Diagnostics development for quasi-steady-state operation of the Wendelstein 7-X stellarator (invited).

The critical issues in the development of diagnostics, which need to work robust and reliable under quasi-steady state conditions for the discharge durations of 30 min and which cannot be maintained throughout the one week duration of each operation phase of the Wendelstein 7-X stellarator, are being discussed.

Diagnostics design for steady-state operation of the Wendelstein 7-X stellarator.

The status of the diagnostic developments for the quasistationary operable stellarator Wendelstein 7-X (maximum pulse length of 30 min at 10 MW ECRH heating at 140 GHz) will be reported on. Significant emphasis is being given to the issue of ECRH stray radiation shielding of in-vessel diagnostic components, which will be critical at high density operation requiring O2 and OXB heating.

The effect of poly-L-lysine/alginate bead membrane characteristics on the absorption of heparin.

During extracorporeal procedures like hemodialysis, heparin is administered to patients to prevent clotting. Unfractionated heparin has side effects such as excessive bleeding. It would be advantageous if the blood could be deheparinased before it returns to the patient. Previous work has indicated that poly-L-lysine/alginate beads can efficiently remove heparin from saline solutions 1. Heparin is irreversibly absorbed onto the beads. This article explores ways of optimizing the absorption process by performing in vitro rate experiments with varying physical parameters of the beads. Fetal calf serum and blood are also used in experiments to investigate the possibility of designing a safe and efficient reactor to absorb heparin. All the experiments were performed to obtain the required parameters for optimal reactor design. The results indicate that the absorption could be optimized by controlling the membrane thickness of the beads. The beads also showed efficient removal of heparin from whole blood.

Diagnostic developments for quasicontinuous operation of the Wendelstein 7-X stellarator.

The stellarator Wendelstein 7-X will allow for quasicontinuous operation with the duration only being limited to two 30 min discharges per day, at a continuous heating power of 10 MW electron cyclotron resonance heating (ECRH) at 140 GHz, by the capacity of the cooling water reservoir. This will result in high thermal loads on all plasma facing components of 50-100 kW/m(2) from radiation alone and of up to about 500 kW/m(2) on components additionally exposed to convective loads. In high density scenarios toroidally varying ECRH stray radiation levels of 50-200 kW/m(2) need to be coped with, requiring careful material selection and different shielding and hardening techniques. Furthermore, a gradual buildup of coatings on plasma facing optical components, which without any measures being taken, would lead to high transmission losses already within a few days of long pulse operation (equivalent to about 1 year of operation in pulsed devices like JET or ASDEX-upgrade) and therefore needs to be prevented as much as possible. In addition in situ cleaning as well as absolute calibration techniques need to be developed for all plasma facing optical systems. Here we report about some of our efforts to find, for various types of diagnostics, ways to cope with these adverse effects. Moreover, we give a few examples for individual diagnostic specific issues with respect to quasicontinuous operation, such as the development of a special integrator for the magnetic diagnostics as well as special interferometer types which can cope with unavoidable vibrations and slow path length changes due to, e.g., thermal expansion of the plasma vessel.

Optical design study of an infrared visible viewing system for Wendelstein 7-X divertor observation and control.

For the Wendelstein 7-X stellarator, which will allow quasicontinuous operation (tau < or = 30 min) with 10 MW of electron cyclotron radiation heating power, a conceptual design study for an IR/visible viewing system (IVVS) has been elaborated. Ten such systems, as part of the machine protection system, will be required for real time monitoring of all ten discrete, water cooled divertor modules with high spatial (< 10 mm) resolution, in order to prevent local overheating of the target tiles, which could easily lead to their destruction. On the physics side, the systems will be used for divertor symmetry investigations by studying the power load distribution on all targets modules and by observing the island divertor plasmas in the light of H alpha, C II, and C III using the visible imaging section of the systems. The optics of the system can be divided into three parts: a mirror based optical head, creating an intermediate image, a Cassegrain telescope system, and individual lens based imaging optics adapted to the various detectors for IR (3-5 microm and 8-14 microm) and visible observations, with their optical light paths being separated by in-vacuum dichroic beam splitters.

Efficiency of polymer beads in the removal of heparin: toward the development of a novel reactor.

Administration of heparin during extracorporeal procedures increases the risk of haemorrhage. Various reactor designs, including the use of heparinase and poly-L-lysine. HBr hollow fiber, have been investigated for the removal of heparin prior to the blood being returned to the patient; however, none of them have been implemented clinically. In this paper it is proposed that beads made from poly-L-lysine/alginate can be used to remove the heparin. The aim of this work is to perform the necessary experiments in order to get the information required to design a heparin removal reactor that uses these beads. The experiments are aimed at measuring the removal rates of heparin by the beads, testing the efficiency of the beads to remove heparin, determining repeatability and identifying factors that could influence the removal rate. Batch rate experiments using poly-L-lysine/alginate beads in saline solutions were performed to investigate the removal rate of heparin. The results, which indicate that heparin is efficiently removed, may lead to improved bioreactor designs.

New advanced operational regime on the W7-AS stellarator.

A promising new plasma operational regime on the Wendelstein stellarator W7-AS has been discovered. It is extant above a threshold density and characterized by flat density profiles, high energy and low impurity confinement times, and edge-localized radiation. Impurity accumulation is avoided. Quasistationary discharges with line-averaged densities n(e) to 4 x 10(20) m(-3), radiation levels to 90%, and partial plasma detachment at the divertor target plates can be simultaneously realized. Energy confinement is up to twice that of a standard scaling. At B(t) = 0.9 T, an average beta value of 3.1% is achieved. The high n(e) values allow demonstration of electron Bernstein wave heating using linear mode conversion.

Sustained influence of the renal nerves to attenuate sodium retention in angiotensin hypertension.

Recent studies indicate that baroreflex suppression of renal sympathetic nerve activity is sustained for up to 5 days of ANG II infusion; however, steady-state conditions are not associated with ANG II hypertension of this short duration. Thus the major goal of this study was to determine whether neurally induced increments in renal excretory function during chronic intravenous infusion of ANG II are sustained under more chronic conditions when hypertension is stable and sodium balance is achieved. Experiments were conducted in five conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. ANG II was infused after control measurements for 10 days at a rate of 5 ng. kg(-1). min(-1). Twenty-four-hour control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 92 +/- 4 mmHg and 0.99 +/- 0.05, respectively. On days 8-10 of ANG II infusion, MAP was stable (+30 +/- 3 mmHg) and sodium balance was achieved. Whereas equal amounts of sodium were excreted from the kidneys during the control period, throughout ANG II infusion there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 10 Den/Inn sodium = 0.56 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. The greater rate of sodium excretion in Inn vs. Den kidneys during renal sympathoinhibition also revealed a latent impairment in sodium excretion from Den kidneys. Although the Den/Inn for sodium and the major metabolites of nitric oxide (NO) decreased in parallel during ANG II hypertension, the Den/Inn for cGMP, a second messenger of NO, remained at control levels throughout this study. This disparity fails to support the notion that a deficiency in NO production and action in Den kidneys accounts for the impaired sodium excretion. Most importantly, these results support the contention that baroreflex suppression of renal sympathetic nerve activity is sustained during chronic ANG II hypertension, a response that may play an important role in attenuating the rise in arterial pressure.

Obesity hypertension: role of leptin and sympathetic nervous system.

Obesity may account for as much as 65% to 75% of human essential hypertension in most industrialized countries. Excess renal sodium reabsorption and a hypertensive shift of renal-pressure natriuresis play a key role in mediating obesity hypertension. Sympathetic activation contributes to obesity-induced sodium retention and hypertension because adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with other neurochemical pathways in the hypothalamus may be a partial link between excess weight gain and increased sympathetic activity. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term intravenous leptin infusions in nonobese rodents at rates that raise plasma concentrations to the levels found in severe obesity increase arterial pressure and heart rate through adrenergic activation. Also, transgenic mice that overexpress leptin develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including melanocortin-4 receptors. However, it is unclear whether this pathway or others, such as neuropeptide Y, mediate the long-term effects of leptin on blood pressure. In addition, leptin has other actions, such as stimulation of nitric oxide formation and enhancement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the precise role of these complex interactions in human obesity has not been elucidated, this is an important area for further investigation, especially considering the current epidemic of obesity in most industrialized countries.

Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension.

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(-1). min(-1). In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.

Role of sympathetic nervous system and neuropeptides in obesity hypertension.

Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R). However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this remains a fruitful area for further investigation, especially in view of the current "epidemic" of obesity in most industrialized countries.

Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay.

The role of the opioid-like receptor 1 (ORL1) and its endogenous ligand, nociceptin/orphanin FQ (N/OFQ), in nociception, anxiety, and learning remains to be defined. To allow the rapid identification of agonists and antagonists, a reporter gene assay has been established in which the ORL1 receptor is functionally linked to the cyclic AMP-dependent expression of luciferase. N/OFQ and N/OFQ(1-13)NH(2) inhibited the forskolin-induced luciferase gene expression with IC(50) values of 0.81 +/- 0.5 and 0.87 +/- 0.16 nM, respectively. Buprenorphine was identified as a full agonist at the ORL1 receptor with an IC(50) value of 8.4 +/- 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ((1-13))NH(2) clearly behaved as an agonist in this assay with an IC(50) value of 85 +/- 47 nM. Thus, there is still a need for antagonistic tool compounds that might help to elucidate the neurophysiological role of N/OFQ.

Cardiovascular regulation during insulin infusion into the carotid or vertebral artery in dogs.

OBJECTIVE: To test the hypothesis that insulin increases heart rate and arterial pressure via direct effects on the central nervous system. METHODS AND DESIGN: Insulin was infused into the cerebral circulation of conscious dogs (n = 8) chronically instrumented for continuous infusions and measurement of arterial pressure, cardiac output, heart rate and other hemodynamic variables. In acute experiments, insulin was infused for 30 min into either a carotid or vertebral artery at several rates calculated to increase cerebral circulation insulin concentrations to levels in the physiological or pathophysiological range. It was infused with and without a simultaneous glucose infusion. During long-term experiments, insulin was infused into either a carotid or a vertebral artery for 4 days at 0.4 or 0.2 mU/kg per min, respectively. RESULTS: Insulin infusion alone into the cerebral circulation produced no changes in any measured cardiovascular variable. A simultaneous glucose infusion also produced no changes in cardiovascular dynamics, except at the highest rate of infusion into the carotid artery. The changes seen at the highest rate of infusion are unlikely to be insulin-induced, since similar changes occurred when either glucose or saline was infused in the absence of any insulin infusion. Long-term insulin infusion (4 days) into carotid or vertebral arteries also produced no changes in any measured cardiovascular or renal variable. CONCLUSIONS: These results provide no evidence that insulin, at physiological or pathophysiological concentrations, increases heart rate or arterial pressure by acting directly on the central nervous system, and suggest that sympathetic activation and tachycardia previously observed with systemic hyperinsulinemia may be secondary to peripheral actions of insulin.

Renal nerves promote sodium excretion during long-term increases in salt intake.

To determine whether the renal nerves contribute to sodium homeostasis during long-term increments in sodium intake, studies were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-hour urine collection from denervated and innervated kidneys. They were fed a low sodium diet and continuously infused with isotonic saline (350 mL/d) to provide a daily sodium intake of approximately 60 mmol. After control measurements, sodium intake was increased to 470 mmol/d by increasing the rate of isotonic saline infusion to 3000 mL/d for 5 days; this was followed by a 5-day recovery period. Twenty-four-hour control values for mean arterial pressure and ratios for urinary sodium, potassium, and creatinine excretion from denervated and innervated kidneys (DEN/INN) were 96+/-3, 1.06+/-0.04, 1.00+/-0.04, and 1.01+/-0.02 mm Hg, respectively. During the approximately 8-fold increase in sodium intake, there was no long-term change in mean arterial pressure, and daily sodium balance was achieved within 48 hours. Moreover, during the first day of high salt intake, there were significant reductions in the DEN/INN for sodium and potassium excretion, which persisted for the entire 5-day period of increased sodium intake; on day 5, the DEN/INN for sodium and potassium excretion was 0.86+/-0.03 and 0.86+/-0.04, respectively. In contrast, the DEN/INN for creatinine excretion remained at control levels during high salt intake. Furthermore, similar long-term reductions in the DEN/INN for sodium and potassium excretion occurred in a second group of dogs administered adrenergic receptor-blocking agents for 5 days to interrupt the functional effects of the renal nerves. These data indicate that sustained renal sympathoinhibition promotes sodium and potassium excretion during long-term increments in sodium intake by inhibiting tubular reabsorption of these electrolytes.

Renal nerves promote sodium excretion in angiotensin-induced hypertension.

To determine whether the sympathetic nervous system contributes to the hypertension induced by pathophysiological increments in plasma angiotensin II (Ang II) concentration, we determined the neurally induced changes in renal excretory function during chronic intravenous infusion of Ang II. Studies were carried out in five conscious chronically instrumented dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-hour urine collection from the denervated and innervated kidneys. After control measurements, Ang II was infused for 5 days at a rate of 4.8 pmol/kg per minute (5 ng/kg per minute); this was followed by a 5-day recovery period. Twenty-four-hour control values for mean arterial pressure (MAP) and for the ratio of denervated to innervated kidneys (DEN/INN) for urinary sodium, potassium, and creatinine excretion were 93+/-5 mm Hg, 1.17+/-0.09, 1.10+/-0.10, and 1.00+/-0.02, respectively. As expected, Ang II infusion caused sodium retention for several days before sodium balance was achieved at an elevated MAP (day 5=124+/-4 mm Hg). Moreover, by day 2 of Ang II-induced hypertension, there were significant reductions in the DEN/INN for sodium and potassium, which persisted for the 5 days of Ang II infusion; on day 5, the DEN/INN values for sodium and potassium were 0.71+/-0.10 and 0.91+/-0.12, respectively. In contrast, the DEN/INN for creatinine was unchanged from control levels during Ang II infusion, and measurements of renal hemodynamics indicated comparable reductions in glomerular filtration rate (approximately 13%) and renal plasma flow (approximately 25%) during Ang II infusion. This indicates that the renal nerves promoted sodium and potassium excretion during Ang II-induced hypertension by inhibiting tubular reabsorption of these electrolytes. Thus, this study provides no support for the hypothesis that increased renal sympathetic nerve activity impairs sodium excretion and contributes to Ang II-induced hypertension.

EIectrical impedance and transepidermal water loss of healthy human skin under different conditions.

BACKGROUND/AIMS: The skin barrier function is a multidimensional quality, which can be defined by a combination of noninvasive measurements, including EIectrical impedance (EI) and transepidermal water loss (TEWL). METHODS: TEWL and EI were determined on in five different areas of the body in 25 healthy volunteers. The effects of hydration (a 15 min water bath, a 1 h occlusion and application of an oil-in-water emulsion combined with occlusion) were measured on the volar forearm. RESULTS: EI was highest in the axillary region, followed by the cheek, spinal region, presternal area and upper arm. TEWL was highest in the axillary region, followed by the cheek. Lowest levels were detected in the spinal region, the presternal region and the upper arm. The water bath increased EI but not TEWL. After 1 h occlusion TEWL was not increased and EI decreased, which corresponds to stratum corneum hydration. After a single application of an oil-in-water emulsion, we observed a reduction of EI and an increase of TEWL. The simultaneous use of occlusion and application of an emulsion led to the most significant reduction of EI. TEWL was increased during the following 30 min. CONCLUSIONS: EI and TEWL show a topological variability. Acute hydration increased EI but occlusion and/or moisturizing decreased EI. Acute hydration and occlusion alone did not significantly affect TEWL, but moisturizing in combination caused a longer lasting TEWL increase. To examine the stratum corneum function, the use of different noninvasive techniques seem to provide more complex information.

Long-term dietary supplementation with L-arginine prevents age-related reduction in renal function.

Aging is associated with loss of nephron function and reductions in serum L-arginine and excretion of nitric oxide (NO) metabolites. The present study was performed to determine if long-term dietary treatment with L-arginine, the NO synthase substrate, could prevent age-related renal injury. Studies were performed in four groups of rats, aged 12-13 mo, for 8 mo: group 1 received L-arginine (2% in 2.5% corn syrup, n = 5); group 2 received sodium nitrite, an NO donor (0.1%, in 2.5% syrup, n = 7); group 3 was an untreated control group (n = 7); group 4 was treated with 2.5% corn syrup (n = 5). Urinary protein increased and urinary nitrate/nitrite decreased with age in controls, but, during L-arginine treatment, urinary protein decreased and nitrate/nitrite increased. Two weeks after L-arginine was stopped, urinary protein had increased and nitrate/nitrite had decreased to the same level as in controls. L-Arginine treatment increased glomerular filtration rate (GFR) by 50% compared with untreated controls. In contrast, nitrite had no effect on GFR. Morphologically, L-arginine protected against aging injury by reducing the number of sclerotic glomeruli. In summary, we found that L-arginine prevented the age-related glomerular injury and reduction in GFR. The mechanism of protection, however, may be independent of NO.

Laboratory and field evaluation of deet, CIC-4, and AI3-37220 against Anopheles dirus (Diptera: Culicidae) in Thailand.

Laboratory and field tests of the repellents diethyl methylbenzamide (deet), 1-(3-Cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), and (2-hydroxymethylcyclohexyl) acetic acid lactone (CIC-4) were conducted against Anopheles dirus Peyton & Harrison, the principal malaria vector in Thailand. In the laboratory, An. dirus was more sensitive to CIC-4 than either AI3-37220 or deet. The duration of protection provided by each repellent in laboratory tests increased with higher concentrations of repellents and when exposed in cages containing fewer mosquitoes. A field study in Chanthaburi Province, southeastern Thailand, during November 1993 tested 25% (wt:wt) ethanol solutions of each repellent against An. dirus. In contrast to the laboratory experiments, protection provided by AI3-37220 was significantly better than either deet or CIC-4 and there was no significant difference between deet and CIC-4. Protection provided by deet and CIC-4 fell to below 95% 2 h after repellent application, whereas AI3-37220 provided > 95% protection for 4 h. The protection provided by all repellents fell to < or = 65% 7 h after repellent application.

Influence of the renal nerves on sodium excretion during progressive reductions in cardiac output.

The purpose of this study was to elucidate the role of the renal nerves in promoting sodium retention during chronic reductions in cardiac output. In five dogs, the left kidney was denervated and the urinary bladder was surgically divided to allow separate 24-h urine collection from the innervated and denervated kidneys. Additionally, progressive reductions in cardiac output were achieved by employing an externally adjustable occluder around the pulmonary artery and by servo-controlling right atrial pressure (control = 0.9 +/- 0.2 mmHg) at 4.7 +/- 0.1, 7.5 +/- 0.1, and 9.8 +/- 0.2 mmHg for 3 days at each level. At the highest level of right atrial pressure, the 24-h values for mean arterial pressure (control = 97 +/- 3 mmHg) and cardiac output (control = 2,434 +/- 177 ml/min) were reduced approximately 25 and 55%, respectively; glomerular filtration rate fell by approximately 35% and renal plasma flow by approximately 65%. However, despite the sodium retention induced by these hemodynamic changes, there were no significant differences in renal hemodynamics or sodium excretion between the two kidneys during pulmonary artery constriction. In contrast, after release of the pulmonary artery occluder on day 9, sodium excretion increased more (approximately 28% during the initial 24 h) in innervated than in denervated kidneys. These results suggest that the renal nerves are relatively unimportant in promoting sodium retention in this model of low cardiac output but contribute significantly to the short-term elimination of sodium after partial restoration of cardiac output and mean arterial pressure.

An anatomic and physiological model of hepatic vascular system.

Hepatic function can be characterized by the activity/time curves obtained by imaging the aorta, spleen, and liver. Nonparametric deconvolution of the activity/time curves is clinically useful as a diagnostic tool in determining organ transit times and flow fractions. The use of this technique is limited, however, because of numerical and noise problems in performing deconvolution. Furthermore, the interaction of part of the tracer with the spleen and gastrointestinal tract, before it enters the liver, further obscures physiological information in the deconvolved liver curve. In this paper, a mathematical relationship is derived relating the liver activity/time curve to portal and hepatic behavior. The mathematical relationship is derived by using transit time spectrum/residence time density theory. Based on this theory, it is shown that the deconvolution of liver activity/time curves gives rise to a complex combination of splenic, gastrointestinal, and liver dependencies. An anatomically and physiologically plausible parametric model of the hepatic vascular system has been developed. This model is used in conjunction with experimental data to estimate portal, splenic, and hepatic physiological blood flow parameters for eight normal volunteers. These calculated parameters, which include the portal flow fraction, the splenic blood flow fraction, and blood transit times are shown to adequately correspond to published values. In particular, the model of the hepatic vascular system identifies the portal flow fraction as 0.752 +/- 0.022, the splenic blood flow fraction as 0.180 +/- 0.023, and the liver mean transit time as 13.4 +/- 1.71 s. The model has also been applied to two portal hypertensive patients. The variation in some of the model parameters is beyond normal limits and is consistent with the observed pathology.