Circulating Plasma Oxytocin Level Is Elevated by High-Intensity Interval Exercise in Men.

PURPOSE: We evaluated whether repeated high-intensity interval exercise (HIIE) influences plasma oxytocin (OT) concentration in healthy men, and, given that OT is mainly synthesized in the hypothalamus, we assessed the concentration difference between the arterial (OT ART ) versus the internal jugular venous OT concentration (OT IJV ). Additionally, we hypothesized that an increase in cerebral OT release and the circulating concentration would be augmented by repeated HIIE. METHODS: Fourteen healthy men (age = 24 ± 2 yr; mean ± SD) performed two identical bouts of HIIE. These HIIE bouts included a warm-up at 50%-60% maximal workload ( Wmax ) for 5 min followed by four bouts of exercise at 80%-90% Wmax for 4 min interspersed by exercise at 50%-60% Wmax for 3 min. The HIIE bouts were separated by 60 min of rest. OT was evaluated in blood through radial artery and internal jugular vein catheterization. RESULTS: Both HIIE bouts increased both OT ART (median [IQR], from 3.9 [3.4-5.4] to 5.3 [4.4-6.3] ng·mL -1 in the first HIIE, P < 0.01) and OT IJV (from 4.6 [3.4-4.8] to 5.9 [4.3-8.2] ng·mL -1 , P < 0.01), but OT ART-IJV was unaffected (from -0.24 [-1.16 to 1.08] to 0.04 [-0.88 to 0.78] ng·mL -1 , P = 1.00). The increased OT levels were similar in the first and second HIIE bouts (OT ARTP = 0.25, OT IJVP = 0.36). CONCLUSIONS: Despite no change in the cerebral OT release via the internal jugular vein, circulating OT increases during HIIE regardless of the accumulated exercise volume, indicating that OT may play role as one of the exerkines.

Improved metabolic fitness, but no cardiovascular health effects, of a low-frequency short-term combined exercise programme in 50-70-year-olds with low fitness: A randomized controlled trial.

We evaluated the cardiometabolic effects of a 15-week combined exercise programme, implemented in sports clubs, for 50-70-year-olds with low aerobic fitness. In a randomized controlled trial, 45 participants (26 women) with low fitness were randomly assigned (2:1-ratio) to a training group (TG, n = 30) or inactive control group (CG, n = 15). TG had 15 weeks with one weekly 90-min supervised group-based session in a recreational sports club with combined aerobic exercise and strength training and were encouraged to perform home-based training 30 min/wk. Evaluations of relative VO2max (mLO2/min/kg), blood pressure, resting heart rate (HR), echocardiography, peripheral arterial tonometry, body composition, lipid profile and HbA1c were performed at 0 and 15 wks. Average HR during supervised training was 113 ± 13 bpm (68.6 ± 7.0%HRmax), with 4.3 ± 6.6% spent >90%HRmax. At 15-wk follow-up, intention-to-treat analyses revealed no between-group difference for VO2max/kg (0.4 mLO2/min/kg, 95%CI -0.8-1.5, P = 0.519; -3 mL/min, 95%CI -123-118, P = 0.966) or other cardiovascular outcomes (all P > 0.05). Compared to CG, total fat mass (-1.9 kg; 95%CI -3.2 to -0.5, P = 0.005), total fat percentage (-1.3%, 95%CI -2.2 to -0.3, P = 0.01) and total/HDL cholesterol ratio (P = 0.032) decreased in TG. Regular adherence to supervised training was high (81%), but 0% for home-based exercise. In conclusion, the group-based supervised training was associated with high adherence and moderate exercise intensity, whereas insufficiently supported home-based training was not feasible. Together, 15 wks of combined exercise training did not improve aerobic fitness or affected cardiovascular function in 50-70-yr-olds with low aerobic fitness, whereas some positive effects were observed in metabolic parameters.Highlights Combined exercise training implemented in a sports club elicited moderate aerobic intensity in 50-70-year-old untrained individuals.Supervised group-based training had high adherence whereas unsupported home-based training had very low adherence.15 weeks of low-frequency combined moderate intensity exercise training improved lipid profile and fat mass, but had no effect on cardiovascular fitness.

Influence of blood pressure on internal carotid artery blood flow during combined propofol-remifentanil and thoracic epidural anesthesia.

Background and Aims: Anesthesia often reduces mean arterial pressure (MAP) to a level that may compromise cerebral blood flow. We evaluated whether phenylephrine treatment of anesthesia-induced hypotension affects internal carotid artery (ICA) blood flow and whether anesthesia affects ICA flow and CO2 reactivity. Material and Methods: The study included twenty-seven patients (65 ± 11 years; mean ± SD) undergoing esophageal resection (n = 14), stomach resection (n = 12), or a gastroentero anastomosis (n = 1) during combined propofol-remifentanil and thoracic epidural anesthesia. Duplex ultrasound evaluated ICA blood flow. Evaluations were before and after induction of anesthesia, before and after the administration of phenylephrine as part of standard care to treat anesthesia-induced hypotension at a MAP below 60 mmHg, and the hypocapnic reactivity of ICA flow was determined before and during anesthesia. Results: Induction of anesthesia reduced MAP from 108 ± 12 to 66 ± 16 mmHg (P < 0.0001) and ICA flow from 340 ± 92 to 196 ± 52 mL/min (P < 0.0001). Phenylephrine was administered to 24 patients (0.1-0.2 mg) and elevated MAP from 53 ± 8 to 73 ± 8 mmHg (P = 0.0001) and ICA flow from 191 ± 43 to 218 ± 50 mL/min (P = 0.0276). Furthermore, anesthesia reduced the hypocapnic reactivity of ICA flow from 23 (18-33) to 14%/kPa (10-22; P = 0.0068). Conclusion: Combined propofol-remifentanil and thoracic epidural anesthesia affect ICA flow and CO2 reactivity. Phenylephrine partly restored ICA flow indicating that anesthesia-induced hypotension contributes to the reduction in ICA flow.

Randomized blinded trial of automated REBOA during CPR in a porcine model of cardiac arrest.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) reportedly elevates arterial blood pressure (ABP) during non-traumatic cardiac arrest. OBJECTIVES: This randomized, blinded trial of cardiac arrest in pigs evaluated the effect of automated REBOA two minutes after balloon inflation on ABP (primary endpoint) as well as arterial blood gas values and markers of cerebral haemodynamics and metabolism. METHODS: Twenty anesthetized pigs were randomized to REBOA inflation or sham-inflation (n = 10 in each group) followed by insertion of invasive monitoring and a novel, automated REBOA catheter (NEURESCUE® Catheter & NEURESCUE® Assistant). Cardiac arrest was induced by ventricular pacing. Cardiopulmonary resuscitation was initiated three min after cardiac arrest, and the automated REBOA was inflated or sham-inflated (blinded to the investigators) five min after cardiac arrest. RESULTS: In the inflation compared to the sham group, mean ABP above the REBOA balloon after inflation was higher (inflation: 54 (95%CI: 43-65) mmHg; sham: 44 (33-55) mmHg; P = 0.06), and diastolic ABP was higher (inflation: 38 (29-47) mmHg; sham: 26 (20-33) mmHg; P = 0.02), and the arterial to jugular oxygen content difference was lower (P = 0.04). After return of spontaneous circulation, mean ABP (inflation: 111 (95%CI: 94-128) mmHg; sham: 94 (95%CI: 65-123) mmHg; P = 0.04), diastolic ABP (inflation: 95 (95%CI: 78-113) mmHg; sham: 78 (95%CI: 50-105) mmHg; P = 0.02), CPP (P = 0.01), and brain tissue oxygen tension (inflation: 315 (95%CI: 139-491)% of baseline; sham: 204 (95%CI: 75-333)%; P = 0.04) were higher in the inflation compared to the sham group. CONCLUSION: Inflation of REBOA in a porcine model of non-traumatic cardiac arrest improves central diastolic arterial pressure as a surrogate marker of coronary artery pressure, and cerebral perfusion. INSTITUTIONAL PROTOCOL NUMBER: 2017-15-0201-01371.

Internal carotid artery blood flow is enhanced by elevating blood pressure during combined propofol-remifentanil and thoracic epidural anaesthesia: A randomised cross-over trial.

BACKGROUND: Anaesthesia reduces mean arterial pressure (MAP), and to preserve organ perfusion, vasopressors are often used to maintain MAP above 60 mmHg. Cognitive dysfunction is common following major surgery and may relate to intra-operative cerebral hypoperfusion. OBJECTIVE: The aim of this study was to evaluate whether internal carotid artery (ICA) blood flow increases when MAP is kept higher than 60 mmHg using noradrenaline. DESIGN: A randomised, cross-over trial. SETTING: Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark, from December 2017 to April 2018. PATIENTS: Patients with median [IQR] age 71 [63 to 75] years underwent pancreaticoduodenectomy (n = 19), total pancreatic resection (n = 1) or gastro-entero anastomosis (n = 2) during combined propofol-remifentanil and thoracic epidural anaesthesia. INTERVENTION: MAP was maintained between 60 to 65, 70 to 75 and 80 to 85 mmHg, in a random order, by noradrenaline infusion at a stable level of anaesthesia. MAIN OUTCOME MEASURES: Primary outcome was change in ICA flow at MAP 60 to 65 vs. 80 to 85 mmHg. Secondary outcomes were change in ICA flow at MAP 60 to 65 vs. 70 to 75 and 70 to 75 vs. 80 to 85 mmHg. Duplex ultrasound evaluated ICA flow. RESULTS: A (mean ± SD) increase in MAP from 62 ±â€Š1 to 82 ±â€Š1 mmHg elevated ICA flow from 196 ±â€Š53 to 226 ±â€Š61 ml min (mean difference 31 ml min; 95% CI 19 to 42; P < 0.0001). An increase in MAP from 62 ±â€Š1 to 72 ±â€Š1 mmHg elevated ICA flow to 210 ±â€Š52 ml min (P = 0.0271) and ICA flow increased further (P = 0.0165) when MAP was elevated to 82 ±â€Š1 mmHg. CONCLUSION: During combined propofol-remifentanil and thoracic epidural anaesthesia, ICA flow increased by approximately 15% when the MAP was elevated from about 60 to 80 mmHg. Treatment of a reduction in MAP brought about by anaesthesia seems to enhance ICA flow. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03309917.

The age-related reduction in cerebral blood flow affects vertebral artery more than internal carotid artery blood flow.

Ageing reduces cerebral blood flow (CBF), while mean arterial pressure (MAP) becomes elevated. According to 'the selfish brain' hypothesis of hypertension, a reduction in vertebral artery blood flow (VA) leads to increased sympathetic activity and thus increases MAP. In twenty-two young (24 ± 3 years; mean ± SD) and eleven elderly (70 ± 5 years) normotensive men, duplex ultrasound evaluated whether the age-related reduction in CBF affects VA more than internal carotid artery (ICA) blood flow. Pulse-contour analysis evaluated MAP while near-infrared spectroscopy determined frontal lobe oxygenation and transcranial Doppler middle cerebral artery mean blood velocity (MCA Vmean ). During supine rest, MAP (90 ± 13 versus 78 ± 9 mmHg; P<0·001) was elevated in the older subjects while their frontal lobe oxygenation (68 ± 7% versus 77 ± 7%; P<0·001), MCA Vmean (49 ± 9 versus 60 ± 12 cm s-1 ; P = 0·016) and CBF (754 ± 112 versus 900 ± 144 ml min-1 ; P = 0·004) were low reflected in VA (138 ± 48 versus 219 ± 50 ml min-1 ; P<0·001) rather than in ICA flow (616 ± 96 versus 680 ± 120 ml min-1 ; P = 0·099). In conclusion, blood supply to the brain and its oxygenation are affected by ageing and the age-related decline in VA flow appears to be four times as large as that in ICA and could be important for the age-related increase in MAP.

Dynamic Cerebral Autoregulation Is Maintained during High-Intensity Interval Exercise.

INTRODUCTION: High-intensity interval exercise (HIIE) is more effective at increasing metabolic and cardiovascular health compared with moderate-intensity continuous exercise for patients with cardiovascular disease, but exhaustive high-intensity continuous exercise attenuates dynamic cerebral autoregulation (CA). This study assessed the effect of HIIE on dynamic CA. METHODS: Nine healthy men (age, 24 ± 3 yr; mean ± SD) warmed up at 50%-60% maximal workload (Wmax) for 5 min before HIIE including four 4-min bouts of exercise at 80%-90% Wmax interspaced by four 3-min bouts at 50% to 60% Wmax. Transcranial Doppler determined middle cerebral artery mean blood velocity (MCA Vmean), and brachial artery catheterization determined mean arterial pressure (MAP). Dynamic CA was evaluated by transfer function analysis of changes in MAP and MCA Vmean. RESULTS: The HIIE increased MAP (from 92 ± 9 to 104 ± 10 mm Hg; P < 0.0125), whereas MCA Vmean did not change. Transfer function phase increased and coherence decreased during HIIE (P < 0.0125 vs rest, respectively), whereas gain was unchanged. CONCLUSIONS: The results suggest that dynamic CA is unaffected during HIIE, indicating that the brain is protected from fluctuations in MAP. Thus, we propose that HIIE may be beneficial for brain-related health as maintenance of cerebral perfusion in contrast to high-intensity continuous exercise.

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation during head-up tilt in men.

Phenylephrine is an α-adrenergic agent and yet seems to increase near-infrared spectroscopy determined muscle oxygenation (SmO2) that reflects the ratio between oxygenated (O2Hb) and deoxygenated (Hb) haemoglobin/myoglobin. We examined whether the increase in SmO2 by phenylephrine reflects veno-constriction and to secure filling of the veins, subjects were exposed to head-up tilt (HUT). Phenylephrine (0.2 mg) was administered to 10 healthy males (24 years (22-27; median with interquartile range)) during 40° HUT with SmO2, O2Hb and Hb determined for the biceps brachii and vastus lateralis muscles. Changes in red cell volume within the thorax and thigh were evaluated by electrical admittance and brachial vein diameter determined by ultrasound. HUT accumulated blood in arms and legs as indicated by reduced thoracic and conversely enhanced thigh electrical admittance. Both over the arm and leg, HUT reduced SmO2 as a consequence of reduced O2Hb and increased Hb (p < .05). After 5 min HUT, phenylephrine increased MAP and total peripheral resistance, and both arm and thigh SmO2 increased due to a decrease in Hb and an increase in O2Hb. The results confirm that SmO2 decreases during HUT and demonstrate venous filling in the limbs. Furthermore, vasoconstriction during HUT is indicated by a decrease in O2Hb. Conversely, phenylephrine increased SmO2 likely illustrating increased muscle blood flow and venoconstriction as O2Hb increased while Hb was reduced.

Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow.

Leg immersion in carbonated water improves endothelial-mediated vasodilator function and decreases arterial stiffness but the mechanism underlying this effect remains poorly defined. We hypothesized that carbonated water immersion increases muscle blood flow. To test this hypothesis, 10 men (age 21 ± 0 years; mean ± SD) underwent lower leg immersion in tap or carbonated water at 38°C. We evaluated gastrocnemius muscle oxyhemoglobin concentration and tissue oxygenation index using near-infrared spectroscopy, skin blood flow by laser Doppler flowmetry, and popliteal artery (PA) blood flow by duplex ultrasound. Immersion in carbonated, but not tap water elevated PA (from 38 ± 14 to 83 ± 31 mL/min; P < 0.001) and skin blood flow (by 779 ± 312%, P < 0.001). In contrast, lower leg immersion elevated oxyhemoglobin concentration and tissue oxygenation index with no effect of carbonation (P = 0.529 and P = 0.495). In addition, the change in PA blood flow in response to immersion in carbonated water correlated with those of skin blood flow (P = 0.005) but not oxyhemoglobin concentration (P = 0.765) and tissue oxygenation index (P = 0.136) while no relations was found for tap water immersion. These findings indicate that water carbonation has minimal effect on muscle blood flow. Furthermore, PA blood flow increases in response to lower leg immersion in carbonated water likely due to a large increase in skin blood flow.

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

KEY POINTS: 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. ABSTRACT: Cerebral autoregulation maintains cerebral blood flow (CBF) despite marked changes in mean arterial pressure (MAP). Sodium nitroprusside (SNP) reduces blood pressure by vasodilatation but is reported to lower CBF, probably by a reduction in its perfusion pressure. We evaluated the influence of SNP on CBF and aimed for a 20% and then 40% reduction in MAP, while keeping MAP ≥ 50 mmHg, to challenge cerebral autoregulation. In 19 healthy men (age 24 ± 4 years; mean ± SD) duplex ultrasound determined right internal carotid (ICA) and vertebral artery (VA) blood flow. The SNP reduced MAP (from 83 ± 8 to 69 ± 8 and 58 ± 4 mmHg; both P < 0.0001), total peripheral resistance, and arterial CO2 tension (P aC O2; 41 ± 3 vs. 39 ± 3 and 37 ± 4 mmHg; both P < 0.01). Yet ICA flow increased with the moderate reduction in MAP but returned to the baseline value with the large reduction in MAP (336 ± 66 vs. 365 ± 69; P = 0.013 and 349 ± 82 ml min-1 ; n.s.), while VA flow (114 ± 34 vs. 112 ± 38 and 110 ± 42 ml min-1 ; both n.s.) and CBF ((ICA + VA flow) × 2; 899 ± 135 vs. 962 ± 127 and 918 ± 197 ml min-1 ; both n.s.) were maintained with increased cerebrovascular conductance. In conclusion, CBF is maintained during SNP-induced reduction in MAP despite reduced P aC O2 and the results indicate that SNP dilates cerebral vessels and increases ICA flow.

A mesenteric traction syndrome affects near-infrared spectroscopy evaluated cerebral oxygenation because skin blood flow increases.

During abdominal surgery manipulation of internal organs may induce a "mesenteric traction syndrome" (MTS) including a triad of flushing, hypotension, and tachycardia that lasts for about 30 min. We evaluated whether MTS affects near-infrared spectroscopy (NIRS) assessed frontal lobe oxygenation (ScO2) by an increase in forehead skin blood flow (SkBF). The study intended to include 10 patients who developed MTS during pancreaticoduodenectomy and 22 patients were enrolled (age 61 ± 8 years; mean ± SD). NIRS determined ScO2, laser Doppler flowmetry determined SkBF, cardiac output (CO) was evaluated by pulse-contour analysis (Modelflow), and transcranial Doppler assessed middle cerebral artery mean flow velocity (MCA Vmean). MTS was identified by flushing within 60 min after start of surgery. MTS developed 20 min (12-24; median with range) after the start of surgery and heart rate (78 ± 16 vs. 68 ± 17 bpm; P = 0.0032), CO (6.2 ± 1.4 vs. 5.3 ± 1.1 L min-1; P = 0.0086), SkBF (98 ± 35 vs. 80 ± 23 PU; P = 0.0271), and ScO2 (71 ± 6 vs. 67 ± 8%; P < 0.0001), but not MCA Vmean (32 ± 8 vs. 32 ± 7; P = 0.1881) were largest in the patients who developed MTS. In some patients undergoing abdominal surgery NIRS-determined ScO2 is at least temporarily affected by an increase in extra-cranial perfusion independent of cerebral blood flow as indicated by MCA Vmean. Thus, NIRS evaluation of ScO2 may overestimate cerebral oxygenation if patients flush during surgery.

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 repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake. 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.

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.

ADRB2 gly16gly Genotype, Cardiac Output, and Cerebral Oxygenation in Patients Undergoing Anesthesia for Abdominal Aortic Aneurysm Surgery.

BACKGROUND: Gly16arg polymorphism of the adrenergic ß2-receptor is associated with the elevated cardiac output (Q) in healthy gly16-homozygotic subjects. We questioned whether this polymorphism also affects Q and regional cerebral oxygen saturation (SCO2) during anesthesia in vascular surgical patients. METHODS: One hundred sixty-eight patients (age 71 ± 6 years) admitted for elective surgery were included. Cardiovascular variables were determined before and during anesthesia by intravascular pulse contour analysis (Nexfin) and SCO2 by cerebral oximetry (INVOS 5100C). Genotyping was performed with the TaqMan assay. RESULTS: Before anesthesia, Q and SCO2 were 4.7 ± 1.2 L/min and 66% ± 8%, respectively, and linearly correlated (r = 0.35, P < .0001). In patients with the gly16gly genotype baseline, Q was approximately 0.4 L/min greater than in arg16 carriers (CI95: 0.0-0.8, Pt test = .03), but during anesthesia, the difference was 0.3 L/min (Pmixed-model = .07). Post hoc analysis revealed the change in SCO2 from baseline to the induction of anesthesia to be on average 2% greater in gly16gly homozygotes than in arg16 patients when adjusted for the change in Q (P = .03; CI95: 0.2-4.0%). CONCLUSIONS: This study suggests that the ß2-adrenoceptor gly16gly genotype is associated with the elevated resting Q. An interesting trend to greater frontal lobe oxygenation at induction of anesthesia in patients with gly16gly genotype was found, but because of insufficient sample size and lack of PCO2 control throughout the measurements, the presented data may only serve as the hypothesis generating for future studies. The confidence limits indicate that the magnitude of the effects may range from clinically insignificant to potentially important.

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.

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.

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

We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% Wmax), high (75% W(max)) and exhaustive (100% W(max)) workloads. Mean middle cerebral artery blood velocity (MCA V(mean)), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide (P(aCO2)) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O2), glucose and lactate across the brain. The molar ratio between cerebral uptake of O2 versus carbohydrate (O2-carbohydrate index; O2/[glucose + 1/2 lactate]; OCI), the cerebral metabolic rate of O2 (CMRO2) and changes in mitochondrial O2 tension ( P(mitoO2)) were calculated. 100% W(max) was ~33% lower in the older group. Exercise increased MAP and CO in both groups (P < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA V(mean), P(aCO2) and cerebral vascular conductance index (MCA V(mean)/MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO2 (by ~30 µmol (100 g(-1)) min(-1)), and decreases in OCI (by ~1.5) and (by ~10 mmHg) during exercise at 75% W(max). Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals.