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

Vascular uptake of rehydration fluids in hypohydrated men at rest and exercise

The purpose of this study was to formulate and to evaluate rehydration drinks, which would restore total body water and plasma volume (PV), for astronauts to consume before and during extravehicular activity, a few hours before reentry, and immediately after landing. In the first experiment (rest, sitting), five healthy men (23-41 yr), previously dehydrated for 24 hr., drank six (1a, 2, 4, 5, 6, 7) fluid formulations (one each at weekly intervals) and then sat for 70 min. Pre-test PV were measured with Evans blue dye and changes in PV were calculated with the hematocrit-hemoglobin transformation equation. This rest experiment simulated hypohydrated astronauts preparing for reentry. The second experiment (exercise, supine) followed the same protocol except four healthy men (30-46 yr) worked for 70 min. in the supine position on a cycle ergometer at a mean load of 71+/-1 percent of their peak aerobic work capacity. This exercise experiment simulated conditions for astronauts with reduced total body water engaging in extravehicular activity

Thoracic Impedance as a Potential Indicator of Gz-induced Presyncope

We investigated fluid shifts and regulatory responses to variations of posture, exercise, Gz level and radius of rotation in subjects riding NASA Ames 20G centrifuge. Results are from 4 protocols that address radius and exercise effects only. Protocol A: After 10 min supine control, 12 healthy men (35 9 yr, 82.8 7.9 kg) were exposed to rotational 1 Gz (2.5 m radius) for 2 min followed by 20 min alternating between 1 and 1.25 Gz. Blood samples were taken pre and post spin. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 8.3 m. Protocol D: Same as B but at 8.3 m. The 8 subjects who completed all protocols, increased heart rate (HR) from control by: A: 5, B: 39, C: 11, D: 44 bpm; and the 4 who did not: A: 6, B: 35, C: 20, D: 50 bpm. For thoracic fluid volume, (bioimpedance), the 8 subjects changed from control: A: -394, B: -548, C: -537, D: -708 mL; and the 4: A: -516, B: -652, C: -583, D: -1263 mL. The 4 subjects lost more thoracic fluid volume than the 8, especially in protocol D. A slightly greater increase in HR for the 4 compared to the 8 was not adequate to maintain cardiac output during D. Our data support the concept that thoracic impedance can detect inability to return adequate fluid to the heart, thereby predicting presyncope

Exercise exacerbates acute mountain sickness at simulated high altitude

We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, ~4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (V̇E), pulmonary function, arterial oxygen saturation (Sa(O2)), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 ± 1.0 and 1.3 ± 0.4 in Ex and Sed, respectively (P < 0.01); but resting V̇E and Sa(O2) were not different between trials. However, Sa(O2) during the exercise bouts in Ex was at 76.3 ± 1.7%, lower than during either Sed or at rest in Ex (81.4 ± 1.8 and 82.2 ± 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors