Lonnie G. Petersen

Vasorelaxation in space

During everyday life, gravity constantly stresses the cardiovascular system in upright humans by diminishing venous return. This decreases cardiac output and induces systemic vasoconstriction to prevent blood pressure from falling. We therefore tested the hypothesis that entering weightlessness leads to a prompt increase in cardiac output and to systemic vasodilatation and that these effects persist for at least a week of weightlessness in space. Cardiac output and mean arterial pressure were measured in 8 healthy humans during acute 20-s periods of weightlessness in parabolic airplane flights and on the seventh and eighth day of weightlessness in 4 astronauts in space. The seated 1-G position acted as reference. Entering weightlessness promptly increased cardiac output by 29±7%, from 6.6±0.7 to 8.4±0.9 L min−1 (mean±SEM; P=0.003), whereas mean arterial pressure and heart rate were unaffected. Thus, systemic vascular resistance decreased by 24±4% (P=0.017). After a week of weightlessness in space, cardiac output was increased by 22±8% from 5.1±0.3 to 6.1±0.1 L min−1 (P=0.021), with mean arterial pressure and heart rate being unchanged so that systemic vascular resistance was decreased by 14±9% (P=0.047). In conclusion, entering weightlessness promptly increases cardiac output and dilates the systemic circulation. This vasorelaxation persists for at least a week into spaceflight. Thus, it is probably healthy for the human cardiovascular system to fly in space.

Effect of gravity and microgravity on intracranial pressure

Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.

Effect of postural changes on ICP in healthy and ill subjects

BackgroundReference values and physiological measurements of intracranial pressure (ICP) are primarily reported in the supine position, while reports of ICP in the vertical position are surprisingly rare considering that humans maintain the vertical position for the majority of the day. In order to distinguish normal human physiology from disease entities such as idiopathic intracranial hypertension and normal pressure hydrocephalus, we investigated ICP in different body postures in both normal and ill subjects.MethodsThirty-one patients were included: four normal patients following complete removal of a solitary clearly demarcated small brain tumour and fitted with a telemetric ICP monitoring device for long-term ICP monitoring; 27 patients requiring invasive ICP monitoring as a part of their diagnostic work-up or monitoring of shunt treatment effect. ICP was recorded in the following body positions: upright standing, sitting in a chair, supine and right lateral lumbar puncture position.ResultsLinear regression of median ICP based on patient posture, group, and purpose of monitoring presented a significant model (p < 0.001), but could not distinguish between patient groups (p = 0.88). Regression of differences in median ICP between body postures and supine ICP as the baseline, presented a highly significant model (p < 0.001) and adjusted R2 = 0.86. Both body posture (p < 0.001) and patient group (p < 0.001) were highly significant factors.ConclusionsDifferences in ICP between body postures enabled us to distinguish the normal group from patient groups. Normal patients appear able to more tightly regulate ICP when switching body postures.

Mechanisms of increase in cardiac output during acute weightlessness in humans

Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.

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

The hydrostatic pressure indifference point underestimates orthostatic redistribution of blood in humans

The hydrostatic indifference point (HIP; where venous pressure is unaffected by posture) is located at the level of the diaphragm and is believed to indicate the orthostatic redistribution of blood, but it remains unknown whether HIP coincides with the indifference point for blood volume (VIP). During graded (± 20°) head-up (HUT) and head-down tilt (HDT) in 12 male volunteers, we determined HIP from central venous pressure and VIP from redistribution of both blood, using ultrasound imaging of the inferior caval vein (VIPui), and fluid volume, by regional electrical admittance (VIPadm). Furthermore, we evaluated whether inflation of medical antishock trousers (to 70 mmHg) affected HIP and VIP. Leaving cardiovascular variables unaffected by tilt, HIP was located 7 ± 4 cm (mean ± SD) below the 4th intercostal space (IC-4) during HUT and was similar (7 ± 3 cm) during HDT and higher (P < 0.0001) than both VIPui (HUT: 22 ± 16 cm; HDT: 13 ± 7 cm) and VIPadm (HUT: 29 ± 9 cm; HDT: 20 ± 9 cm below IC-4). During HUT antishock trousers elevated both HIP and VIPui [to 3 ± 5 cm (P = 0.028) and 17 ± 7 cm below IC-4 (P = 0.051), respectively], while VIPadm remained unaffected. By simultaneous recording of pressure and filling of the inferior caval vein as well as fluid distribution, we found HIP located corresponding to the diaphragm while VIP was placed low in the abdomen, and that medical antishock trousers elevated both HIP and VIP. The low indifference point for volume shows that the gravitational influence on distribution of blood is more profound than indicated by the indifference point for venous pressure.

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.

Body height and arterial pressure in seated and supine young males during +2 G centrifugation

It is known that arterial pressure correlates positively with body height in males, and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore, we tested the hypothesis that a higher gravito-inertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162-171 cm; n = 8) and tall (194-203 cm; n = 10) healthy males (18-41 yr), brachial arterial pressure, heart rate (HR), and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22 ± 2 mmHg, P < 0.0001) and tall (23 ± 2 mmHg, P < 0.0001) males, with no significant difference between the groups. HR increased more (P < 0.05) in the tall than in the short group (14 ± 2 vs. 7 ± 2 bpm). Stroke volume (SV) decreased in the short group (26 ± 4 ml, P = 0.001) and more so in the tall group (39 ± 5 ml, P < 0.0001; short vs. tall, P = 0.047). During +2Gx, systolic arterial pressure increased (P < 0.001) and SV (P = 0.012) decreased in the tall group only. In conclusion, during +2Gz, MAP increased in both short and tall males, with no difference between the groups. However, in the tall group, HR increased more during +2Gz, which could be caused by a larger hydrostatic pressure gradient from heart to head, leading to greater inhibition of the carotid baroreceptors.

The Gly16 Allele of the G16R Single Nucleotide Polymorphism in the β2-Adrenergic Receptor Gene Augments the Glycemic Response to Adrenaline in Humans

Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G > A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Forty healthy Caucasian men were included from a group of genotyped individuals. Cardio- and cerebrovascular variables at baseline and during a 60-min adrenaline infusion (0.06 μg kg−1 min−1) were measured by Model flow, near-infrared spectroscopy and transcranial Doppler sonography. Blood samples were obtained from an artery and a retrograde catheter in the right internal jugular vein. The ADRB2 G16R variation had no effect on baseline arterial glucose, but during adrenaline infusion plasma glucose was up to 1.2 mM (CI95: 0.36–2.1, P < 0.026) higher in the Gly16 homozygotes compared with Arg16 homozygotes. The extrapolated steady-state levels of plasma glucose was 1.9 mM (CI95: 1.0 –2.9, PNLME < 0.0026) higher in the Gly16 homozygotes compared with Arg16 homozygotes. There was no change in the cerebral oxygen glucose index and the oxygen carbohydrate index during adrenaline infusion and the two indexes were not affected by G16R polymorphism. No difference between genotype groups was found in cardiac output at baseline or during adrenaline infusion. The metabolic response of glucose during adrenergic stimulation with adrenaline is associated to the G16R polymorphism of ADRB2, although without effect on cerebral metabolism. The differences in adrenaline-induced blood glucose increase between genotypes suggest an elevated β2-adrenergic response in the Gly16 homozygotes with increased adrenaline-induced glycolysis compared to Arg16 homozygotes.