Schneditz D. Reactive hyperemia in the human liver

We tested whether hepatic blood flow is altered following central hypovolemia caused by simulated orthostatic stress. After 30 min of supine rest, hemodynamic, plasma density, and indocyanine green (ICG) clearance responses were determined during and after release of a 15-min 40 mmHg lower body negative pressure (LBNP) stimulus. Plasma density shifts and the time course of plasma ICG concentration were used to assess intravascular volume and hepatic perfusion changes. Plasma volume decreased during LBNP (Ϫ10%) as did cardiac output (Ϫ15%), whereas heart rate (ϩ14%) and peripheral resistance (ϩ17%) increased, as expected. On the basis of ICG elimination, hepatic perfusion decreased from 1.67 Ϯ 0.32 (pre-LBNP control) to 1.29 Ϯ 0.26 l/min (Ϫ22%) during LBNP. Immediately after LBNP release, we found hepatic perfusion 25% above control levels (to 2.08 Ϯ 0.48 l/min, P ϭ 0.0001). Hepatic vascular conductance after LBNP was also significantly higher than during pre-LBNP control (21.4 Ϯ 5.4 vs. 17.1 Ϯ 3.1 ml ⅐ min Ϫ1 ⅐ mmHg Ϫ1 , P Ͻ 0.0001). This indicates autoregulatory vasodilatation in response to relative ischemia during a stimulus that has cardiovascular effects similar to normal orthostasis. We present evidence for physiological post-LBNP reactive hyperemia in the human liver. Further studies are needed to quantify the intensity of this response in relation to stimulus duration and magnitude, and clarify its mechanism. hepatic; indocyanine green; orthostasis; splanchnic blood flow; autoregulation; lower body negative pressure CENTRAL HYPOVOLEMIA, AS CAUSED by blood redistribution (e.g., orthostasis) or blood loss (e.g., trauma) can be simulated by application of negative pressure to the body from the iliac crest downward (lower body "negative" pressure, LBNP), as this leads to peripheral blood pooling while avoiding additional hydrostatic effects of upright posture (14). Driven by decreased load on cardiopulmonary and eventually arterial baroreceptors, neurohumoral readjustments occur. The splanchnic vascular bed is a major regulatory target because it represents a large regional vascular conductance and constitutes the primary blood reserve in cardiovascular "emergency" situations (11) Even low (Յ20 mmHg) levels of LBNP suffice to induce sympathetic activation and reduce splanchnic perfusion (17), whereas higher stimulus levels (e.g., 50 mmHg) lower splanchnic vascular conductance as well, by as much as Ϸ30% (6, 33). Reduced perfusion has local metabolic consequences. Vascular "escape" from sympathetic influence (9, 34) and the general concept of "reactive hyperemia" (20, 31) and autoregulation (38) are well established, but hepatic reactive hyperemia as such has not yet been reported. Splanchnic ischemia is connected to hypotensive episodes especially under prolonged hypovolemic stress such as hemodialysis and ultrafiltration of excess body fluid (12, 36). We speculated whether a much shorter perturbation such as standard LBNP would also induce ischemia. We measured hepatic clearance of ICG as a surrogate for splanchnic perfusion before, during, and after LBNP and hypothesized that after LBNP-induced vasoconstriction, hepatic perfusion would not only return to but also actually exceed pre-LBNP control levels, owing to local effects of relative hypoperfusion induced metabolite accumulation that occurred during LBNP. METHODS The study was done in 14 healthy, male volunteers of moderate physical fitness, free from cardiovascular, renal, hepatic, and pulmonary diseases and not on any medication. The subjects abstained from use of tobacco, caffeine, alcohol, and heavy exercise for at least 48 h preceding each investigation and the subjects were their own controls. The Graz Medical University Research Ethics Committee approved the study protocol, and written, informed consent was obtained from each subject. Before the study, LBNP sham runs without blood sampling were carried out for familiarization to the study (24). Protocols were conducted between 9 and 12 AM to minimize circadian influences on hemodynamic variables (29). The subjects were fasting and emptied the bladder before each study. An antecubital vein was cannulated, for blood sampling and administration of ICG. Experiments were carried out in a semidark, quiet room maintained at 24°C and humidity at 55%. A padded pair of tightly connected chains was used to stabilize and maintain an exact sealing position at the exact level of the iliac crest within the LBNP box (14). The box was equipped with a footrest that was individually adjusted before LBNP was commenced. A pillow supported the head to avoid stimulation of the otolith organs, which has been reported to increase muscle sympathetic nerve activity and calf vascular resistance (21). Baseline data were collected for 30 min in the supine position, with the seal in place, before LBNP to allow for reequilibration of gravityrelated fluid shifts (16). Pressure within the box was lowered electronically by a pump within 10 s and monitored by an electronic gauge (24). LBNP (Ϫ40 mmHg) lasted for 15 min because any longer period affects LBNP tolerance (15). During LBNP the subjects were instructed to avoid movements of the lower limbs and to breathe normally. The post-LBNP observation period lasted another 15 min. The time course of the experimental protocol is shown in Blood volume and hepatic perfusion. ICG (25 mg) was injected at two times, 20 min before and 7 min into LBNP, with sufficient time between injections for ICG to be completely cleared from the blood stream. Whereas the ICG disappearance following the first injectio

From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006)

Bed rest studies of the past 20 years are reviewed. Head-down bed rest (HDBR) has proved its usefulness as a reliable simulation model for the most physiological effects of spaceflight. As well as continuing to search for better understanding of the physiological changes induced, these studies focused mostly on identifying effective countermeasures with encouraging but limited success. HDBR is characterised by immobilization, inactivity, confinement and elimination of Gz gravitational stimuli, such as posture change and direction, which affect body sensors and responses. These induce upward fluid shift, unloading the body’s upright weight, absence of work against gravity, reduced energy requirements and reduction in overall sensory stimulation. The upward fluid shift by acting on central volume receptors induces a 10–15% reduction in plasma volume which leads to a now well-documented set of cardiovascular changes including changes in cardiac performance and baroreflex sensitivity that are identical to those in space. Calcium excretion is increased from the beginning of bed rest leading to a sustained negative calcium balance. Calcium absorption is reduced. Body weight, muscle mass, muscle strength is reduced, as is the resistance of muscle to insulin. Bone density, stiffness of bones of the lower limbs and spinal cord and bone architecture are altered. Circadian rhythms may shift and are dampened. Ways to improve the process of evaluating countermeasures—exercise (aerobic, resistive, vibration), nutritional and pharmacological—are proposed. Artificial gravity requires systematic evaluation. This review points to clinical applications of BR research revealing the crucial role of gravity to health