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1.
Background : The effects of hypothermic injury to the liver were investigated on an isolated perfusion circuit by comparing porcine livers with varying degrees of preservation injury. Methods : A group of unstored livers (n= 5) were compared to livers stored in University of Wisconsin (UW) solution for 18 h (n= 5), and a group of livers stored in Hartmann's solution for 18 h (n= 5). Results : We observed that the degree of platelet sequestration was directly related to the severity of the preservation injury. After 2 h of isolated liver perfusion, the perfusate platelet count fell from 148 ± 14 × 109/L to 84 ± 13 × 109/L for control livers. In comparison for livers stored in UW solution, the platelet count fell from 173 ± 43 × 109/L to 61 ± 14 × 109/L, representing a 64.8% fall, while for those stored in Hartmann's solution, an even more profound fall from 152 ± 36 × 109/L to 19 ± 9 × 109/L (87.5% fall) was observed. The difference between the UW-stored and Hartmann's-stored livers was significant (P < 0.05). However, using this model, the degree of leukocyte sequestration did not differentiate the groups. Both histological and ultrastructural examination of liver biopsies taken immediately following revascularization demonstrated that for mild degrees of preservation injury following hypothermic storage, changes occur to the sinusoidal lining cells well before changes to the parenchymal elements. Conclusions : These findings substantiate the hypothesis that the primary injury associated with hypothermia involves the sinusoidal lining cells (non-parenchymal elements), that it is predominantly a reperfusion phenomenon and that efforts at improving preservation should therefore be targeted primarily at these cells and not the hepatocytes.  相似文献   

2.
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 (μ mol/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 (μ g/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.  相似文献   

3.
The University of Wisconsin (UW) solution consists of a relatively complex mixture of agents. In this study we compared simpler preservation solutions, namely, histidine-tryptophan-ketoglutarate glutarate (HTK) and phosphatebuffered sucrose (PBS) with different compositions of UW solution in the isolated perfused rabbit liver model. Livers were stored cold for 24 and 48 h. After 24 h of preservation, the amount of bile produced in UW-preserved livers was significantly greater (P<0.05) than that in HTK-preserved livers. Also, there was less LDH released into the perfusate in UW-preserved livers. There was more edema and lower K+/Na+ rations in HTK-preserved livers than in UW-preserved livers (all data P<0.05). After 48 h of preservation, the differences between livers preserved in UW or HTK solution were less noticeable than at 24 h and bile production was similar. LDH and AST release were greater in HTK-preserved livers than in UW livers, but these differences were not statistically significant. Preservation in PBS for 48 h was worse than in either UW or HTK solution. Substitution of polyethylene glycol (PEG) for hydroxyethyl starch (HES) in 48-h UW-preserved livers was not effective. We conclude that solutions simpler in composition than UW solution may be effective in kidney transplantation but do not appear suitable for successuful liver preservation.  相似文献   

4.
Severe microcirculatory disturbances due to endothelial cell damage and leukocyte adherence during reperfusion of transplanted livers are considered to contribute to early graft failure. Since the degree of reperfusion injury after liver transplantation depends on the length of preservation time and the solution used for preservation, the aim of our study was to assess three solutions with respect to microvascular perfusion and leukocyte adhesion. Therefore, rat livers were stored up to 24 h in Euro-Collins (EC), University of Wisconsin (UW), or histidin-tryphtophan-ketoglutarate (HTK) solutions prior to orthotopic transplantation. The livers were studied in situ 60 min postoperatively using intravital fluorescence video microscopy. Using simple syringe flushing (10 ml), sinusoidal perfusion decreased below 50% in EC preserved livers after 8 h preservation, in HTK preserved livers after 16 h preservation, and remained higher than 70% in livers preserved in UW up to 24 h. Permanent adhesion of leukocytes was increased more rapidly in organs after 1, 8, 16, and 24 h preservation in HTK (16%, 15%, 34%, and 49.7% ± 4.7%) compared to those preserved in UW (15%, 18%, 17%; and 32.7% ± 3.3%; P < 0.05). Using a 10-fold volumn of the organ weight of HTK solution during the harvesting procedure, with an 8 min equilibration period, sinusoidal perfusion (39.6 ± 4.7%) and leukocyte adhesion (42.7 ± 3.1%) were not improved after 24 h. In contrast, equilibration with a volumn of approximately 40-times the liver weight improved sinusoidal perfusion (70.8% ± 2.7%; P < 0.01) and leukocyte adhesion (24.9% ± 3.1%; P < 0.01) significantly. Thus, using HTK solution, simple flushing prior to long-term cold storage resulted in microcirculatory disturbances when compared to UW solution. Larger volumns of HTK solution with an additional equilibration period of 8 min, however, reduced leukocyte adhesion and improved sinusoidal perfusion to a similar degree as UW solution.  相似文献   

5.
HX—3液和UW液保存大鼠肝脏效果的比较   总被引:7,自引:1,他引:6  
采用大鼠肝脏非循环离体灌注模型比较自制的HX-3液和UW液对大鼠肝脏的保存效果。实验结果显示,经HX-3液原位灌洗并保存48小时的肝脏肝组织含水量正常,而同等条件下换用UW液,肝组织的含水量虽无明显变化,但都低于正常值;随着保存时间的延长,两组肝窦内皮细胞死亡率逐渐上升,但在24小时以内两组肝窥内皮细胞死亡率的差异不显著.  相似文献   

6.
An ex vivo isolated perfused porcine liver model was tested to assess its suitability for rapid, reliable and relatively cheap testing of organ preservation solutions for liver transplantation. The model consists of a machine driven recirculating system incorporating an organ chamber. blood pump and membrane oxygenator. Autologous blood was used for perfusion for a period of 2 h at a temperature of 37°C. The model was tested with five groups of livers which had sustained varying degrees of injury ranging from minimally damaged to those known to be incapable of sustaining life when used for liver transplantation. The groups of livers were: (i) controls; (ii) preserved in University of Wisconsin solution (UW) for 6 h; (iii) preserved in an albumin-based extracellular fluid (ALB) for 6 h; (iv) preserved in UW for 18 h; and (v) preserved in ALB for 18 h. Bile production was found to be a reliable parameter of preservation damage. Changes in perfusate levels of aspartate aminotransferase, potassium, glucose and calcium also occurred in relationship to preservation damage. In contrast, weight gain of the liver, sequestration of the white cells and platelets in the liver. urea production and oxygen consumption were unreliable predictors of liver damage. Histology of biopsy specimens revealed apparently well preserved livers in all cases after preservation but before perfusion, but serious abnormalities after perfusion in long preserved livers, with features in these suggestive of damage to the sinusoidal endothelium. We believe that the model is a worthwhile adjunct to research into liver preservation.  相似文献   

7.
We investigated the effect of donor pretreatment with chlorpromazine (CPZ), in rabbit livers cold-stored in University of Wisconsin (UW) cold storage solution for 48 hr. Three groups of livers were investigated: livers flushed with Perfadex and immediately thereafter reperfused on an isolated circuit (controls), and livers cold stored in UW solution for 48 hr, with or without donor pretreatment with CPZ, 3 mg/kg. After preservation, reperfusion was performed in vitro, using an isolated circuit (IPL). The reperfusion medium consisted of an oxygenated Krebs-Henseleit bicarbonate solution supplemented with 5 mM glucose, 50 mg/L of streptomycin and penicillin G, and 3.5% Dextran 60 for oncotic support. Livers that were not pretreated with CPZ produced 5.3 +/- 1.2 ml bile/100 g (mean +/- SD) during 2 hr of IPL reperfusion. CPZ donor pretreatment significantly improved the bile flow to 17.1 +/- 6.9 ml (P less than 0.01, Wilcoxon). This figure was not different from that in control livers without a storage period (18.3 +/- 3.8 ml). Alanine aspartate aminotransferase (ASAT) released into the perfusate was measured, and levels were increasing during 2 hr of reperfusion. ASAT values were moderately increased in the preserved groups compared with controls (P less than 0.01), with no discernible differences between livers with and without CPZ pretreatment. It is concluded that CPZ pretreatment of the donor improves preservation quality, as evidenced by improved bile formation. The present results suggest that 48 hr cold storage in UW solution may be safe for clinical preservation, if donors are pretreated with chlorpromazine.  相似文献   

8.
Integrity of the hepatic microcirculation and maintenance of endothelial cell viability are critical components in preventing primary non-function after liver transplantation. Therefore, hepatic microcirculation and leucocyte-endothelial interaction were studied in rat livers stored for 1 h in Euro-Collins (EC), University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solutions and subsequently transplanted. One hour after transplantation surgery, the livers were exposed under an intravital fluorescence microscope. After injection of the leucocyte marker acridine orange (1 mol/kg), six pericentral fields were observed for 30 s and experiments were recorded continuously. The percentage of perfused sinusoids was reduced in the livers in the EC group (82.9%) in contrast to the UW (93.2%) and HTK groups (91.0%). Livers in the EC group showed a reduction in the diameters of pericentral sinusoids (7.3±0.2 m; mean±SEM) compared with the UW group (9.5±0.2 m; P<0.05) and HTK group (10.2±0.8 m; P<0.05), indicating substantial cell swelling in livers stored in EC solution. Permanent adherence of leucocytes was most frequently observed in the EC group (33.5±1%), while this phenomenon was less pronounced in the UW group (14.5+1.1%; P<0.05) and HTK group (16.3±0.7%; P<0.05). Conversely, temporary adherence of leucocytes was reduced in the EC group (19.7+1.3%) compared with the UW group (30.5+2.1%) and the HTK group (34.4+0.8%). Microcirculatory failure and cell swelling in the EC group might be due to the lack of osmotic substances or oxygen radical scavengers included in UW (allopurinol, glutathione) and HTK (mannitol) solutions. In conclusion, cold storage of livers in UW and HTK solutions results in better preservation of the microcirculation and prevention of adhesion of leucocytes after transplantation compared with the EC solution.  相似文献   

9.
We used the isolated perfused rat liver model (IPRL) to assess parenchymal and nonparenchymal cell integrity after different conditions of storage and reperfusion. Two studies were performed. In study 1, the IPRL was applied to evaluate the effects of 30 min of normothermic reperfusion with Elohes solution, enriched William's medium (Wif), or Carolina rinse solution (CRS) following 24 h of cold preservation in high-K+ or high-Na+ UW solution. As indicated by creatine kinase-BB (CK-BB) release, reperfusion with CRS provided greater protection of endothelial cells after storage in high-K+ UW solution than after storage in high-Na+ UW solution. In study 2, livers were cold-preserved (24 h, 4 °C) in either high-K+ or high-Na+ UW solution, then flushed with either CRS or Wif solution at room temperature before reperfusion (120 min, 37 °C) with 5 % albumin-William's medium E. There was no statistical difference between the rinse solutions for bile flow and transaminases release. However, CRS improved bile indocyanine green excretion, which is known to be a marker of parenchymal and nonparenchymal cell integrity. Therefore, we can assume that this rinse solution protects rat liver grafts from reperfusion-induced microvascular damage. Received: 29 December 1997 Received after revision: 31 March 1998 Accepted: 15 April 1998  相似文献   

10.
A total of 81 rat kidney grafts, flushed out and cold stored in either Sacks' or University of Wisconsin (UW) solution, were transplantated into hemodiluted (Hct=30%±4%) or untreated (Hct=43%±3%) recipients. The cold ischemia times (CIT) used were 24 and 36 h. One week after transplantation, the surviving recipients (n=67) were contralaterally nephrectomized. The experiment was terminated after a total period of 4 weeks, and the percentage of surviving animals were determined for each treatment. Data was pooled and the results show that grafts cold stored in UW solution were viable to a significantly greater extent and after longer CIT than grafts cold stored in Sacks' solution (47% vs 23%;P<0.05). Recipient hemodilution did not improve graft viability (39% vs 32%; NS). Kidneys cold stored for 24 h were viable to a greater extent than kidneys with a CIT of 36 h (50% vs 15%;P<0.01).  相似文献   

11.
The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K + UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na + UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na + UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K + UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na + UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na + UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K + UW solution. Liver preservation in the high-Na + UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution. Received: 26 August 1997 Received after revision: 12 November 1997 Accepted: 28 November 1997  相似文献   

12.
The aim of this experimental study was to compare the preservation potency of University of Wisconsin (UW) and HTK (Bretschneider) solutions in an orthotopic liver transplantation (OLT) model in pigs. Livers were harvested using an in situ perfusion technique, where organs were flushed with the solution being tested, stored on ice — cold storage (CS) — for 2 or 24 h and then transplanted. Parameters monitored were liver enzymes in serum, hepatic water content, high energy phosphates, nuclear magnetic resonance (NMR) relaxation time T2, light microscopy and bile production. CS for 24 h is an extreme in pig liver preservation and is not compatible with animal survival. Biopsies showed drastic morphological changes and grafts did not produce bile in either group. (Bile production 2 h CS: HTK, 5.6 ± 1.8 ml/h; UW, 4.7 ± 2.3 ml/h) Enzyme release after reperfusion (ASGOT, ?LDH) was higher in long-term preservation. Hepatic tissue water content significantly decreased during CS in UW preserved livers. Edema alter reperfusion (?H20: HTK 24 h = + 5.6%, UW 24 h= + 4.8%) and regeneration capacity after reperfusion (UW 2 h = 63%, HTK 2 h = 55%, UW 24 h = 30%, HTK 24 h = 30%) were not significantly different. However, we did not observe major differences in preservation potency between the solutions tested. Differences were correlated, rather, with length 9 time of CS, than with the solution used. Therefore, HTK solution seemed to be a low potassium containing alternative to UW solution.  相似文献   

13.
It has been shown recently that inclusion of the calcium channel blocker nisoldipine to University of Wisconsin (UW) solution significantly improves survival after rat liver transplantation. To further elucidate the mechanisms involved, rat livers were stored for 1 h in UW solution with or without the addition of 1.4 gm nisoldipine (Miles, West Haven, Conn., USA). The liver grafts were investigated in vivo 90 min after transplantation by intravital fluorescence microscopy. Sinusoidal perfusion was reduced in all sublobular regions of the liver in the UW group (e. g. portal area: 76.7 ± 2.1%) and in the nisoldipine group (85.8 ± 1.5%). Diameters of liver sinusoids were comparably reduced in the UW and nisoldipine groups indicating that nisoldipine did not cause vasodilatation. Adhesion of leukocytes, however, rose significantly after liver transplantation particularly in periportal regions (25.8 ± 2.5%) compared to controls (17.1 ± 2.8%; P < 0.05). Adhesion of leukocytes was reduced when nisoldipine was included in UW solution (13.3 ± 1.7%; P < 0.05). Administration of latex particles, which were given in additional experimental groups, demonstrated an Impressive increase in phagocytic activity of Kupffer cells after liver transplantation in periportal and pericentral areas (161 ± 14% and 184 ± 19% of controls). Phagocytosis was significantly reduced by nisoldipine in the periportal region (101 ± 10%; P < 0.01). Thus, the beneficial effect of nisoldipine was most pronounced in periportal regions, where the majority of Kupffer cells are located and leukocyte adhesion was at a maximum.  相似文献   

14.
Background: Cold storage-induced injury to donor organs remains a persistent problem in transplantation medicine. We here evaluated a modified HTK solution including, among others, a new, membrane-permeable iron chelator, LK 614, in the isolated perfused rat liver model. Methods: Rat livers were stored at 4°C for 24 hr in modified HTK solution, in modified HTK solution with LK 614 or in traditional HTK solution, and reperfused for 60 min at 37°C with Krebs-Henseleit buffer (KH buffer). Bile secretion and lactate dehydrogenase (LDH) release into the perfusate were measured, and hepatic microcirculation evaluated optically after the addition of trypan blue to the perfusate. Biopsies were evaluated by a pathologist blinded to the experimental conditions. Results: Compared with HTK-preserved livers, LDH leakage was significantly lower and bile secretion significantly higher in the modified HTK solution with the iron chelator (both p <. 05), while values for the modified solution without the iron chelator were in between (no significant difference to either of the two other solutions). The hepatic microcirculation was also preserved best in livers stored in the modified HTK solution with LK 614. Histomorphological investigation confirmed the improved preservation in the modified HTK solution with LK 614. Conclusions: These results suggest that livers might be better preserved in modified HTK solution containing the iron chelator LK 614 (and also, but less so, in the modified solution without the iron chelator) than in the original HTK solution, and such a modified solution should now be evaluated in an animal model of liver transplantation.  相似文献   

15.
Guinea-pig livers are poorly reperfused when transplanted into rats. We have observed that, in contrast to that of the rat, the guinea-pig intrahepatic portal vein (PV) has a thick layer of smooth muscle. It is possible that, after perfusion of the liver with ice-cold saline, this could go into spasm, resulting in poor reperfusion. To test this hypothesis, guinea-pig livers were perfused with different solutions stored at varying temperatures and transplanted into LEW rats. To prevent xenograft hyperacute rejection, all xenograft recipients were treated with 80 U/kg cobra venom factor (CVF) i.v. on days –1 and 0. In addition to the percentage reperfusion, PV resistance and recipient survival were also monitored. In group I, liver xenografts perfused with ice-cold saline (4°C) reperfused poorly (20–30%), resulting in the development of portal hypertension (16.5 cmH2O vs. 12 cmH2O in naive LEW rats) and shortened mean survival time (11.7 ± 4.2 h). In contrast, group II livers perfused with saline at room temperature (23°C) underwent homogeneous reperfusion (98–100%) with no increase in portal vein resistance, indicating that low temperature was the main trigger for the spasm of the PV. Moreover, recipient survival in this group was significantly prolonged to a mean of 22 ± 2.6 h (P < 0.01). Although UW solution (group III) and the vasodilator sodium nitroprusside (NP) (group IV) when used alone improved the degree of hepatic reperfusion, it was still not optimal. The supplementation, however, of UW solution with NP in group V animals resulted in homogeneous reperfusion (98%) with no portal hypertension and consistent prolonged graft survival of 21.0 ± 1.7 h. Therefore, this study has determined that the riddle of the abnormal reperfusion of guinea-pig liver xenografts by rat blood is non-immune mediated and is due to the spasm of the strong smooth muscle in the PV tree produced by cold perfusates.  相似文献   

16.
To characterize the potential utility of the University of Wisconsin (UW) solution, 37 grafts preserved in UW solution (UW group) were compared with 38 grafts preserved in Euro-Collins (EC) solution (EC group). Patients in both groups underwent similar perioperative management. Donor and recipient data in the two groups were similar. The mean cold ischemia time (CIT) of the UW group was 6.51±2.06 h (range: 3.17–14.65 h); this was significantly longer than that of the EC group, of 4.80±1.68 h (range: 1.67–8.83h) (P<0.05). There were no significant differences in actuarial patient or graft survival between the two groups. Blood concentrations of aspartate aminotransferase (AST) within 12 h and lactic dehydogenase (LDH) within 6 h of reperfusion were significantly lower in the UW group than in the EC group, each being (P<0.05). The total bilirubin (TBR) concentration was lower in the UW group than in the EC group, but the difference was not significant. Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), and prothrombin time (PT) showed no significant differences between the two groups. There was no difference in the frequency of complications or rejection episodes between the two groups. However, gender identical grafts had a lower rejection than gender non-identical grafts in the UW group (P<0.05). Our data suggest that the UW solution reduces transplantation-related graft injury compared with the EC solution. Offprint requests to: T. Abe  相似文献   

17.
Effects of 5 cold storage solution on hepatic high energy phosphate metabolism and metabolic function were examined using the isolated perfused rat liver. University of Wisconsin (UW), Euro-Collins (EC), and 2 cardioplegic solutions, Bretschneider's HTK and St. Thomas Hospital solution, were studied for their protective capacity. Krebs-Henseleit bicarbonate buffer (KHB) was used to point out the effect of simple hypothermia. Liver ATP, total adenine nucleotides and energy charge losses were significantly lower during 21 h of storage in UW-preserved livers. Also, only UW-protected livers were able to complete regeneration of ATP and total adenine nucleotides after 1 h of reperfusion, whereas EC, HTK, St. Thomas and KHB stored livers only showed minimal regeneration. Concerning metabolic function, UW protected livers liberated significantly less LDH and sGOT as well in the 21-hour storage solution as into the perfusate under reperfusion conditions. This study demonstrates the capability of UW solution in liver preservation by its ability to maintain and restore high energy phosphates.  相似文献   

18.
In this study we have investigated the effects of hepatocytes glycogen storage on the quality of livers for transplantation. Rats were fed or fasted for 24 h and hepatocytes isolated and cold stored in UW solution for 24 and 48 hours. Viability of the cells was analyzed by LDH release after 2 hours incubation in L15 with O2. Also, rabbits were fed, fasted (48 h) or glucose fed (48 h) and livers cold stored for 6, 24 and 48 h in UW solution. Functions of the livers were analyzed by isolated perfusion for 2 hours. Hepatocytes from fasted rats released significantly more LDH than hepatocytes from fed rats after 24 and 48 h cold storage. In rabbit livers, fasting depleted glycogen by 85% but had no effect on ATP or glutathione concentration. Livers from fasted rabbits produced similar amount of bile, released similar concentrations of lactate dehydrogenase and aspartate transaminase into the perfusate, maintained similar concentrations of glutathione after 24 hours preservation when compared to fed animals. After 48 h preservation livers from fasted animals were less viable than livers from fed animals and the decrease of liver functions in livers from fasted animals preserved for 48 hours was prevented by feeding glucose. This study shows that liver glycogen storage in hepatocyte is an important metabolite for successful liver preservation. Glycogen may be a source for ATP and antioxydant synthesis during the early period of reperfusion.  相似文献   

19.
Background: Vascular endothelium plays a key role in regulation of vascular tone. Hyperkalemia has been demonstrated to impair the EDHF‐mediated endothelial function in coronary circulation. University of Wisconsin (UW) and Eruo‐collins (EC) solutions are used for organ preservation in transplantation surgery. The potassium concentration in UW or EC solutions is as high as 125 mmol/L or 115 mmol/L, respectively. This study was designed to examine whether hyperkalemia or storage with UW and EC solutions affects the relaxation mediated by EDHF in the porcine pulmonary micro‐arteries. Methods: Porcine pulmonary micro‐artery rings (diameter 200–450 μm) were studied in myograph (n = 8 in each group). After incubation with hyperkalemia (K+ 125 mmol/L, at 37° C), UW or EC solutions (at 4° C for 4 hours), EDHF‐mediated relaxation induced by bradykinin (BK, ?10 to ?6.5 log M) in the presence of inhibitors for cyclooxygenase (Indomethacin, 7 μM), nitric oxide synthase (NG‐nitro‐L‐arginine, 300 μM), and oxyhemoglobin (20 μM) was compared with control (Krebs' solution) in precontraction with U46619 (?7.5 log M). Results: The EDHF‐mediated relaxation to BK was 69.6 ± 6.3% compared with 97.1 ± 1.7% (p= 0.003) in control (no inhibitors). After incubation with hyperkalemia, the relaxation significantly decreased (38.6 ± 3.0% vs. 59.1 ± 7.4%, p= 0.03 ). Storage with UW or EC solutions also significantly decreased the relaxation (49.3 ± 7.3% vs. 65.2 ± 3.5%, p= 0.04 and 51.9 ± 8.4% vs. 60.3 ± 6.1%, p= 0.02 , respectively). Conclusions: In porcine pulmonary micro‐arteries, exposure to hyperkalemia or storage with UW or EC solutions at 4°C for 4 hours impairs the EDHF‐mediated endothelial function. The clinical significance of this effect should be further studied.  相似文献   

20.
The uptake of hyaluronic acid (HA) was used to assess preservation damage to sinusoidal endothelial cells (SEC) during cold storage and subsequent normothermic reperfusion of rat livers. After 8, 16, 24, and 48 h storage in University of Wisconsin (UW) solution, livers were gravity-flushed via the portal vein with a standard volume of cold UW solution containing 50 g/l HA. The effluent was collected for analysis of HA, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). The mean uptake of HA at 0 h was 59.1%±4.6% (mean±SEM). After 8 h of storage, HA uptake was similar (55.5%±7.3%), whereas after 16 h of storage it was reduced to 34.7%±5.8%. At 24 and 48 h of storage, no uptake of HA was found. In a second series of experiments, livers were stored in UW solution and subsequently reperfused for 90 min with a Krebs-Henseleit solution (37°C) in a recirculating system containing 150 g/l HA. Following 8 h of storage, 34.6%±8.0% of the initial HA concentration was taken up from the perfusate. After 16 and 24 h of storage, no uptake of HA was found. The results of this study indicate that damage to SEC occurs progressively during storage, leading to zero uptake of HA by the rat livers at 24 h of cold ischemia time. Additional reperfusion injury to the SEC was demonstrated by the reduced ability of the SEC to take up HA following normothermic reperfusion. The uptake of exogenous HA in preserved livers, used as a tool to assess SEC injury, enables the detection of early preservation damage.  相似文献   

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