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Biomedical subjects

Donald S Prough

Publications and source records attributed to Donald S Prough.

At least 19 recordsLinked to original sources
PubMed2006

Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury.

Hippocampal damage contributes to cognitive dysfunction after traumatic brain injury (TBI). We previously showed that Fluoro-Jade, a fluorescent stain that labels injured, degenerating brain neurons, quantifies the extent of hippocampal injury after experimental fluid percussion TBI in rats. Coincidentally, we observed that injured neurons in the rat hippocampus also stained with Newport Green, a fluorescent dye specific for free ionic zinc. Here, we show that, regardless of injury severity or therapeutic intervention, the post-TBI population of injured neurons in rat hippocampal subfields CA1, CA3 and dentate gyrus is indistinguishable, both in numbers and anatomical distribution, from the population of neurons containing high levels of zinc. Treatment with lamotrigine, which inhibits presynaptic release of glutamate and presumably zinc that is co-localized with glutamate, reduced numbers of Fluoro-Jade-positive and Newport Green-positive neurons equally as did treatment with nicardipine, which blocks voltage-gated calcium channels through which zinc enters neurons. To confirm using molecular techniques that Fluoro-Jade and Newport Green-positive neurons are equivalent populations, we isolated total RNA from 25 Fluoro-Jade-positive and 25 Newport Green-positive pyramidal neurons obtained by laser capture microdissection (LCM) from the CA3 subfield, linearly amplified the mRNA and used quantitative ribonuclease protection analysis to demonstrate similar expression of mRNA for selected TBI-induced genes. Our data suggest that therapeutic interventions aimed at reducing neurotoxic zinc levels after TBI may reduce hippocampal neuronal injury.

Animals↗
PubMed2006

Molecular correlates of age-specific responses to traumatic brain injury in mice.

Aged traumatic brain injury (TBI) patients suffer higher rates of mortality and disability than younger patients. Cognitive problems common to TBI patients are associated with damage to the hippocampus, a central locus of learning and memory. To investigate the molecular mechanisms of age-related vulnerability to brain injury in a mouse model of TBI, we studied the effects of TBI on hippocampal gene expression in young and aged mice. Young and aged male C57Bl/6 mice were subjected to sham injury or TBI and sacrificed 24 h post-injury. We used laser capture microdissection to obtain pure populations of neurons from the CA1, CA3, and dentate gyrus subfields of the hippocampus. We compared injury-induced gene expression in hippocampal neurons of young and aged mice using quantitative ribonuclease protection assay analysis of linearly amplified mRNA from laser captured neurons. Both increased age and TBI were associated with increased expression of neuroprotective (brain-derived neurotrophic factor), pro-inflammatory (interleukin-1beta), and proapoptotic (caspase-3) genes in mouse hippocampal neurons. Our data support previous reports that suggested the CA3 subregion is highly susceptible to fluid percussion TBI and that age-related changes in gene expression are one potential mechanism of increased vulnerability of the aged brain to TBI.

Aging↗
PubMed2006

Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury.

Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration.

Animals↗
PubMed2006

In vivo study of glucose-induced changes in skin properties assessed with optical coherence tomography.

Recently, our in vivo studies demonstrated a strong correlation between blood glucose concentration and the slope of the optical coherence tomography (OCT) signal when the probing beam was scanned over a straight line. To improve the sensitivity of OCT for blood glucose monitoring, two-dimensional (2D) lateral scanning of the OCT probing beam was proposed. Depth-dependent changes in pig skin properties with variation of blood glucose concentration were revealed due to significant suppression of speckle noise and motion artefacts in 2D scanning mode. The correlation coefficient of the OCT signal slope with blood glucose concentration varied periodically in the range from -0.9 to +0.9 depending on depth. The period of variation of the correlation coefficient was 100-150 microm that corresponded to the distance between neighbour collagen bundles. We also observed a decrease of skin thickness by 10 +/- 7.5 microm with an increase of blood glucose concentration by 277 +/- 56 mg dl(-1). Mechanisms of glucose-induced changes in skin properties owing to tissue layer shift caused by dehydration associated with the glucose osmotic effect were considered.

Animals↗
PubMed2006

Multiwavelength optoacoustic system for noninvasive monitoring of cerebral venous oxygenation: a pilot clinical test in the internal jugular vein.

A noninvasive, high-resolution optoacoustic technique is a promising alternative to currently used invasive methods of brain oxygenation monitoring. We present the results of our pilot clinical test of this technique in healthy volunteers. Multiwavelength optoacoustic measurements (with nanosecond optical parametric oscillator as a source of radiation) were performed on the area of the neck overlying the internal jugular vein, a deeply located large vein that drains blood from the brain and from extracranial tissues. Optoacoustic signals induced in venous blood were measured with high resolution and signal-to-noise ratio despite the presence of a thick layer of overlying tissue (up to 10 mm). The characteristic parameters of the signal at different wavelengths correlated well with the spectrum of the effective attenuation coefficient of blood.

Acoustics↗
PubMed2006

Splanchnic oxygen consumption is impaired during severe acute normovolemic anemia in anesthetized humans.

BACKGROUND: In conscious humans, reduction in hemoglobin concentration to 5 g/dl did not produce inadequate systemic oxygenation. However, systemic measures of inadequate oxygenation may not be sufficiently sensitive to detect inadequate oxygenation in individual organs such as splanchnic organs. The authors tested the hypothesis that acute normovolemic anemia to hemoglobin less than 6.0 g/dl in anesthetized humans reduces splanchnic oxygen consumption because of diminished whole body oxygen delivery. METHODS: Elective spine (n = 12) and abdominal (n = 7) surgery patients underwent acute normovolemic anemia to decrease the hemoglobin concentration close to 6.0 g/dl. The authors assessed the development of supply-dependent conditions in systemic and regional vascular beds by two primary measures before and after acute normovolemic anemia: oxygen consumption and surrogate biochemical markers of anaerobic metabolism, including plasma lactate, regional lactate kinetics, and ketone body ratio. RESULTS: When hemoglobin was reduced from 13.6 +/- 1.2 to 5.9 +/- 0.3 g/dl, oxygen supply dependency occurred in the splanchnic and preportal tissues but not at the systemic level. Regional supply dependency was accompanied by biochemical markers of anaerobic metabolism. CONCLUSIONS: In anesthetized humans, a reduction in hemoglobin to 5.9 g/dl by acute normovolemic anemia diminished splanchnic and preportal whole body oxygen delivery and impaired splanchnic and preportal oxygen consumption. This was accompanied by increased plasma levels of regional lactate and an increased beta-hydroxybutyrate-to-acetoacetate ratio. These findings suggest that the risk to the gastrointestinal tract during acute normovolemic anemia may be underestimated.

Adult↗
PubMed2006

Normotensive and hypotensive closed-loop resuscitation using 3.0% NaCl to treat multiple hemorrhages in sheep.

OBJECTIVE: NaCl solutions (7.5%) have been reported to be effective for resuscitation in animals and trauma patients, but these solutions are not approved for use in the United States. We hypothesized that infusion of Food and Drug Administration-approved 3% NaCl provides superior cardiovascular and metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage. Our objective was to compare four groups, hypotensive and normotensive resuscitation of hemorrhage using 3% NaCl (HS) or lactated Ringer's (LR). DESIGN: Sheep were hemorrhaged in three separate bleeds, 25 mL/kg at T0 mins and 5 mL/kg at both T50 and T70 mins. SETTING: University laboratory. SUBJECTS: Instrumented conscious sheep. INTERVENTIONS: Resuscitation was started at T30 mins and continued until T180. Normotensive and hypotensive resuscitation to mean arterial pressures of 90 mm Hg and 65 mm Hg, respectively, was performed with LR or HS using a closed-loop resuscitation system. MEASUREMENTS AND MAIN RESULTS: All four groups were successfully resuscitated to near target levels. Two animals in the hypotensive treatment protocols died during the second and third bleeding, one with the LR65 group and one with the HS65 group. Mean infused volumes were 59.9 +/- 7.0 and 18.0 +/- 5.9 in the LR90 and LR65 groups, respectively, and were 19.6 +/- 2.2 mL/kg and 13.3 +/- 5.7 mL/kg in the HS90 and HS65 treatments (p < .05; LR90 vs. each of the groups). Cardiac indexes were significantly higher with normotensive vs. hypotensive treatment. However, there was no hemodynamic advantage apparent with HS vs. LR when compared with the normotensive or hypotensive treatments. Some animals had high lactate levels (>10 mmol) with both of the hypotensive treatments and also with the HS90 treatment, while not one of the 11 LR90 treatment animals had lactate levels >8 mmol. CONCLUSIONS: Volume sparing was apparent with HS, but no hemodynamic or metabolic advantage was apparent when used for either normotensive or hypotensive resuscitation. Trends toward lower base excess values and higher occurrences of deaths only in the hypotensive treatment protocols suggest that resuscitation to a target mean arterial pressure of 65 mm Hg may be too low.

Animals↗
PubMed2006

Left ventricular diastolic filling characteristics are not impaired but systolic performance was augmented in the early hours of experimental endotoxemia in humans.

This study was performed to determine whether endotoxemia causes diastolic cardiac dysfunction. Eleven healthy volunteers, 30 +/- 6 years of age, underwent comprehensive transthoracic echocardiographic assessment including two-dimensional, M-mode transmitral and tissue Doppler of systolic and diastolic function at baseline and at 3 and 5 h after intravenous administration of purified Escherichia coli endotoxin (4 ng/kg). Data were analyzed by analysis of variance; P values of less than 0.05 were considered significant. Endotoxin administration resulted in a hyperdynamic state characterized by decreased mean arterial pressure and significant increase in cardiac index. This was accompanied by increases in several load-dependent systolic performance indices (3 and 5 h). Robust increases in peak systolic blood pressure/end-systolic volume index, one of the relatively load-independent contractility parameter, were also observed at 3 h after endotoxin administration. Transmitral peak early velocity (E), which represents early filling, significantly increased at 3 h after infusion. Late diastolic velocity (A), which represents atrial contraction, significantly increased at 3 and 5 h after infusion. The E/A ratio indicative of delayed relaxation significantly decreased due to increases in A (transmitral) and A (tissue Doppler) at 3 and 5 h after infusion. As expected, endotoxin infusion resulted in a hyperdynamic state associated with increases in systolic function indices including endocardial systolic velocities. The observed decreases in E/A (transmitral) and E/A (tissue Doppler) ratio were primarily due to increases in A and A. Moreover, isovolumic relaxation time and time constant for left ventricular relaxation, a load-independent parameter for ventricular relaxation, remained unchanged at 3 and 5 h after endotoxin infusion. Therefore, our findings are more likely due to enhanced atrial contractility resulting from increased sympathetic activity in response to reduction in left ventricular afterload and not due to altered diastolic filling characteristics.

Adult↗
PubMed2006

Effects of hypertonic arginine on cerebral blood flow and intracranial pressure after traumatic brain injury combined with hemorrhagic hypotension.

Hypertonic saline solutions improve cerebral blood flow (CBF) when used for acute resuscitation from hemorrhagic hypotension accompanying some models of traumatic brain injury (TBI); however, the duration of increased CBF is brief. Because the nitric oxide synthase substrate l-arginine provides prolonged improvement in CBF after TBI, we investigated whether a hypertonic resuscitation fluid containing l-arginine would improve CBF in comparison to hypertonic saline without l-arginine in a model of moderate, paramedian, fluid-percussion TBI followed immediately by hemorrhagic hypotension (mean arterial pressure [MAP] = 60 mm Hg for 45 min). Sprague-Dawley rats were anesthetized with 4.0% isoflurane, intubated and ventilated with 1.5%-2.0% isoflurane in oxygen/air (50:50). After preparation for TBI and measurement of CBF using laser Doppler flowmetry and measurement of intracranial pressure (ICP) using an implanted transducer, rats were subjected to moderate (2.0 atm) TBI, hemorrhaged for 45 min, and randomly assigned to receive an infusion of hypertonic saline (7.5%, 2,400 mOsm total; 6 mL/kg; n = 6) or hypertonic saline with 50, 100, or 300 mg/kg L-arginine (2,400 mOsm; 6 mL/kg; n = 6 in each of the three dose groups) and then monitored for 120 min after the end of infusion. CBF was measured continuously and calculated as a percent of the pre-TBI baseline during the hemorrhage period, after reinfusion of one of the hypertonic arginine solutions, and 30, 60, and 120 min after reinfusion. All four hypertonic solutions initially improved MAP, which, by 120 min after infusion, had decreased nearly to the levels observed during hemorrhage. ICP remained below baseline levels during resuscitation in all groups, although ICP was slightly greater (P = NS) than baseline in the hypertonic saline group. CBF increased similarly in all groups during infusion and then decreased similarly in all groups. At 120 min after infusion, CBF was highest in the group infused with hypertonic saline, but the difference was not significant. We conclude that the improvement of MAP, ICP, and CBF produced by hypertonic saline alone after TBI and hemorrhagic hypotension is not significantly enhanced by the addition of L-arginine at these doses.

Animals↗
PubMed2006

Isoflurane inhibits compensatory intravascular volume expansion after hemorrhage in sheep.

After hemorrhage, blood volume is partially restored by transcapillary refill, a process of spontaneous compensatory intravascular volume expansion that we hypothesized would be inhibited by anesthesia. Six chronically instrumented sheep were subjected to four randomly ordered experiments while conscious or during anesthesia with isoflurane. After plasma volume measurement (indocyanine green), 15% or 45% of the blood volume was withdrawn. To quantify transcapillary refill, mass balance and kinetic calculations utilized repeated measurements of hemoglobin concentration, assuming that transcapillary refill would dilute hemoglobin concentration. After 15% hemorrhage, mean arterial blood pressure remained stable in both conscious and isoflurane-anesthetized sheep (normotensive hemorrhage) but decreased after 45% hemorrhage (hypotensive hemorrhage). After either normotensive or hypotensive hemorrhage, transcapillary refill occurred more rapidly during the first 40 min than during the next 140 min (P < 0.001). In conscious sheep, at 180 min, 57% and 42% of the bled volume had been restored after normotensive and hypotensive hemorrhage, respectively, in contrast to only 13% and 27% (P < 0.001) in isoflurane-anesthetized sheep. A novel kinetic model implicated hemodynamic factors in rapid, early transcapillary refill and decreased plasma oncotic pressure in subsequent slower filling. We conclude that isoflurane inhibits transcapillary refill after both normotensive and hypotensive hemorrhage in sheep.

Anesthetics, Inhalation↗
PubMed2005

Optoacoustic monitoring of blood hemoglobin concentration: a pilot clinical study.

The optoacoustic technique is noninvasive, has high spatial resolution, and potentially can be used to measure the total hemoglobin concentration ([THb]) continuously and accurately. We performed in vitro measurements in blood and in vivo tests in healthy volunteers. Our clinical protocol included rapid infusion of intravenous saline to simulate rapid change in the [THb] during fluid therapy or surgery. Optoacoustic measurements were made from the wrist area overlying the radial artery for more than 1 h. The amplitude of the optoacoustic signal generated in the radial artery closely followed the [THb] measured directly in concurrently collected blood samples.

Acoustics↗
PubMed2005

Dose-dependent neuronal injury after traumatic brain injury.

The Fluoro-Jade (FJ) stain reliably identifies degenerating neurons after multiple mechanisms of brain injury. We modified the FJ staining protocol to quickly stain frozen hippocampal rat brain sections and to permit systematic counts of stained, injured neurons at 4 and 24 h after mild, moderate or severe fluid percussion traumatic brain injury (TBI). In adjacent sections, laser capture microdissection was used to collect uninjured (FJ negative) CA3 hippocampal neurons to assess the effect of injury severity on mRNA levels of selected genes. Rats were anesthetized, intubated, mechanically ventilated and randomized to sham, mild (1.2 atm), moderate (2.0 atm) or severe (2.3 atm) TBI. Four or 24 h post-TBI, ten frozen sections (10 microm thick, every 15th section) were collected from the hippocampus of each rat, stained with FJ and counterstained with cresyl violet. Fluoro-Jade-positive neurons were counted in hippocampal subfields CA1, CA3 and the dentate gyrus/dentate hilus. At both 4 and 24 h post-TBI, numbers of FJ-positive neurons in all hippocampal regions increased dose-dependently in mildly and moderately injured rats but were not significantly more numerous after severe injury. Although analysis of variance demonstrated no overall difference in expression of mRNA levels for heat shock protein 70, bcl-2, caspase 3, caspase 9 and interleukin-1beta in uninjured CA3 neurons at all injury levels, post hoc analysis suggested that TBI induces increases in neuroprotective gene expression that offset concomitant increases in deleterious gene expression.

Analysis of Variance↗
PubMed2005

Peroxynitrite generated at the level produced by spinal cord injury induces peroxidation of membrane phospholipids in normal rat cord: reduction by a metalloporphyrin.

The goal of the present study was to determine in vivo whether peroxynitrite, at the concentration and duration produced by SCI, contributes to membrane lipid peroxidation (MLP) after traumatic spinal cord injury (SCI) and the capability of a broad spectrum scavenger of reactive species, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to reduce MLP. This was accomplished by administering a peroxynitrite donor 3-morpholinosydnonimine (SIN-1) into the gray matter of an uninjured rat spinal cord through a microdialysis fiber to generate ONOO at the SCI-elevated levels. The resulting MLP was characterized by measuring the productions of extracellular malondialdehyde and of intracellular 4-hydroxynonenal. We demonstrated that extracellular SIN- 1 administration significantly increased the concentration of malondialdehyde (p < 0.001) and the numbers of hydroxynonenal-positive cells (p < 0.001) as compared to a control group in which ACSF was administered. Simultaneous administration of MnTBAP through a second microdialysis fiber significantly reduced SIN-1-induced malondialdehyde production (p < 0.001) and the numbers of HNE-positive cells (p < 0.001). There was no significant difference between MnTBAP-treated and ACSF-controls (p = 0.3). These results demonstrate in vivo that (1) SCI-produced levels of peroxynitrite sufficient to cause MLP, and therefore that peroxynitrite is an agent of secondary damage after acute SCI; (2) MnTBAP can efficiently reduce SIN-1-induced MLP.

Aldehydes↗
PubMed2005

Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep.

BACKGROUND: Current, invasive cerebral oxygenation monitors require either retrograde jugular venous bulb cannulation or intraparenchymal probe insertion. There is no accurate, noninvasive, continuous monitor of cerebral blood oxygenation. METHODS: The authors designed, built, and tested novel optoacoustic instrumentation that continuously measures blood oxygenation in the superior sagittal sinus (SSS) in vivo in 12 anesthetized sheep. In this technique, laser pulses generate acoustic signals, the amplitudes and slopes of which are proportional to oxyhemoglobin saturation in the SSS. Optoacoustic signals from the SSS measured through the scalp and cranium were compared with directly measured oxyhemoglobin saturation in blood withdrawn from the cannulated SSS. RESULTS: In the first experiments (feasibility), FIO2 changes produced rapid corresponding changes in optoacoustic signals and arterial oxygen saturation. In the second experiments (validation), the authors correlated oxyhemoglobin saturation in the SSS with optoacoustic signals and developed quantifying algorithms. In eight of nine validation experiments, the authors quantified optoacoustic signals by subtracting the temporal profile at low FIO2 (0.08-0.1) from profiles at higher FIO2 and integrating those signals in the range from 3 to 5 micros. In each validation experiment, optoacoustic signals showed tight temporal association and good linear correlation with measured oxyhemoglobin saturation (r2 0.75 to 0.99 for eight individual experiments). CONCLUSIONS: The optoacoustic system detects signals induced in the SSS and optoacoustic signals from the SSS linearly correlate with oxyhemoglobin saturation. The data suggest that the optoacoustic technique merits clinical evaluation.

Acoustic Stimulation↗
PubMed2005

Traumatic brain injury and hemorrhagic hypotension suppress neuroprotective gene expression in injured hippocampal neurons.

BACKGROUND: After traumatic brain injury, memory dysfunction is due in part to damage to the hippocampus. To study the molecular mechanisms of this selective vulnerability, the authors used laser capture microdissection of neurons stained with Fluoro-Jade to directly compare gene expression in injured (Fluoro-Jade-positive) and adjacent uninjured (Fluoro-Jade-negative) rat hippocampal neurons after traumatic brain injury and traumatic brain injury plus hemorrhagic hypotension. METHODS: Twelve isoflurane-anesthetized Sprague-Dawley rats underwent moderate (2.0 atm) fluid percussion traumatic brain injury followed by either normotension or hemorrhagic hypotension. Animals were killed 24 h after injury. Frozen brain sections were double stained with 1% cresyl violet and 0.001% Fluoro-Jade. RNA from 10 Fluoro-Jade-positive neurons and 10 Fluoro-Jade-negative neurons, obtained from the hippocampal CA1, CA3, and dentate gyrus subfields using laser capture microdissection, was linearly amplified and analyzed by quantitative ribonuclease protection assay for nine neuroprotective and apoptosis-related genes. RESULTS: In injured CA3 neurons, expression of the neuroprotective genes glutathione peroxidase 1, heme oxygenase 1, and brain-derived neurotrophic factor was significantly decreased compared with that of adjacent uninjured neurons. Superimposition of hemorrhagic hypotension was associated with down-regulation of neuroprotective genes in both injured and uninjured neurons of all subregions. Expression of apoptosis-related genes did not vary between injured and uninjured neurons, with or without superimposed hemorrhage. CONCLUSIONS: The authors show, in the first direct comparison of messenger RNA levels in injured and uninjured hippocampal neurons, that injured neurons express lower levels of neuroprotective genes than adjacent uninjured neurons.

Animals↗
PubMed2005

Volume turnover kinetics of fluid shifts after hemorrhage, fluid infusion, and the combination of hemorrhage and fluid infusion in sheep.

BACKGROUND: Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts. METHODS: Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion. RESULTS: The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments. CONCLUSION: Volume turnover kinetics is a promising tool for explaining fluid shifts between body compartments after perturbations such as hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal output after hemorrhage prevailed regardless of fluid infusion and caused fluid retention, which expanded the tissue compartment.

Algorithms↗