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To investigate the relationship between red blood cell distribution width (RDW) and residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seventy-seven CAPD patients were enrolled in this study. According to receiver operator characteristic (ROC) curve analysis, patients were divided into high RDW (RDW > 14.95%) and low RDW (RDW ≤ 14.95%) groups. The data of baseline clinical, biochemical parameters, comorbidities, medication status, peritoneal function, and dialysis adequacy were compared. Survival curves were calculated using Kaplan-Meier method. Cox regression model was employed to analyze risk factors of decline in RRF. The overall median survival time was 24 months, the median survival time of high RDW group (46 patients) and low RDW group (31 patients) were 24 and 12 months, respectively. Compared with the low RDW group, patients in the high RDW group were older, higher rate of decline RRF and white blood cells count as well as lower total Kt/V (all p

Background: A majority of hospice care is delivered at home, with significant caregiver involvement. Identifying factors associated with caregiver-reported quality measures could help improve hospice care in the United States. Objectives: To identify correlates of caregiver-reported quality measures: burden, satisfaction, and quality of end-of-life (EoL) care in home hospice care. Design: A cross-sectional study was conducted from April 2017 through February 2018. Setting/Subjects: A nonprofit, urban hospice organization. We recruited caregivers whose patients were discharged from home hospice care. Eligible caregiver participants had to be 18 years or older, English-speaking, and listed as a primary caregiver at the time the patient was admitted to hospice. Measures: The (1) short version of the Burden Scale for Family Caregivers; (2) Family Satisfaction with Care; and (3) Caregiver Evaluation of the Quality of End-Of-Life Care. Results: Caregivers (n = 391) had a mean age of 59 years and most were female (n = 297, 76.0%), children of the patient (n = 233, 59.7%), and non-Hispanic White (n = 180, 46.0%). The mean age of home hospice patients was 83 years; a majority had a non-cancer diagnosis (n = 235, 60.1%), were female (n = 250, 63.9%), and were non-Hispanic White (n = 210, 53.7%). Higher symptom scores were significantly associated with greater caregiver burden and lower satisfaction with care; but not lower quality of EoL care. Caregivers who were less comfortable managing patient symptoms during the last week on hospice had higher caregiver burden, lower caregiver satisfaction, and lower ratings of quality of EoL care. Conclusion: Potentially modifiable symptom-related variables were correlated with caregiver-reported quality measures. Our study reinforces the important relationship between the perceived suffering/symptoms of patients and caregivers' hospice experiences.

Background: Symptoms (e.g., pain, shortness of breath, and fatigue) at the end of life (EoL) are common. Although symptoms can contribute to poor quality of life at the EoL, much remains unknown regarding their prevalence and correlates in home hospice care. Objectives: To determine the prevalence and correlates of caregiver-reported symptoms in home hospice patients during the last week before discharge using the Edmonton Symptom Assessment Scale (ESAS). Design: This is a cross-sectional study measuring perceived patient symptoms using caregiver proxy data. Bivariate and multivariate analyses were conducted to examine patient and caregiver characteristics associated with ESAS scores. Setting/Subjects: Subjects were from an urban nonprofit home hospice organization. Measurements: Symptoms were measured using the ESAS. Results: The mean ESAS score was 51.2 (SD ±17.4). In bivariate analyses, higher perceived symptom score was associated with younger patient age (p

Molecular switches enable the fabrication of multifunctional devices in which an electrical output can be modulated by external stimuli. The working mechanism of these devices is often hard to prove, since the molecular switching events are only indirectly confirmed through electrical characterization, without real-space visualization. Here, we show how photochromic molecules self-assembled on graphene and MoS2 generate atomically precise superlattices in which a light-induced structural reorganization enables precise control over local charge carrier density in high-performance devices. By combining different experimental and theoretical approaches, we achieve exquisite control over events taking place from the molecular level to the device scale. Unique device functionalities are demonstrated, including the use of spatially confined light irradiation to define reversible lateral heterojunctions between areas possessing different doping levels. Molecular assembly and light-induced doping are analogous for graphene and MoS2, demonstrating the generality of our approach to optically manipulate the electrical output of multi-responsive hybrid devices., Photochromic molecules offer the unique opportunity to demonstrate multifunctional devices with light-tunable electrical characteristics. Gobbi et al. build light-switchable electronic heterojunctions based on atomically precise, photo-reversible molecular superlattices on graphene and MoS2.

—This paper presents the designs of kiloampere-classreactors with high temperature superconducting (HTS) BSCCOtapes. The HTS solenoidal windings of the 100 A-class andkiloampere-class reactors consist of 34 coil layers and 136 coilturns in total. The structural design and performance evaluations,including critical current and ac loss calculations are discussedfor a single-phase grounding fault case and compared with a con-ventional copper reactor. The method to apply the HTS tapes andthe principal features of the HTS reactors have been theoreticallyidentified. Index Terms — AC loss, BSCCO, current limiting reactor, neu-tral grounding reactor, superconducting reactor. I. I NTRODUCTION R EACTORS ARE widely used in modern power systems,which provide functions such as limiting currents, com-pensation of power, and inductive connection to ground. Powerquality and reliability problems are normally caused by theabnormal operations of large-scale equipments and the short-circuit faults caused by the power system itself. High tempera-ture superconductors (HTSs) have been successfully applied inthe advanced reactor developments. As an example, a numberofreactor-basedsuperconductingfaultcurrentlimiters(SFCLs)including the saturated iron-core type [1], [2], transformer type[3], [4] reactor type [5], [6], and non-inductive type [7] aremadeavailabletoreducethefaultcurrentlevelsontransmissionand distribution networks.The power system faults mainly include three-phase shortcircuit, two-phase short circuit, two-phase grounding short cir-cuit and single-phase grounding short circuit. The single-phasegrounding faults, for example, account for about 91.23% of thetotal number of power system faults in the 6434 power trans-mission lines of 220 kV Chinese power grid in 2008. It meansthat single-phase grounding faults need to be solved urgently toimprove the whole power system quality and reliability [8].In the neutral indirectly grounded power systems, the single-phase grounding fault occurs most frequently. The three-phaseline voltages still keep symmetrical states and have negligibleimpact to the local power equipments. Therefore, the powersystem is allowed to continue running up to few hours before

A novel dish Stirling solar power generation (DSSPG) system has been designed incorporated with a high temperature superconducting (HTS) linear synchronous generator (LSG). The high efficient HTSLSG is a compact energy converter for a Stirling engine in the DSSPG system, where a duplex of Stirling cycles is applied, in which a Stirling engine replaces the conventional linear compressor forming a Stirling pulse tube refrigerator (SPTR). This paper presents the DSSPG system designed with the HTSLSG cooled by the duplex Stirling system, and analyzes the thermal load and power distribution in the system to provide bases for consideration of practical application. Analysis results show that the DSSPG system with the HTSLSG refrigerated by the SPTR powered by the DSSPG system itself can be realized, and has higher efficiency than that with the conventional LSG and has larger system capacity.

Superconducting magnetic energy storage (SMES) technology has been progressed actively for use in modern power system. Principal application schemes of a sole SMES system, a hybrid energy storage system (HESS) consisting of small-scale SMES and other commercial energy storage systems (ESSs), a distributed SMES (DSMES) system, and a distributed HESS (DHESS) are presented and compared. The concept of the SMES-based HESS provides an economical way to apply medium-scale SMES systems in daily load leveling and to apply small-scale SMES systems in power quality improvement. A dc power distribution network case with superconducting dc cables and SMES devices is conceptually designed to evaluate the performance of the proposed four SMES application schemes. The results show that the novel concept of the SMES-based DHESS can be particularly expected to achieve efficient and economical power management. Finally, the application prospects and possible schemes implanting SMES devices for power generation, transmission, distribution and utilization are explored for use in future smart grid.

This paper presents a computer-controlled test platform for superconducting magnetic energy storage (SMES) control and measurement based on the Laboratory Virtual Instrument Engineering Workbench (LabVIEW). The purpose is to achieve the fast control and friendly measurement simultaneously by integrating the LabVIEW and commercial digital control chips. The test platform mainly consists of three modules, i.e., power conditioning system (PCS) module, control module and measurement module. The PCS module imitates the operational conditions and characteristics of a practical SEMS device by using the combination of a programmable power source and an equivalent load network. A LabVIEW-based program is also designed to output various imitated charge-discharge current waveforms to directly supply the SMES magnet so as to avoid the use of the complicated and costly practical PCS. The measurement module has multi-functions of current-voltage (I-V), temperature and magnetic field measurements. In cooperation with the control module, the measured data are applied to adjust the real-time operational state of the PCS module and to protect the SMES magnet when the quench is detected. The test platform has been experimentally verified for the use in a small-scale SMES prototype.

To date the diode-based bridge type superconducting fault current limiters (SFCL) developed can only limit the tran- sient fault current, meanwhile the SCR-based bridge type SFCLs need up to ten milliseconds acting time to limit the steady fault current due to the inherent switching character of SCRs. To limit the fault current effectively and shorten the acting time to suit various power applications, this paper proposes a fully controlled hybrid bridge type SFCL using fast-response power electronic switches like MOSFETs and IGBTs. The circuit topology, con- trol strategy and theoretical modeling of the proposed SFCL are presented in details. A 220 V/1 kA SFCL case is conceptually designed to study the operational characteristics of the proposed SFCL, and to compare with the conventional diode-based and SCR-based SFCLs. The results show that the proposed SFCL has the advantages of fast response to suit both fault occurrence and power system recovery, and has favorable ability to limit both the transient and steady fault currents. Index Terms—Bridge type superconducting fault current lim- iter (SFCL), MOSFET, power electronics, superconducting coil, superconducting fault current limiter (SFCL), superconducting power system.

A unified energy exchange system with an equivalent dc circuit topology is presented for superconducting magnetic energy storage (SMES) study. The principle and experimental prototype design have been carried out to study the dynamic energy exchange characteristics of SMES for both voltage sag and swell compensations, with a new bridge-type I/V chopper and relevant digital control method introduced and compared with the conventional chopper. The bridge-type I/V chopper has been demonstrated to be more suitable for low-voltage power applications because of its high energy storage and exchange efficiencies. The integrated SMES application solutions and characteristics in the modern power systems have also been discussed using two sample cases of daily load leveling and voltage fluctuation compensation presented.

Objective The aim of this study was to quantitatively evaluate the relationship between short echo time pulmonary 1 H magnetic resonance imaging (MRI) signal intensity (SI) and 3 He MRI apparent diffusion coefficients (ADC), high-resolution computed tomography (CT) measurements of emphysema, and pulmonary function measurements. Materials and methods Nine healthy never-smokers and 11 COPD subjects underwent same-day plethysmography, spirometry, short echo time ((TE) = 1.2 ms) 1 H and diffusion-weighted hyperpolarized 3 He MRI ( b = 1.6 s/cm 2 ) at 3.0 T. In addition, for COPD subjects only, CT densitometry was also performed. Results Mean 1 H SI was significantly greater for never-smokers (12.1 ± 1.1 arbitrary units (AU)) compared to COPD subjects (10.9 ± 1.3 AU, p = 0.04). The 1 H SI AP-gradient was also significantly greater for never-smokers (0.40 AU/cm, R 2 = 0.94) compared to COPD subjects (0.29 AU/cm, R 2 = 0.968, p = 0.05). There was a significant correlation between 1 H SI and 3 He ADC ( r = −0.58, p = 0.008) and significant correlations between 1 H MR SI and CT measurements of emphysema (RA 950 , r = −0.69, p = 0.02 and HU 15 , r = 0.66, p = 0.03). Conclusions The significant and moderately strong relationship between 1 H SI and 3 He ADC, as well as between 1 H SI and CT measurements of emphysema suggests that these imaging methods and measurements may be quantifying similar tissue changes in COPD and that pulmonary 1 H SI may be used to monitor emphysema as a complement to CT and noble gas MRI.

Biodiesel fuels, made from renewable resources, have emerged as viable alternatives to conventional diesel fuel, but their impact on emissions is not fully understood. This study examines elemental carbon (EC), organic carbon (OC), and polycyclic aromatic hydrocarbons (PAHs) emissions from cottonseed oil biodiesel (CSO-B100). Relative to normal diesel fuel, CSO-B100 reduced EC emissions by 64% (±16%). The bulk of EC emitted from CSO-B100 was in the fine particle mode (

BACKGROUND AND AIM We previously reported that hypothermic machine perfusion (HMP) for liver preservation is feasible, but hepatic microcirculatory dysfunction and significant liver damage remain major obstacles in its application when the preservation is extended to 24 h. The underlying injury mechanism is not well understood. The present study sought to investigate the role of thromboxane A(2) (TXA(2)) in the pathogenesis of liver injury after prolonged HMP. METHODS Livers isolated from Sprague-Dawley rats were subjected to continuous machine perfusion with University of Wisconsin (UW) solution at a flow rate of 0.4 mL/min/g liver at 4 degrees C for 24 h. A specific TXA(2) synthase inhibitor, OKY-046 (OKY), was added to UW solution during the preservation period and to the Krebs-Henseleit buffer during reperfusion. The performance of the livers after preservation was evaluated using an isolated liver perfusion system with Krebs-Henseleit buffer at a flow rate of 15 mL/min at 37 degrees C for 30 min. RESULTS Prolonged HMP induced a significant release of TXA(2) into the portal circulation as indicated by markedly increased levels of TXB(2) in the perfusate during reperfusion (at 30 min, 1447.4 +/- 163.6 pg/mL vs 50.91 +/- 6.7 pg/mL for control). Inhibition of TXA(2) synthesis with OKY significantly decreased releases of TXA(2) (69.8 +/- 13.4 pg/mL) concomitant with reduced lactate dehydrogenase (LDH) releases (at 30 min, HMP + OKY: 144.9 +/- 27.9 U/L; HMP: 369.3 +/- 68.5 U/L; simple cold storage or SCS: 884.4 +/- 80.3 U/L), decreased liver wet/dry weight ratio (HMP + OKY vs SCS and HMP: 3.6 +/- 0.3 vs 4.4 +/- 0.1 and 3.9 +/- 0.2, respectively) and increased hyaluronic acid uptake (at 30 min, HMP + OKY vs SCS, HMP: 33.1 +/- 2.9% vs 13.9 +/- 3.6%, 18.6 +/- 2.4%, respectively). Liver histology also showed significant improvement in tissue edema and hepatocellular necrosis with OKY compared with HMP without OKY. CONCLUSION The results demonstrate that TXA(2) is involved in the development of hepatocellular injury induced by HMP, and inhibition of TXA(2) synthesis during preservation and reperfusion protects liver hepatocytes and sinusoidal endothelial cells from injuries caused by prolonged HMP.

Hypothermic machine perfusion (HMP) has the potential to improve recovery and preservation of Donation after Cardiac Death (DCD) livers, including uncontrolled DCD livers. However, current perfusion solutions lack the needed substrates to improve energy recovery and minimize hepatic injury, if warm ischemic time (WIT) is extended. This proof-of-concept study tested the hypothesis that the University of Wisconsin (UW) solution supplemented with anaplerotic substrates, calcium chloride, thromboxane A2 inhibitor, and antioxidants could improve HMP preservation and minimize reperfusion injury of warm ischemic livers. Preflushed rat livers subjected to 60 min WIT were preserved for 5 h with standard UW or supplemented UW (SUW) solution. Post preservation hepatic functions and viability were assessed during isolated perfusion with Krebs-Henseleit solution. Livers preserved with SUW showed significantly (p < .001) improved recovery of tissue ATP levels (micromol/g liver), 2.06 +/- 0.10 (mean +/- SE), as compared to the UW group, 0.70 +/- 0.10, and the level was 80% of that of fresh control livers (2.60 +/- 0.13). At the end of 1 h of rewarming, lactate dehydrogenase (U/L) in the perfusate was significantly (p < .05) lower in the SUW group (429 +/- 58) as compared to ischemia-reperfusion (IR) (781 +/- 12) and the UW group (1151 +/- 83). Bile production (microg/min/g liver) was significantly (p < .05) higher in the SUW group (280 +/- 13) as compared to the IR (224 +/- 24) and the UW group (114 +/- 14). The tissue edema formation assessed by tissue wet-dry ratio was significantly (p < .05) higher in UW group. Histology showed well-preserved hepatic structure in the SUW group. In conclusion, this study suggests that HMP with SUW solution has the potential to restore and preserve livers with extended WIT.

A Pb/Al codoped silica fibers were fabricated using atomic layer deposition (ALD) technique in combination with modified chemical vapor deposition (MCVD). PbO and Al 2 O 3 were induced into fiber core area by ALD. Faraday Effect of Pb/Al codoped silica fiber (PADF) was investigated for current sensor. Its Verdet Constant with 1 mm pitch was larger than 12% that of single mode fiber (SMF). It is very important for fiber-optic gyroscope and fiber-optic current sensors to optimize fabrication and design optical fibers, and to obtain relatively good magneto-optic sensitivity of optical fiber. This can be improved by Pb/Al codoped materials.

BACKGROUND Non-heart-beating donor (NHBD) livers are an untapped source with the potential to provide relief to the current donor shortage problem. Hypothermic machine perfusion (MP) has the potential to reclaim and preserve these marginal donor organs. METHODS This study compared 5-day survival in a rat NHBD liver transplantation model with simple cold storage (SCS) and MP-preserved tissues that had experienced 30 min of warm ischemia followed by a 5-hr preservation period with the University of Wisconsin solution. Total release of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were determined at major time points. Bilirubin levels and histology were examined after 5-day survival. RESULTS Six of seven control livers and five of six MP livers survived, whereas SCS tissues had survival in zero of seven. The results showed that MP livers had reduced release of LDH and ALT after 5 hr of storage, 5.07+/-1.42 and 2.02+/-0.69 U (mean+/-SE), respectively, compared with SCS, 15.54+/-0.81 and 3.41.3+/-0.73 U, respectively. Bilirubin values after 5-day survival of MP livers (1.17+/-0.49 mg/dL) were comparable to controls (0.91+/-0.36 mg/dL). Histology confirms that SCS displayed increased necrosis and MP tissue showed regions of near normal hepatic structure. CONCLUSIONS These results suggest that MP for 5 hr improves survival and reduces cellular damage of liver tissue that has experienced 30 min of warm ischemia when compared with SCS tissues. Further studies need to be conducted, but this study suggests that MP preservation has the potential to reclaim and preserve NHBD liver tissues.

Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A2(TXA2) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA2in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate. After 30 min of nonrecirculating perfusion, the buffer was recirculated in a total volume of 100 ml. The perfusate was sampled for the enzyme immunoassay of thromboxane B2(TXB2), the stable metabolite of TXA2. Although recirculation of the buffer caused no significant change in sham-operated rats, it resulted in a marked increase in portal pressure in BDL rats. The increase in portal pressure was found concomitantly with a significant increase of TXB2in the perfusate (sham vs. BDL after 30 min of recirculating perfusion: 1,420 ± 803 vs. 10,210 ± 2,950 pg/ml; P < 0.05). Perfusion with a buffer containing indomethacin or gadolinium chloride for inhibition of cyclooxygenase (COX) or Kupffer cells, respectively, substantially blocked the recirculation-induced increases in both portal pressure and TXB2release in BDL group. Hepatic detection of COX gene expression by RT-PCR revealed that COX-2 but not COX-1 was upregulated following BDL, and this upregulation was confirmed at the protein level by Western blot analysis. In conclusion, these results clearly demonstrate that increased hepatic TXA2release into the portal circulation contributes to the increased portal resistance in BDL-induced liver injury, suggesting a role of TXA2in liver fibrosis-induced portal hypertension. Furthermore, the Kupffer cell is likely the source of increased TXA2, which is associated with upregulation of the COX-2 enzyme.

Heme oxygenase (HO)-1 is up-regulated after ischemia/reperfusion and contributes to maintenance of hepatic perfusion and integrity. Blockade of HO-1 leads to an increased portal pressor response in the stress-exposed liver. We tested whether the increase in portal pressure reflects unmasking of a concomitant up-regulation of the vasoconstrictor endothelin (ET)-1. Hemorrhagic shock induced messenger RNAs encoding HO-1 (16-fold) and ET-1 (9-fold) with a similar time course in the liver. At maximum induction of both mediators, rats received either vehicle or the endothelin ET(A/B) antagonist bosentan (10 mg/kg intravenously). Subsequently, the HO pathway was blocked in all animals by tin-protoporphyrin (SnPP)-IX (50 micromol/kg intravenously). Portal and sinusoidal hemodynamics were measured using microflow probes and intravital microscopy, respectively. Blockade of the HO pathway led to a significant increase in portal resistance (sham/SnPP-IX, 0.17 +/- 0.046 mm Hg. min. mL(-1); shock/vehicle/SnPP-IX, 0.57 +/- 0.148 mm Hg. min. mL(-1); P

Background/Aims : Endothelin (ET) is one of the most active vascular regulators in the liver. It is unknown how partial portal vein ligation (PPVL) induced prehepatic portal hypertension influences the response of the liver to ET and its agonists. Therefore, this study was conducted to determine the expression of ET receptors and its functional significance after PPVL. Methods : Competitive receptor binding study and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed using liver homogenates after 2 weeks of PPVL or sham operation in rats. Hepatic microcirculation was evaluated in vivo using intravital microscopy. Results : Although there was no significant difference in dissociation constant ( K d ) and total amount of receptors ( B max ) between sham and PPVL, the proportion of ET B receptor was significantly increased in PPVL. RT-PCR analysis confirmed the up-regulation of ET B receptors demonstrated by the competitive receptor binding assay. In the functional study, infusion of ET B agonist (IRL 1620) in a low dosage did not change the hepatic microcirculation in sham but strongly constricted the sinusoids leading to a reduction of sinusoidal perfusion in PPVL. Conclusions : These results suggest that prehepatic portal hypertension may predispose the hepatic microcirculation to dysregulation in stress conditions where ET is upregulated.

The present study was undertaken to investigate hepatic microcirculatory response following partial portal vein ligation (PPVL) in rats. Portal pressure was markedly increased 2–6 wk after PPVL, but no significant reduction in sinusoidal perfusion and hepatocellular injury were detected. However, marked neovascularization was observed in PPVL rats using intravital microscopy and scanning electron microscopy (SEM). Extremely high red blood cell velocity (2,000–4,900 μm /s) was seen in these vessels. Injection of fluorescein sodium via the carotid artery revealed that the neovessels originated from the hepatic arterial vasculature. This was further confirmed by clamping the common hepatic artery and phenylephrine injection from the carotid artery. These vessels maintained sufficient flow after massive sinusoidal shutdown elicited by the portal infusion of endothelin receptor B agonist IRL-1620. SEM also showed extensive neovascularization at the hilum. Additionally, clamping the portal vein decreased sinusoidal perfusion only by 9.5% in PPVL, whereas a 71.2% decrease was observed in sham. These results strongly suggest that the liver maintains its microcirculatory flow by vascular remodeling from the hepatic arterial vasculature following PPVL.

Background Hypothermic machine perfusion preservation (MPP) has the potential to relieve the current donor shortage problem by providing superior preserved tissue and viable non-heart-beating donor tissue. For the liver, MPP has not improved preservation. Currently, the major cause of damage associated with MPP of livers is unknown. Methods. An intravital microscopy study was conducted to investigate the state of sinusoidal perfusion during MPP and the effect of a high potassium perfusion solution on liver microcirculation. Results. The results showed that there was an increase in vascular resistance (>200%) when the liver was perfused with a high K solution at either 37° or 5°C and with a flow rate of 14 or 5 mvmino Heterogeneous flow perfusion at the microcirculatory level was evident with regions of no-flow, which after a 10 hr MPP protocol remained unperfused during rewarming. These areas also displayed increased cellular injury as determined by propidium iodide staining (246.4 vs. 12.3 cells) compared with regions that were perfused during MPP. Conclusion. These results suggest that a heterogeneous flow pattern occurs during MPP of the liver as a result of the high K perfusion solution. Regions of no-flow during extended MPP remained unperfused during rewarming resulting in tissue damage and may represent a cause of liver damage associated with MPP.

This study was performed to determine whether ischemia/reperfusion (I/R) injury in rat liver results in alterations in endothelin receptor expression. Hepatic ischemia was produced in rats for 60 min followed by 6 or 24 h reperfusion. Portal inflow pressure was increased (7.38+/-0.60 mmHg) at 24 hours after reperfusion. Serum ALT increased significantly at both 6 and 24 h (6 h; 258.3+/-74.3, 24 h; 243.1+/-74.8 IU/L). Portal vascular response to an endothelin-B receptor agonist (IRL 1620) was significantly increased in the I/R livers compared to control and this was potentiated by L-NAME. IRL 1620 also caused LDH release from I/R livers but not controls. LDH release after IRL 1620 in I/R livers correlated with increased portal pressure response. To determine whether the altered response might be the result of altered endothelin receptor expression, livers were harvested after reperfusion and total endothelin binding sites were determined by competitive binding with ET-1. Proportion of endothelin receptor subtypes (ET(A)/ET(B)) was determined using the ET(A) antagonist BQ-610 (1 microM) and ET(B) agonist IRL-1620 (100 nM). There were no significant changes in Kd but Bmax for endothelin-1 was decreased in I/R group especially non-ischemic lobe at 24 h. ET(A) receptors were significantly decreased whereas ET(B) receptors were increased. These changes were more pronounced at 24 h after reperfusion than at 6 h. Interestingly, the changes in ET receptors was observed identically both in ischemic and non-ischemic lobes (ischemic lobe ET(A) 41.9%, ET(B) 51%; non-ischemic lobe ET(A) 38.8%, ET(B) 49.5%). These results indicate that the major functional endothelin receptor subtype upregulated in I/R is the ET(B) receptor and that this upregulation may contribute to microvascular dysregulation and hepatic injury.

We determined the role of nitric oxide (NO) and endothelins (ETs) in the regulation of hepatic blood flow during resuscitation from hemorrhagic shock (HS) in anesthetized rats. Volume resuscitation restored systemic hemodynamics and increased hepatic arterial and portal venous flow above baseline in the vehicle group. Presence of N omega-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) during resuscitation increased systemic vascular resistance (SVR) above baseline, prevented the restoration of hepatic arterial flow, and abolished portal hyperemia. Although the ETA+B-receptor antagonist bosentan (10 mg/kg) did not alter the systemic hemodynamic response, it abolished the hepatic arterial and portal hyperemia. The ETA-receptor antagonist BQ-610 (150 micrograms/kg) reduced SVR below baseline, allowed hepatic arterial hyperemia to occur, and further enhanced the portal venous hyperemia. This indicates that 1) NO reduces SVR and acts to preserve hepatic blood flow during resuscitation from HS; 2) ETA-receptor-mediated vasoconstriction counteracts the systemic and portal hemodynamic effects of NO; and 3) simultaneous ETB-receptor stimulation enhances blood flow to the liver and may serve to modulate the ETA-receptor-mediated vasoconstrictive effects of ETs.

CCL3 is a C-C family chemokine detected at high levels in the synovial tissue and fluids of rheumatoid arthritis (RA) patients. CCL3 binds to the chemokine receptors CCR1 and CCR5, which are expressed by inflammatory leukocytes such as macrophages and T cells present in the affected joints of RA patients. The present study was undertaken to investigate whether absence of CCL3 prevented development of inflammation and joint destruction in anti-type II collagen monoclonal antibody (anti-CII mAb)-induced arthritis. "CCL3 null mice were different from wild-type control mice in terms of body weight loss". In addition, CCL3 null mice exhibited milder clinical and histopathological scores following administration of anti-CII mAb and endotoxin. Moreover, the release of TNF in response to systemic administration of endotoxin was not affected in CCL3 null mice compared to wild-type mice, indicating that the phenotype was not attributable to a defect in endotoxin response. These results indicate that CCL3 plays an essential role in the development of inflammation and joint destruction induced by anti-CII mAb.

A general purpose full-wave electromagnetic simulator IE3-D has been developed for the analysis and design of high-frequency and high-speed electronic circuit structures. For an arbitrarily shaped 3-D metallic layered structure, the integral equation, and method of moment-based simulator solves the current distribution on the structure expanded into roof-top functions on a set of 3-D triangular and rectangular cells. The circuit parameters are extracted from the solved current distribution in the form of either S-parameters frequency response and RLC-equivalent circuit in SPICE format. >

Primary idiopathic chylopericardium is a rare disease, particularly in children. We report the case of a 5-year-old male child who presented with cough and dyspnoea. Bulging of the chest wall and distant heart sounds suggested the diagnosis of a pericardial effusion, which was confirmed on a chest computed tomography. Pericardial drainage confirmed the diagnosis of a chylopericardium. After the failure of continuous catheter drainage, surgical ligation of the thoracic duct and the creation of a pericardial window were performed under thoracoscopy.

An improved SMES circuit topology is proposed for improving the energy storage and discharge efficiencies. The switching control principle of the improved SMES circuit topology is presented in detail with an experimental HTS coil switching control system designed. The results obtained verify that the control system is favorable for charging, storing and discharging the magnetic energy in an HTS coil of a SMES system.

This paper presents the worldwide developments of superconducting magnetic energy storage (SMES) devices. The application solutions of SMES technology for future smart grids are further discussed. The application topologies and advantages of SMES for micro grids, transmission and distribution systems are briefly described. The application scheme of hybrid energy storage systems (ESSs) and distributed SMES (D-SMES) devices are proposed and discussed to combine the advantages from small-scale SMES devices and other conventional ESSs, and to achieve better performance in practical power applications. Finally, the integrated solutions for smart grids are proposed, and the basic functions and application schemes of SMES devices are initially presented and discussed.

A general purpose CAD tool, the IE3D electromagnetic simulator is presented in this article. The simulator is based on an integral equation, a method-of-moment formulation for a full-wave solution of three-dimensional (3D) arbitrarily shaped structures in microwave and millimeter-wave integrated circuits (MMIC), high temperature superconductor (HTS) circuits, microstrip antennas, RF printed circuit boards (PCB), and high speed digital circuit packaging. The primary solution of the simulator is the current distribution on a metallic structure in an environment of multilayered substrates on infinitely extended ground plane. The circuit parameters of the structure in either S-parameter form or RLC-SPICE equivalent circuit form is extracted from the solved current distribution. The simulator consists of an MS-Windows-based layout editor, a schematic editor, an electromagnetic simulator, and a post processor. The simulator can perform stand-alone electromagnetic simulation and optimization and mixed electromagnetic and nodal analysis. Simulation results for structures in various high frequency and high speed domains are presented and compared to measured results. © 1994 John Wiley & Sons, Inc.

Objective: The aim was to determine if lactosylphenyl Trolox could improve myocardial resistance to ischaemia and reperfusion. Lactosylphenyl Trolox is derived by coupling p-aminophenyl-β-D-lactopyranoside to Trolox. Trolox, a polar analogue of vitamin E, has been found to protect human cardiomyocytes against oxyradicals and to reduce myocardial damage by 66% in a canine ischaemia-reperfusion model. Methods: New Zealand white rabbits (weighing – 3.5 kg) were subjected to 1 h ischaemia by ligation of the main branch of the anterior ventricular coronary artery. Approximately 1-2 min before release of ischaemia, a 30 ml bolus of saline (placebo control) or saline containing lactosylphenyl Trolox was injected into the right external jugular vein, followed by 3 h reperfusion. The area at risk was identified by staining with Evans Blue. Area of necrosis was indicated by tetrazolium red staining, confirmed by histopathology and quantified by planimetry. Results: The control group (n=6) had 46.6(SD 10.0)% necrosis of the area at risk but the lactosylphenyl Trolox treated groups (n=6 per group) had reduced necrosis: 24.0(6.5)%, 17.4(8.2)%, and 6.9(3.6)% at doses of 2.5, 5.0, and 10 μmol·kg−1, respectively (each with p < 0.05 v control value). These translated to 48.6(14.0)%, 62.7(17.6)%, and 85.3(7.8)% myocardial salvage, respectively. In contrast, the salvages achieved with 2.5 and 10 μmol·kg−1 of Trolox were 31.0(11.0)% and 62.1(18.9)% respectively (both p < 0.05 v lactosylphenyl Trolox). Conclusions: Lactosylphenyl Trolox reduces myocardial infarct size more effectively than Trolox in a rabbit model of ischaemia-reperfusion. Cardiovascular Research 1993; 27 :736-739

This paper investigates the performance of a prototype resistive fault current limiter (FCL) made using a high temperature superconductor (HTS). Its behavior under normal operation and short-circuit conditions in a 6 kV/1 kA power system is analyzed with regard to the feasibility of using this HTS FCL device in electrical power systems. © 2007 Elsevier B.V. All rights reserved.

Background and Aim: Partial portal vein ligation (PPVL) is a commonly used procedure to induce prehepatic portal hypertension in animal models. The aim of this study was to test the hypothesis that the hepatic arterial flow becomes the primary source feeding the sinusoids in the liver after PPVL. Methods: Sprague–Dawley rats underwent either sham operation or partial portal vein ligation (PPVL). The number of vessels in the liver at 2 weeks postoperatively was determined by factor VIII immunolocalization and the gene expression of angiogenic factors was assessed by RT-PCR. The total hepatic arterial supply to the liver was measured using the fluorescent microsphere injection technique. To further test the hypothesis, two additional groups of rats underwent hepatic artery ligation (HAL) or PPVL plus HAL (PPHAL). The integrity of hepatic microcirculation was then evaluated in all four groups by intravital microscopy. Results: At 2 weeks after operation, the number of vessels detected by factor VIII staining was significantly higher in PPVL compared to sham. Densitometric analysis of RT-PCR bands revealed a significant increase of vascular endothelial growth factor gene expression in PPVL compared to sham. Arterial flow to the liver measured by fluorescent microspheres was increased by 190% in PPVL compared to sham. When all four groups were compared, no prominent histological abnormality was observed in sham, HAL, and PPVL groups; however, PPHAL livers showed focal necrosis and inflammatory cell infiltration around the portal triads. Additionally, only the PPHAL livers showed a decreased sinusoidal diameter and significantly lower perfusion index (PPHAL 42.9 ± 6.1; sham 85.7 ± 7.0, PPVL 80.2 ± 6.5, HAL 70.9 ± 4.5). Conclusions: These results suggest that the hepatic artery flow becomes the primary source for the blood supply of sinusoids and the compensatory change in the hepatic arterial system plays a critical role in maintaining microcirculatory perfusion following the restriction of the portal vein flow by PPVL.

Background/Aims Thromboxane A 2 (TXA 2 ) has been suggested to play a significant role in the development of portal hypertension in fibrosis, and Kupffer cell (KC) derived TXA 2 has been shown to mediate the hyperresponsiveness of the portal circulation to the vasoconstrictive actions of endothelin-1 (ET-1) during endotoxemia. The aim of this study was to determine whether the double stresses of prefibrotic changes and endotoxemia additively activate KC to increase release of TXA 2 in response to ET-1, resulting in elevated portal resistance. Methods One week Bile duct ligation (BDL) rats and sham-operated controls were subjected to isolated liver perfusions following LPS or saline for 6h. In a separate experiment, KC were isolated from BDL or sham rats and incubated with LPS or saline for 6h before the ET-1 treatment. Results The double stresses of early fibrosis and LPS resulted in a greater sustained increase in portal pressure in response to ET-1 in BDL rats, and this increase correlated well with the much enhanced release of TXA 2 in the perfusate. Media from the cultured KC showed significantly greater TXA 2 release in response to ET-1 in BDL group than those in sham group, and LPS exacerbated this effect. Protein levels of cytosolic phospholipase A 2 (cPLA 2 ), cyclooxygenase-2, and thromboxane synthase were also significantly elevated in KC from BDL rats. ET-1 produced a marked increase in cPLA 2 activation as measured by the phosphorylation of cPLA 2 in KC of both BDL and sham groups. LPS greatly exacerbated the activation of cPLA 2 . Conclusions The data suggest that the double stresses additively activate KC with an upregulation of the key enzymes in the TXA 2 biosynthesis and release increased amount of TXA 2 via the augmented activation of cPLA 2 in response to ET-1, which leads to the increased portal resistance and ultimately hepatic microcirculatory dysfunction.

This study addresses the microvascular mechanisms by which a remote, mild stress such as blunt trauma sensitizes the liver to injury. Rats received closed femur fracture (FFx), and 24 h later livers were isolated and perfused at a similar starting flow rate for assessment of vascular response to endothelin-1 (ET-1). Sinusoidal volumetric flow (QS), red blood cell velocity (VRBC), and sinusoidal diameter (Ds) were determined by intravital microscopy. Baseline portal resistance in livers from FFx rats was not changed. The FFx group showed a lower baseline VRBC (322.9 +/- 26.4 and 207.3 +/- 17.2 microm/s in sham and FFx,) and QS (28.4 +/- 4.2 and 17.6 +/- 2.1 pL/s in sham and FFx, P < 0.05). ET-1 caused a decrease in the VRBC in sham but no change after FFx. In contrast, Ds was unchanged by ET-1 in sham but decreased in FFx (10.3 +/- 0.4 to 10.7 +/- 0.5 vs. 10.6 +/- 0.4 to 9.0 +/- 0.4 microm at 10 min in sham and FFx groups, P < 0.05). The overall result of these changes was a greater decrease in sinusoidal flow in FFx compared with sham. There was no significant change in mRNA for ET-1, endothelin A (ETA) receptor, or iNOS (inducible nitric oxide synthase) in FFx compared with sham. However, endothelin B (ETB) receptor mRNA and eNOS (endothelial nitric oxide synthase) mRNA were increased in the FFx group (ETB, 54.81 +/- 8.08 in sham vs. 83.28 +/- 8.19 in FFx; eNOS, 56.11 +/- 2.53 in sham vs. 83.31 +/- 5.51 in FFx; P < 0.05) while the levels of these proteins remained unchanged. Caveolin-1 (cav-1) protein levels were elevated in FFx, and coimmunoprecipitation with both ETB and eNOS showed increased associations with these proteins, suggesting a possible inactivation of eNOS. The eNOS activity was also blunted in FFx animals in the presence of increased cav-1 expression. Taken together, these results demonstrate that remote trauma sensitizes the liver to the sinusoidal constrictor effect of ET-1. We propose that this hyperresponsiveness occurs as a result of uncoupling of the ETB receptor from eNOS activity mediated by interaction of eNOS and possibly the ETB receptor with increased caveolin-1. This vascular sensitization that occurs after FFx may contribute to the exacerbation of injury during subsequent stresses.

BACKGROUND Although hypothermic machine perfusion (HMP) preservation has been shown to improve organ function and to expand the organ donor pool, problems still exist with the current HMP technology for liver preservation. The present study was conducted to investigate endothelial and hepatocellular functions following extended HMP (> r =24 hr) in rat liver model. METHODS Following 24-hour hypothermic HMP with University of Wisconsin (UW) solution or 24-hour simple cold storage (SCS), livers were reperfused with Krebs-Henseleit buffer solution at 37 degree C for 30 minutes. Hepatocyte damage and function were assessed by measuring lactate dehydrogenase (LDH) activity, bile production, and indocyanine green (ICG) extraction. Sinusoidal endothelial cell (SEC) function and permeability were determined by hyaluronic acid (HA) uptake and multiple indicator dilution (MID) method, respectively. RESULTS After 24-hour hypothermic preservation, HMP livers showed lower released LDH levels, higher bile flow rate, and greater hepatic ICG uptake compared with SCS livers. However, LDH levels became significantly higher in HMP than in SCS after 30 minutes of warm perfusion. The increased enzyme levels were accompanied by a significant increase in endothelial permeability to albumin and a decrease in hyaluronic acid uptake in HMP compared to SCS. Liver wet/dry weight ratio confirmed a greater edema in HMP livers than SCS livers. CONCLUSION These results suggest that 24-hour hypothermic HMP may help preservation of hepatocyte function, but endothelial cell dysfunction during the cold preservation may play a key role in hepatocyte dysfunction and parenchymal cell death upon reperfusion.

The shortage of donor organs for liver transplantation requires investigations into expanding the donor pool. Non-heart beating donor (NHBD) livers are an untapped source of organs. NHBD organs are those that have had a period of warm ischemia prior to cold preservation. A main concern of NHBD livers is that there is a depletion of energy stores during the warm ischemia and subsequent cold storage. This study is to investigate the use of hypothermic machine perfusion to regenerate energy stores in the liver during 5hr storage and after 1hr rewarming in a rat transplantation model. Results will be compared with control. (no warm ischemia) and simple cold stored tissues.Copyright © 2003 by ASME

Background Hypothermic machine perfusion preservation has the potential to relieve the current donor shortage problem by reclaiming and preserving marginal donor organs including those from viable non-heart-beating donors. A number of problems exist with the current machine perfusion technology for preserving livers, and much research is needed to determine the clinical impact of this technology in preserving non-heart-beating donor livers. Methods This study was conducted to compare the poststorage function and microcirculation of simple cold stored and machine perfusion preserved livers that had experienced 30 min of warm ischemia followed by a 10 hr preservation period. In an isolated rat liver perfusion model, lactate dehydrogenase activity, indocyanine green secretion, and portal pressure values were determined at major time points. An intravital microscopy was conducted to assess microcirculation. Results The results showed an increase in flow homogeneity of machine perfused livers, which correlated with the reduction in portal pressure when compared with simple cold storage (5.4+/-0.4 vs. 8.7+/-0.6 mm Hg). A reduction in lactate dehydrogenase levels in the perfusate (333+/-22 vs.103+/-8 U/L) and an increase in bile production of the machine perfused livers (4.9+/-0.5 vs. 33.2+/-1.7 microg/min/g liver) and indocyanine green secretion (11.7+/-1.7 vs. 21.2+/-2.1 Abs/g bile) were observed at all time points (mean+/-SE of final point given). Intravital microscopic examination indicated that large regions of non flow, as indicated by the absence of fluorescein isothiocyanate-labeled albumin, were observed in the simple cold stored tissue, whereas machine perfused liver showed increase flow homogeneity. Values of bile production, indocyanine secretion, and cellular damages were comparable with controls. Histologic examination confirmed that simple cold stored tissue displayed increased vacuolization, and machine perfused tissue showed regions of normal hepatic structure. Conclusion These results suggest that machine perfusion for 10 hr improves both poststorage function and microcirculation while reducing cellular damage of liver tissue that has experienced 30 min of warm ischemia, when compared with simple cold storage. Further studies need to be conducted, but this study suggests that machine perfusion preservation has the potential to reclaim and preserve liver tissues after warm ischemic insult.

The rat is increasingly being used to study the physiological response to elevated intra-abdominal pressure (IAP) during laparoscopic surgery. Although decreased portal venous flow associated with the elevated IAP has been reported in large animals, little information is available in rats. Furthermore, the relative blood flow changes in the hepatic artery and portal vein have not been reported. Therefore, this study was performed to elucidate the change in systemic and splanchnic circulation, including hepatic arterial and portal venular flow, during pneumoperitoneum in rats. Sprague–Dawley rats were assigned into either a ventilated or nonventilated group and then subjected to various levels of IAP (0, 5, 10, and 20 mm Hg) using carbon dioxide gas. At each pressure, both cardiac output and splanchnic organ flow were determined using fluorescent microspheres. There was no obvious hemodynamic difference between the ventilated and nonventilated groups. Mean arterial pressure and cardiac index were significantly lower with 20 mm Hg of IAP compared to 0 mm Hg in both groups. Flow to the spleen, stomach, duodenum, total intestine, and portal vein was all decreased by increasing IAP (P < 0.05 at 20 mm Hg compared to 0 mm Hg) and was significantly correlated to the decrease in cardiac index. However, the hepatic arterial flow was relatively preserved throughout all levels of IAP, suggesting activation of the hepatic arterial buffer response. We conclude that the decreased splanchnic flow during pneumoperitoneum largely depends on the decreased cardiac index. Hepatic artery flow, however, is selectively preserved and may provide protection for liver function during sustained elevations in IAP.

Oxidative stress and inflammatory reactions associated with stresses that may lead to shock promote hepatic microcirculatory dysfunction, which may lead to hepatic injury. Because altered liver microcirculation may result from an imbalance in the expression of stress-induced vasoactive mediators, our study was conducted to investigate changes in the expression of genes encoding endothelin-1 (ET-1), its receptors, ET(A) and ET(B), heme-oxygenase 1 (HO-1), and inducible nitric oxide synthase (iNOS), using two different rat models of liver stress: ischemia/reperfusion of the liver and lipopolysaccharide (LPS)-induced endotoxemia. In ischemia/reperfusion experiments, rats were subjected to 1 h hepatic ischemia, followed by 6 h of reperfusion. Endotoxemia was induced by i.p. injection of LPS (1 mg/mL/kg body weight); rats were studied after 6 h. mRNA levels were estimated using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on total RNA samples prepared from experimental and sham control rat livers. In the ischemic reperfused livers the levels of mRNA for ET-1, ET(B), HO-1, and iNOS were significantly elevated. The fold increase versus sham was 2.5+/-1.1 (ET-1), 2.1+/-1.3 (ET(B)), 2.1+/-.8 (HO-1), and 6.4+/-3.9 (iNOS). In contrast, the expression of ET(A) receptor gene was reduced after ischemia/reperfusion (to 73+/-1% of sham). In the separate experiments we analyzed the same mRNAs levels after 1 h of ischemia (no reperfusion), and did not detect any changes. During endotoxemia we observed a marked increase in iNOS mRNA level (>24-fold), as well as a marked elevation of the other four mRNAs. The fold increase versus sham was 6.1+/-1.7, ET-1); 1.5+/-.3 (ET(A)); 1.6+/-.4 (ET(B)); and 2.4+/-.34 (HO-1). These results show that liver stress, induced by ischemia/reperfusion or LPS injection have characteristic patterns of vasoregulatory genes expression indicating that, although both stresses result in an increase in specific vascular reactivity, different pathways are involved in inducing the hepatic vascular stress response.

High temperature superconducting (HTS) current leads (CLs) have become suitable for practical applications. Optimization of their performance based on different techniques will be the focus for further development of the applicable HTS CLs. Different types of HTS CLs are compared and analyzed with regard to achieving better properties for practical applications, especially to reduce the thermal conductivity by introducing different sheath alloys.

Distributed generation is expected to play an important role in the future with growth in electric load, enhancing economical efficiency and protection of the environment. Energy storage technology is one of the effective methods to ensure the quality of the electrical power supply and the effective operation of the distributed generation systems. In this paper, several main energy storage technologies are compared with regard to their performances. Especially the use of high temperature superconducting (HTS) energy storages, i.e. in forms of superconducting magnetic energy storage and flywheel energy storage, will be analyzed with regard to the device performances in distributed generation systems.

DC power transmission systems are considered to be developed using high-temperature superconductors (HTS) with advantages of higher current carrying capability, energy loss reduction, lower system voltages, high stability with self-protection, and more compact systems. This paper will provide technical assessments of HTS DC electrical power transmission systems using HTS techniques, and analysis of the system performance in steady and dynamic states will also be presented.

High T c superconductors (HTS) such as Bi-2223/Ag wires can be used to build inductors. Q value of the inductor made using HTS technology can be dramatically increased with readily cryogenic systems. This HTS inductor brings an electronic resonate circuit with special characteristics to have a wide range control of its voltages and currents which can achieve substantial values. The operation principle of the HTS resonator will be discussed in theory with experimental verification presented in this paper.

Although there is substantial evidence suggesting that the integrity of the microcirculation is an important determinant of tissue viability during reperfusion after ischemia in the liver, as well as other tissues, the mechanisms responsible for microvascular failure are not fully understood. It is now recognized that the microvascular response to reperfusion, similar to the whole organism response to shock, can consist of either a rapid exacerbation of injury after a severe ischemic episode or, alternatively, a more slowly developing alteration in responsiveness that occurs after a less severe insult. In the more slowly developing response, the alterations in vascular status are the result of up-regulation of stress-induced vascular mediators such as endothelin, nitric oxide synthase (NOS), and heme oxygenase, as well as changes in the reactivity of the effector cells to the mediators. The mechanisms for change in reactivity of vascular cells range from changes in receptor expression to overt phenotypic transformation, as can occur in the hepatic stellate cells in response to repeated injury. When maintained in balance, these counteracting constrictor and dilator influences can be protective; however, local imbalance can result in focal ischemia, thus propagating the injury. Thus, the remodeling of the hepatic microvascular responsiveness during reperfusion after ischemia may serve as a useful paradigm for consideration of the overall response of the organism to shock.

Heme oxygenase (HO)-derived carbon monoxide (CO) may contribute to vascular control through elevation of guanosine 3',5'-cyclic monophosphate. In the present study, we investigated the functional significance of expression of the isoenzyme HO-1 (heat-shock protein 32) in liver after hemorrhage/resuscitation (H/R) in rats anesthetized with pentobarbital sodium. An increase of mRNA levels for HO-1 was observed at 3 h after resuscitation, followed by induction of the protein at 6 h in pericentral hepatocytes and sinusoidal lining cells. Concomitantly, lower portal resistance was observed in H/R (0.33 +/- 0.060 mmHg.ml-1.min) compared with control rats (0.47 +/- 0.035 mmHg.ml-1.min). Blockade of the HO-CO pathway by tin protoporphyrin-IX (SnPP-IX) led to a transient increase in portal pressure with no effect on portal low in controls, whereas an increase in pressure and a decrease in flow contributed to the sustained increase in portal resistance after H/R. These results indicate that HO contributes to maintenance of hepatic perfusion in vivo under stressful conditions, suggesting a functional link between stress response and vascular control in portal circulation.

Although the deleterious effect of chronic ethanol consumption on subsequent stressful events has long been recognized, the pathophysiological mechanisms are incompletely understood. This study tested whether chronic ethanol consumption in doses that increase sinusoidal contractility increases susceptibility to hepatic microvascular failure and liver injury after hemorrhagic shock. Liver microcirculation was assessed by in vivo microscopy during hemorrhage and up to 24 h after onset of resuscitation and was compared with liver histology and serum enzyme levels. Mean sinusoidal blood flow was neither impaired by chronic ethanol feeding at baseline nor during hemorrhage and early resuscitation. However, failure of individual sinusoids to conduct flow was observed more frequently after fluid resuscitation in ethanol-fed animals (e.g., at 1 h after onset of volume therapy: 26% of sinusoids) than in controls (11%), reflecting substantial flow heterogeneity. Failing sinusoids had substantially smaller diameters than sinusoids conducting flow with a more profound and sustained response in ethanol-fed rats. At 24 h marked pericentral necrosis and increase in serum alanine aminotransferase levels were observed in six of nine surviving ethanol-fed animals but only in 1 of 10 pair fed controls and correlated with microvascular failure. These data suggest that early as well as late microvascular failure in this model of hemorrhagic shock and resuscitation is primarily mediated at the level of individual sinusoids. Chronic ethanol feeding exacerbates microvascular and hepatocellular injury after shock/resuscitation, probably involving increased sinusoidal contractile responsiveness.