0? to 1.2, 1.4 and 1.4 dyn s/cm(5) at 30°, 70° and 90° (p <0.001). AIx fell gradually from 25% at 0°to 16%, -1% and -10% at 30°, 70° and 90° (p <0.001). The RM decreased from 0.572 at 0°to 0.456 at 90° (p <0.001). CONCLUSION. From supine to upright, arterial wave reflection represented as AIx and RM gradually decreases in the presence of increasing TPR.

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], ¿%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.

Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (Vmean) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O2 uptake: 69 ± 7 vs. 42 ± 5 ml O2·min-1·kg-1; n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA Vmean (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P < 0.01) and MCA Vmean (15 ± 1 vs. 11 ± 1 s, P < 0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA Vmean/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA Vmean phase in both groups but ~40% higher normalized MAP to MCA Vmean low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA Vmean and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines., Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (V(mean)) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O(2) uptake: 69 ± 7 vs. 42 ± 5 ml O(2)·min(-1)·kg(-1); n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA V(mean) (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P <0.01) and MCA V(mean) (15 ± 1 vs. 11 ± 1 s, P <0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA V(mean)/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA V(mean) phase in both groups but ~40% higher normalized MAP to MCA V(mean) low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA V(mean) and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines.

BACKGROUND. An increase in total peripheral resistance (TPR) usually increases arterial wave reflection. During passive head-up tilt (HUT), however, arterial wave reflection decreases with increasing TPR. This study addressed whether arterial wave reflection gradually decreases during HUT. METHODS. In 10 healthy volunteers (22-39 years, nine males), we recorded finger arterial pressures in supine position (0°), and 30°and 70°degrees HUT and active standing (90°). Aortic pressure was constructed from the finger pressure signal and hemodynamics were calculated. Arterial wave reflection was quantified as the augmentation index (AIx) and the reflection magnitude (RM). RESULTS. During HUT, heart rate increased (p <0.001), stroke volume and cardiac output decreased (p <0.001 and p <0.01), diastolic blood pressure increased (p <0.001), whereas systolic blood pressure did not change. TPR increased from 0.9 dyn s/cm(5) at 0? to 1.2, 1.4 and 1.4 dyn s/cm(5) at 30°, 70° and 90° (p <0.001). AIx fell gradually from 25% at 0°to 16%, -1% and -10% at 30°, 70° and 90° (p <0.001). The RM decreased from 0.572 at 0°to 0.456 at 90° (p <0.001). CONCLUSION. From supine to upright, arterial wave reflection represented as AIx and RM gradually decreases in the presence of increasing TPR.

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], ¿%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.

Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (Vmean) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O2 uptake: 69 ± 7 vs. 42 ± 5 ml O2·min-1·kg-1; n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA Vmean (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P < 0.01) and MCA Vmean (15 ± 1 vs. 11 ± 1 s, P < 0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA Vmean/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA Vmean phase in both groups but ~40% higher normalized MAP to MCA Vmean low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA Vmean and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines., Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (V(mean)) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O(2) uptake: 69 ± 7 vs. 42 ± 5 ml O(2)·min(-1)·kg(-1); n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA V(mean) (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P <0.01) and MCA V(mean) (15 ± 1 vs. 11 ± 1 s, P <0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA V(mean)/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA V(mean) phase in both groups but ~40% higher normalized MAP to MCA V(mean) low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA V(mean) and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines.

BACKGROUND. An increase in total peripheral resistance (TPR) usually increases arterial wave reflection. During passive head-up tilt (HUT), however, arterial wave reflection decreases with increasing TPR. This study addressed whether arterial wave reflection gradually decreases during HUT. METHODS. In 10 healthy volunteers (22-39 years, nine males), we recorded finger arterial pressures in supine position (0°), and 30°and 70°degrees HUT and active standing (90°). Aortic pressure was constructed from the finger pressure signal and hemodynamics were calculated. Arterial wave reflection was quantified as the augmentation index (AIx) and the reflection magnitude (RM). RESULTS. During HUT, heart rate increased (p <0.001), stroke volume and cardiac output decreased (p <0.001 and p <0.01), diastolic blood pressure increased (p <0.001), whereas systolic blood pressure did not change. TPR increased from 0.9 dyn s/cm(5) at 0? to 1.2, 1.4 and 1.4 dyn s/cm(5) at 30°, 70° and 90° (p <0.001). AIx fell gradually from 25% at 0°to 16%, -1% and -10% at 30°, 70° and 90° (p <0.001). The RM decreased from 0.572 at 0°to 0.456 at 90° (p <0.001). CONCLUSION. From supine to upright, arterial wave reflection represented as AIx and RM gradually decreases in the presence of increasing TPR.

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], ¿%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.

Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (Vmean) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O2 uptake: 69 ± 7 vs. 42 ± 5 ml O2·min-1·kg-1; n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA Vmean (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P < 0.01) and MCA Vmean (15 ± 1 vs. 11 ± 1 s, P < 0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA Vmean/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA Vmean phase in both groups but ~40% higher normalized MAP to MCA Vmean low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA Vmean and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines., Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (V(mean)) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O(2) uptake: 69 ± 7 vs. 42 ± 5 ml O(2)·min(-1)·kg(-1); n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA V(mean) (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P <0.01) and MCA V(mean) (15 ± 1 vs. 11 ± 1 s, P <0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA V(mean)/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA V(mean) phase in both groups but ~40% higher normalized MAP to MCA V(mean) low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA V(mean) and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines.

The Frank-Starling mechanism describes the relationship between stroke volume and preload to the heart, or the volume of blood that is available to the heart--the central blood volume. Understanding the role of the central blood volume for cardiovascular control has been complicated by the fact that a given central blood volume may be associated with markedly different central vascular pressures. The central blood volume varies with posture and, consequently, stroke volume and cardiac output (Q) are affected, but with the increased central blood volume during head-down tilt, stroke volume and Q do not increase further indicating that in the supine resting position the heart operates on the plateau of the Frank-Starling curve which, therefore, may be taken as a functional definition of normovolaemia. Since the capacity of the vascular system surpasses the blood volume, orthostatic and environmental stress including bed rest/microgravity, exercise and training, thermal loading, illness, and trauma/haemorrhage is likely to restrict venous return and Q. Consequently the cardiovascular responses are determined primarily by their effect on the central blood volume. Thus during environmental stress, flow redistribution becomes dependent on sympathetic activation affecting not only skin and splanchnic blood flow, but also flow to skeletal muscles and the brain. This review addresses the hypothesis that deviations from normovolaemia significantly influence these cardiovascular responses.

The Frank-Starling mechanism describes the relationship between stroke volume and preload to the heart, or the volume of blood that is available to the heart--the central blood volume. Understanding the role of the central blood volume for cardiovascular control has been complicated by the fact that a given central blood volume may be associated with markedly different central vascular pressures. The central blood volume varies with posture and, consequently, stroke volume and cardiac output (Q) are affected, but with the increased central blood volume during head-down tilt, stroke volume and Q do not increase further indicating that in the supine resting position the heart operates on the plateau of the Frank-Starling curve which, therefore, may be taken as a functional definition of normovolaemia. Since the capacity of the vascular system surpasses the blood volume, orthostatic and environmental stress including bed rest/microgravity, exercise and training, thermal loading, illness, and trauma/haemorrhage is likely to restrict venous return and Q. Consequently the cardiovascular responses are determined primarily by their effect on the central blood volume. Thus during environmental stress, flow redistribution becomes dependent on sympathetic activation affecting not only skin and splanchnic blood flow, but also flow to skeletal muscles and the brain. This review addresses the hypothesis that deviations from normovolaemia significantly influence these cardiovascular responses.

Udgivelsesdato: 2010-Jan

Udgivelsesdato: 2010, Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure. This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between MCA Vmean (middle cerebral artery blood velocity; using transcranial Doppler ultrasound), frontal lobe oxygenation [O2Hb (oxyhaemoglobin)] and MAP (mean arterial pressure), CO (cardiac output) and TPR (total peripheral resistance) in six patients (aged 37-67 years; three women) and age- and gender-matched controls during leg crossing. In the patients, leg crossing increased MAP from 58 (42-79) to 72 (52-89) compared with 84 (70-95) to 90 (74-94) mmHg in the controls. MCA Vmean increased from 55 (38-77) to 63 (45-80) and from 56 (46-77) to 64 (46-80) cm/s respectively (P<0.05), with a larger rise in O2Hb [1.12 (0.52-3.27)] in the patients compared with the controls [0.83 (-0.11 to 2.04) micromol/l]. In the control subjects, CO increased 11% (P<0.05) with no change in TPR. By contrast, in the patients, CO increased 9% (P<0.05), but also TPR increased by 13% (P<0.05). In conclusion, leg crossing improves cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects, cerebral perfusion and oxygenation were improved by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure, cerebral perfusion and oxygenation were improved through a rise in MAP due to increments in both CO and TPR.

Udgivelsesdato: 2010-Aug

Udgivelsesdato: 2010-Jan

Udgivelsesdato: 2010, Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure. This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between MCA Vmean (middle cerebral artery blood velocity; using transcranial Doppler ultrasound), frontal lobe oxygenation [O2Hb (oxyhaemoglobin)] and MAP (mean arterial pressure), CO (cardiac output) and TPR (total peripheral resistance) in six patients (aged 37-67 years; three women) and age- and gender-matched controls during leg crossing. In the patients, leg crossing increased MAP from 58 (42-79) to 72 (52-89) compared with 84 (70-95) to 90 (74-94) mmHg in the controls. MCA Vmean increased from 55 (38-77) to 63 (45-80) and from 56 (46-77) to 64 (46-80) cm/s respectively (P<0.05), with a larger rise in O2Hb [1.12 (0.52-3.27)] in the patients compared with the controls [0.83 (-0.11 to 2.04) micromol/l]. In the control subjects, CO increased 11% (P<0.05) with no change in TPR. By contrast, in the patients, CO increased 9% (P<0.05), but also TPR increased by 13% (P<0.05). In conclusion, leg crossing improves cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects, cerebral perfusion and oxygenation were improved by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure, cerebral perfusion and oxygenation were improved through a rise in MAP due to increments in both CO and TPR.

Udgivelsesdato: 2010-Aug

Udgivelsesdato: 2009-Jun

Udgivelsesdato: 2009-Jun

Udgivelsesdato: 2008-Oct, 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 O(2) uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O(2)/(glucose+(1/2) 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 beta(1)- and beta(2)-adrenergic receptor blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-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.

Udgivelsesdato: 2008-Oct, 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 O(2) uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O(2)/(glucose+(1/2) 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 beta(1)- and beta(2)-adrenergic receptor blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-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.

Udgivelsesdato: 2006-Nov, Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/- 4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01). Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and 115 +/- 4 micromol/l, respectively, but it did not significantly influence the L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not correlate significantly, neither to the arterial lactate nor to the pyruvate concentrations. These results support that the arterial plasma L/P ratio modulates cerebral blood flow during cerebral activation independently from the plasma glucose concentration.

Udgivelsesdato: 2006-Nov, Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/- 4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01). Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and 115 +/- 4 micromol/l, respectively, but it did not significantly influence the L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not correlate significantly, neither to the arterial lactate nor to the pyruvate concentrations. These results support that the arterial plasma L/P ratio modulates cerebral blood flow during cerebral activation independently from the plasma glucose concentration.

Udgivelsesdato: 2006-Nov, Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/- 4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01). Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and 115 +/- 4 micromol/l, respectively, but it did not significantly influence the L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not correlate significantly, neither to the arterial lactate nor to the pyruvate concentrations. These results support that the arterial plasma L/P ratio modulates cerebral blood flow during cerebral activation independently from the plasma glucose concentration.

In patients with recurrent syncope, monitoring of intra-arterial pressure during orthostatic stress testing is recommended because of the potentially sudden and rapid development of hypotension. Replacing brachial arterial pressure (BAP) by the non-invasively obtained finger arterial pressure (FinAP) has advantages because catheterization in itself may provoke a syncope.

In patients with recurrent syncope, monitoring of intra-arterial pressure during orthostatic stress testing is recommended because of the potentially sudden and rapid development of hypotension. Replacing brachial arterial pressure (BAP) by the non-invasively obtained finger arterial pressure (FinAP) has advantages because catheterization in itself may provoke a syncope.