Niels D. Olesen

Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals

•  The influence of normative ageing on cerebral perfusion, oxygenation and metabolism during exercise is not well known. •  This study assessed cerebral perfusion and concentration differences for oxygen, glucose and lactate across the brain, in young and elderly individuals at rest and during incremental exercise to exhaustion. •  We observed that during submaximal exercise (at matched relative intensities) and during maximal exercise, cerebral perfusion was reduced in older individuals compared with young individuals, while the cerebral metabolic rate for oxygen and uptake of glucose and lactate were similar. •  The results indicate that the age‐related reduction in cerebral perfusion during exercise does not affect brain uptake of lactate and glucose.

External carotid artery flow maintains near infrared spectroscopy-determined frontal lobe oxygenation during ephedrine administration

BACKGROUND Phenylephrine and ephedrine affect frontal lobe oxygenation ([Formula: see text]) differently when assessed by spatially resolved near infrared spectroscopy. We evaluated the effect of phenylephrine and ephedrine on extra- vs intra-cerebral blood flow and on [Formula: see text]. METHODS In 10 healthy males (age 20-54 yr), phenylephrine or ephedrine was infused for an ∼20 mm Hg increase in mean arterial pressure. Cerebral oxygenation (SavO₂) was calculated from the arterial and jugular bulb oxygen saturations. Blood flow in the internal carotid artery (ICAf) and blood flow in the external carotid artery (ECAf) were assessed by duplex ultrasonography. Invos-5100c (SinvosO₂) and Foresight (SforeO₂) determined [Formula: see text] while forehead skin oxygenation (SskinO₂) was assessed. RESULTS Phenylephrine reduced SforeO₂ by 6.9% (95% confidence interval: 4.8-9.0%; P<0.0001), SinvosO₂ by 10.5 (8.2-12.9%; P<0.0001), and ECAf (6-28%; P=0.0001), but increased ICAf (5-21%; P=0.003) albeit with no consequence for SskinO₂ or SavO₂. In contrast, SforeO₂ was maintained with administration of ephedrine while SinvosO₂ and SavO₂ decreased [by 3.1 (0.7-4.5%; P=0.017) and 2.1 (0.5-3.3%; P=0.012)] as arterial carbon dioxide pressure decreased (P=0.003). ICAf was stable and ECAf increased by 11 (4-18%; P=0.005) with administration of ephedrine while SskinO₂ did not change. CONCLUSIONS The effect of phenylephrine on ScO₂ is governed by a decrease in external carotid blood flow since it increases cerebral blood flow as determined by flow in the internal carotid artery. In contrast, ScO₂ is largely maintained with administration of ephedrine because blood flow to extracerebral tissue increases.

Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men

High‐intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after reρeated HIIE, perhaρs because of lower lactate availability for the brain. This investigation examined whether imρroved EF after exercise relates to brain lactate uρtake. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine arterial‐venous differences across the brain for lactate (a‐v difflactate), glucose (a‐v diffglucose), oxygen (a‐v diffoxygen), and brain‐derived neurotrophic factor (BDNF; a‐v diffBDNF). EF was evaluated by the color‐word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a‐v diffglucose was unchanged, whereas the a‐v diffBDNF increased similarly after both HIIEs, and the a‐v difflactate increased, but the increase was attenuated after the second HIIE, compared with the first HIIE (P <0.05). The EF after HIIE correlated with the a‐v difflactate(r2 = 0.62; P < 0.01). We propose that attenuated improvement in EF after repeated HIIE relates to reduced cerebral lactate metabolism and is, thereby, linked to systemic metabolism as an example of the lactate shuttle mechanism.— Hashimoto, T., Tsukamoto, H., Takenaka, S., Olesen, N. D., Petersen, L. G., Sørensen, H., Nielsen, H. B., Secher, N. H., Ogoh, S. Maintained exercise‐enhanced brain executive function related to cerebral lactate metabolism in men. FASEB J. 32, 1417‐1427 (2018). www.fasebj.org

Glycopyrrolate does not influence the visual or motor-induced increase in regional cerebral perfusion.

Acetylcholine may contribute to the increase in regional cerebral blood flow (rCBF) during cerebral activation since glycopyrrolate, a potent inhibitor of acetylcholine, abolishes the exercise-induced increase in middle cerebral artery mean flow velocity. We tested the hypothesis that cholinergic vasodilatation is important for the increase in rCBF during cerebral activation. The subjects were 11 young healthy males at an age of 24 ± 3 years (mean ± SD). We used arterial spin labeling and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to evaluate rCBF with and without intravenous glycopyrrolate during a handgrip motor task and visual stimulation. Glycopyrrolate increased heart rate from 56 ± 9 to 114 ± 14 beats/min (mean ± SD; p < 0.001), mean arterial pressure from 86 ± 8 to 92 ± 12 mmHg, and cardiac output from 5.6 ± 1.4 to 8.0 ± 1.7 l/min. Glycopyrrolate had, however, no effect on the arterial spin labeling or BOLD responses to the handgrip motor task or to visual stimulation. This study indicates that during a handgrip motor task and visual stimulation, the increase in rCBF is unaffected by blockade of acetylcholine receptors by glycopyrrolate. Further studies on the effect of glycopyrrolate on middle cerebral artery diameter are needed to evaluate the influence of glycopyrrolate on mean flow velocity during intense exercise.

Case report: (Pre)syncopal symptoms associated with a negative internal jugular venous pressure

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.

Impaired Cerebral Autoregulation during Head Up Tilt in Patients with Severe Brain Injury

Early mobilization is of importance for improving long-term outcome for patients after severe acquired brain injury. A limiting factor for early mobilization by head-up tilt is orthostatic intolerance. The purpose of the present study was to examine cerebral autoregulation in patients with severe acquired brain injury and a low level of consciousness. Fourteen patients with severe acquired brain injury and orthostatic intolerance and fifteen healthy volunteers were enrolled. Blood pressure was evaluated by pulse contour analysis, heart rate and RR-intervals were determined by electrocardiography, middle cerebral artery velocity was evaluated by transcranial Doppler, and near-infrared spectroscopy determined frontal lobe oxygenation in the supine position and during head-up tilt. Cerebral autoregulation was evaluated as the mean flow index calculated as the ratio between middle cerebral artery mean velocity and estimated cerebral perfusion pressure. Patients with acquired brain injury presented an increase in mean flow index during head-up tilt indicating impaired autoregulation (P < 0.001). Spectral analysis of heart rate variability in the frequency domain revealed lower magnitudes of ~0.1 Hz spectral power in patients compared to healthy controls suggesting baroreflex dysfunction. In conclusion, patients with severe acquired brain injury and orthostatic intolerance during head-up tilt have impaired cerebral autoregulation more than one month after brain injury.

Carotid baroreflex function at the onset of cycling in men

Arterial baroreflex function is important for blood pressure control during exercise, but its contribution to cardiovascular adjustments at the onset of cycling exercise remains unclear. Fifteen healthy male subjects (24 ± 1 yr) performed 45-s trials of low- and moderate-intensity cycling, with carotid baroreceptor stimulation by neck suction at -60 Torr applied 0-5, 10-15, and 30-35 s after the onset of exercise. Cardiovascular responses to neck suction during cycling were compared with those obtained at rest. An attenuated reflex decrease in heart rate following neck suction was detected during moderate-intensity exercise, compared with the response at rest (P < 0.05). Furthermore, compared with the reflex decrease in blood pressure elicited at rest, neck suction elicited an augmented decrease in blood pressure at 0-5 and 10-15 s during low-intensity exercise and in all periods during moderate-intensity exercise (P < 0.05). The reflex depressor response at the onset of cycling was primarily mediated by an increase in the total vascular conductance. These findings evidence altered carotid baroreflex function during the first 35 s of cycling compared with rest, with attenuated bradycardic response, and augmented depressor response to carotid baroreceptor stimulation.

Muscle oxygen saturation increases during head‐up tilt induced (pre)syncope

To evaluate whether muscle vasodilatation plays a role for hypotension developed during central hypovolaemia, muscle oxygenation (SmO2) was examined during (pre)syncope induced by head‐up tilt (HUT). Skin blood flow (SkBF) and oxygenation (SskinO2) were determined because evaluation of SmO2 may be affected by superficial tissue oxygenation. Furthermore, we evaluated cerebral oxygenation (ScO2) and middle cerebral artery mean blood flow velocity (MCAvmean).

Sodium nitroprusside dilates cerebral vessels and enhances internal carotid artery flow in young men

Sodium nitroprusside lowers blood pressure by vasodilatation but is reported to reduce cerebral blood flow. In healthy young men sodium nitroprusside reduced blood pressure, total peripheral resistance, and arterial CO2 tension and yet cerebral blood flow was maintained, with an increase in internal carotid artery blood flow and cerebrovascular conductance. Sodium nitroprusside induces both systemic and cerebral vasodilatation affecting internal carotid artery more than vertebral artery flow.

Elevated Renal Oxygen Extraction During Open Abdominal Aortic Aneurysm Repair Is Related to Postoperative Renal Dysfunction

Background. Open abdominal aortic aneurysm repair is often followed by elevated plasma creatinine, likely due to impaired renal blood flow. We evaluated whether postoperative elevation in creatinine relates to renal oxygen extraction during surgery as an index of renal blood flow and also monitored frontal lobe oxygenation. Methods. For 19 patients (66 ± 10 years; mean ± SD) undergoing open infrarenal abdominal aortic aneurysm repair, renal oxygen extraction was determined by arterial and renal vein catheterization. Near-infrared spectroscopy determined frontal lobe oxygenation. Results. During surgery mean arterial pressure (from 102 ± 14 to 65 ± 11 mm Hg; P < .0001), arterial hemoglobin (from 7.7 ± 0.7 to 6.6 ± 0.8 mmol/L; P < 0.0001), and frontal lobe oxygenation (from 74 ± 6% to 70 ± 6%; P = .0414) decreased, while renal oxygen extraction increased (from 5.3% [4.3-8.1]; median [interquartile range] to 10.8% [5.8-17.5]; P = .0405). Plasma creatinine became significantly elevated on the second day after the operation (from 83 [73-101] to 105 µmol/L [79-143]; P = .0062) with a peak increase observed after 2 days (1-2). The peak increase in creatinine correlated to intraoperative renal oxygen extraction (r = 0.51; P = .026). Conclusion. Kidney function was affected after open abdominal aortic aneurysm repair likely related to limited renal blood flow. We take the increase in renal oxygen extraction and reduction in frontal lobe oxygenation to suggest that mean arterial pressure and hemoglobin were too low to maintain renal and cerebral circulation in vascular surgical patients.