Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.     

Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold-preserved warm-reperfused rat livers

BACKGROUND/AIM: A mechanism suggested to cause injury to preserved organs is the generation of oxygen free radicals. Lipid peroxidation is one of the biological damages caused by oxygen free radicals. It is our aim to investigate whether magnolol, a strong antioxidant, suppresses the generation of oxygen free radicals and improves the viability of cold-preserved warm-reperfused rat livers. MATERIALS AND METHODS: In vitro lipid peroxidation was induced in rat hepatic mitochondria with ADP and FeSO4. The inhibitory effect of magnolol on lipid peroxidation was measured with oxygen consumption and malondialdehyde (MDA) formation. Subsequently, we preserved and reperfused rat livers in preservation solutions that contained magnolol. The hepatic enzymes and liver MDA were measured to assess the protective effect of magnolol on isolated rat livers. RESULTS: In rat hepatic mitochondria, magnolol was 470 times more potent than alpha-tocopherol in inhibiting oxygen consumption and 340 times more potent than alpha-tocopherol in inhibiting MDA formation. Addition of magnolol to Ringer's lactate solution had a protective effect, in terms of MDA formation and leakage of hepatic enzymes, on warm-reperfused but not cold-stored liver tissue. Addition of magnolol to University of Wisconsin (UW) solution, a widely used preservation solution, did not modify the effect of this solution on isolated liver tissues. CONCLUSIONS: We conclude that magnolol is an effective antioxidant and suppresses lipid peroxidation in rat liver mitochondria and can be used as a rinsing solution in protecting transplanted organs from lipid peroxidation during reperfusion, especially for those organs not preserved with UW solution.     

Intraoperative hemodynamic investigations during portacaval shunt

We studied the hemodynamics of hepatic blood flow before and after creation of portacaval shunts in 28 patients. Electromagnetic flow recordings were used to measure hepatic arterial flow (HAF) and portal venous flow (PVF) with respect to total hepatic blood flow (THBF). No correlation between PVF and portal pressure was found, but PVF was directly related to liver function. The concept that patients with low PVF tolerate shunts better (with respect to postoperative course and encephalopathy) than those with high PVF was not supported. Our investigations suggest the existence of a compensatory mechanism that tends to maintain THBF by increasing HAF following creation of a shunt. This compensatory increase occurs only in those patients with good liver function and normal or enlarged livers.     

Prospective Evaluation of Intraoperative Hemodynamics in Liver Transplantation with Whole,Partial and DCD Grafts

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.     

The function of a colloid in liver cold-storage preservation

The value of colloid in preservation of the liver by cold storage has not yet been fully clarified. Therefore, we studied the effects of colloid on cell swelling, liver weight, and bile production after cold storage in rat liver tissue slices and isolated rabbit liver. In rat liver tissue slices cold-stored for 24 hr in UW solution, total tissue water (TTW) was the same as in the control freshly unpreserved tissue and omitting the colloid (hydroxyethyl starch) from the UW solution did not affect the TTW. However, after cold storage for 24 hr in Perfadex, TTW was markedly increased (by 100%, P less than 0.001). Omitting the colloid in this solution, dextran, or replacing it with hydroxyethyl starch, did not affect this increase in TTW. Thus, the hypothermia-induced cell swelling evident after preservation in Perfadex was not prevented by colloid. Rabbit liver cold-stored in UW solution for 24 hr lost 15.4 +/- 4.7% of weight, but omitting the colloid from UW solution decreased this weight loss to 3.1 +/- 3% (P less than 0.01). In contrast, rabbit livers cold-preserved in colloid-free Perfadex gained 23.3 +/- 5.7% in weight. Adding colloid, either dextran or hydroxyethyl starch, decreased significantly this weight gain, to 9 +/- 3.7% and 10.4 +/- 1.8%, respectively (P less than 0.01), probably as a result of colloid osmotic pressure, preventing the interstitial edema. Rabbit livers preserved for 24 hr in UW solution, with or without colloid, produced the same amount of bile as control unpreserved livers. In contrast, livers preserved in colloid-free Perfadex for 24 hr had a markedly impaired bile production (3.9 +/- 0.9 ml/100 g) as compared with control livers (15.5 +/- 2.6 ml/100 g, P less than 0.01). Colloid partially restored this impaired bile production, to 8 +/- 1.4 mg/100 g by dextran and to 8.5 +/- 1.7 ml/100 g by hydroxyethyl starch, respectively (P less than 0.01). Thus, although colloids do not prevent the hypothermia-induced cell swelling, they prevent the development of interstitial edema, and, hence, improve the liver function.     

Improved microcirculation by low‐viscosity histidine– tryptophan–ketoglutarate graft flush and subsequent cold storage in University of Wisconsin solution: results of an orthotopic rat liver transplantation model

As previously shown in a model of isolated rat liver perfusion, the combined use of an initial graft flush with low‐viscosity histidine–tryptophan–ketoglutarate (HTK) solution followed by cold storage in University of Wisconsin (UW) solution markedly improved the preservation during an extended cold storage period. In this study, we aimed to transfer our results into an in vivo model of orthotopic rat liver transplantation, and to elucidate the potential mechanism of the improved preservation by focusing on the hepatic microcirculation. Livers were harvested from male Wistar rats. Aortic perfusion with a pressure of 100 cm H₂O was performed with either UW (group UW) or HTK (groups UW and HTK_UW), followed by additional back‐table perfusion with UW (group HTK_UW). After 20‐h cold storage at 4 °C, livers were orthotopically transplanted with reconstructing the hepatic artery. As measured by bile flow and liver enzymes, HTK flush followed by UW storage was superior compared to single use of either UW or HTK solution. The hepatic microcirculation was significantly improved, as shown by the increased percentage of reperfused sinusoids and reduced sinusoidal leucostasis. HTK and UW effectively reduce ischaemia‐reperfusion injury after liver transplantation. By combining the comparative advantages of both solutions, a cumulative effect resulting in an improved preservation was shown. Thus, this mechanism improves microcirculatory reperfusion.     

肝缺血再灌注后肝内血流动力学的变化

目的探讨肝脏缺血再灌注（I／R）后肝内分流（IHSF）和功能性肝血流（FHBF）的变化。方法健康雄性SD大鼠l2只，作右侧颈动脉、颈静脉插管；开腹后，经回结肠静脉作门静脉插管，分别用以输血、输液、给药、留样、检测等。大鼠经部分肝I／R制模后，随机分为2组（每组6只）：（1）正常对照组（对照组），术中只分离肝周围韧带，不作肝门阻断及再灌注。（2）缺血再灌注组（1／R组，实验组），进行45min的肝门阻断及60min的再灌注。然后两组均经门静脉输注D一山梨醇（10mmol／L，0．2mL／min），2min后同时取颈动脉、门静脉、肝静脉血各1mL。测定门静脉血流量（PVF）、肝动脉血流量（HAF）。计算肝脏山梨醇摄取率、FHBF和IHSF。结果两组PVF，HAF及总肝血流量（THBF）无明显统计学差异；与对照组比较，I／R组肝脏山梨醇摄取率和FHBF减少，IHSF增加（P〈0．01）。结论肝I／R后，肝内血流动力学变化表现为肝内门一体分流开放，功能性肝血流减少。     

Delivery of the bioactive gas hydrogen sulfide during cold preservation of rat liver: effects on hepatic function in an ex vivo model

The insults sustained by transplanted livers (hepatectomy, hypothermic preservation, and normothermic reperfusion) could compromise hepatic function. Hydrogen sulfide (H₂S) is a physiologic gaseous signaling molecule, like nitric oxide (NO) and carbon monoxide (CO). We examined the effect of diallyl disulfide as a H₂S donor during hypothermic preservation and reperfusion on intrahepatic resistance (IVR), lactate dehydrogenase (LDH) release, bile production, oxygen consumption, bromosulfophthalein (BSP) depuration and histology in an isolated perfused rat liver model (IPRL), after 48 h of hypothermic storage (4°C) in University of Wisconsin solution (UW, Viaspan). Livers were retrieved from male Wistar rats. Three experimental groups were analyzed: Control group (CON): IPRL was performed after surgery; UW: IPRL was performed in livers preserved (48 h—4°C) in UW; and UWS: IPRL was performed in livers preserved (48 h—4°C) in UW in the presence of 3.4 mM diallyl disulfide. Hypothermic preservation injuries were manifested at reperfusion by a slight increment in IHR and LDH release compared with the control group. Also, bile production for the control group (1.32 µL/min/g of liver) seemed to be diminished after preservation by 73% in UW and 69% in UW H₂S group at the end of normothermic reperfusion. Liver samples analyzed by hematoxylin/eosin clearly showed the deleterious effect of cold storage process, partially reversed (dilated sinusoids and vacuolization attenuation) by the addition of a H₂S delivery compound to the preservation solution. Hepatic clearance (HC) of BSP was affected by cold storage of livers, but there were no noticeable differences between livers preserved with or without diallyl disulfide. Meanwhile, livers preserved in the presence of H₂S donor showed an enhanced capacity for BSP uptake (k_ACON = 0.29 min^?1; k_AUW = 0.29 min^?1; k_AUWS = 0.36 min^?1). In summary, our animal model suggests that hepatic hypothermic preservation for transplantation affects liver function and hepatic depuration of BSP, and implies that the inclusion of an H₂S donor during hypothermic preservation could improve standard methods of preparing livers for transplant.     

Experimental evaluation of the effects of the intraportal administration of cyclic guanosine monophosphate on ischemia/reperfusion in the porcine liver

This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3′,5′ monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n=6). Saline water was administered in the same way in the control group (n=6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function of after warm ischemia of porcine liver.     

Effects of exogenous endothelin-1 application on liver perfusion in native and transplanted porcine livers

PURPOSE: This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-1 (ET) plasma concentrations on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). METHODS: A standardized gradual increment in systemic ET plasma concentration (0-58 pg/ml) was induced by continuous ET-1 infusion into the portal vein in both groups (A: n = 10, B: n = 10). Control animals received only saline (n = 5, each group). Hepatic microcirculation (HMC) was quantified by thermodiffusion electrodes, hepatic artery flow (HAF), and portal venous flow (PVF) by Doppler flowmetry. RESULTS: No changes in ET or perfusion parameters were observed in controls. The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A from 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 +/- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Baseline HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml/100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/- 32 ml/100 g/min. No significant alteration in systemic circulation was noted at the ET concentrations investigated. CONCLUSIONS: Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominantly by reduction of portal venous flow, while the effect of ET on HAF was less pronounced. Characteristics of flow impairment in transplanted and native livers were analogous after short cold ischemic graft storage (6 h).     

Donation After Cardiac Death: Dynamic Graft Reconditioning During or After Ischemic Preservation?

The benefit of gaseous oxygenation during storage of liver grafts from donors after cardiac death should be investigated as applied either during the whole period of preservation or only for the last 2 h prior to reperfusion. Rat livers were explanted 30 min after cardiac arrest of the donor and cold-stored (CS) for 20 h. Some grafts were subjected to venous systemic oxygen persufflation (VSOP) either for 20 h or for only 2 h subsequent to 18 h of CS. Viability of the livers was assessed thereafter by warm reperfusion in vitro. Twenty hours VSOP and 18 h CS + 2 h VSOP prevented mitochondrial protein breakdown of mitochondrial heat shock protein 70 and promoted a significant and approximately twofold increase in hepatic oxygen consumption, bile production, and energetic recovery upon warm reperfusion. No differences were seen whether VSOP was performed for 20 h or for only 2 h prior to reperfusion. Both techniques significantly abrogated parenchymal enzyme loss (alanine aminotransferase, aspartate aminotransferase) upon reperfusion compared with simple 20 h CS. An increase in perfusate levels of the mitochondrial enzyme glutamate dehydrogenase was observed only in the 20 h VSOP group. In conclusion, viability of donation after cardiac death liver grafts can still be augmented, similarly to continuous aerobic storage, by only endischemic reconditioning, both protocols preventing initial mitochondrial dysfunction and subsequent tissue injury.     

Effect of S-nitrosoglutathione (GSNO) added to the University of Wisconsin solution (UW): I) Morphological alteration during cold preservation/reperfusion of rat liver

Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and stroma. In this study we demonstrated the benefit of adding S-nitrosoglutathione (GSNO) to the UW solution before cold storage, as an effective Nitric Oxide (NO) donor to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (4 degrees C-48Hs) and then reperfused 60 minutes in the isolated perfused rat liver model (IPRL). Normal untreated livers and perfused livers, but not preserved were used as controls. Parenchymal damages were evaluated with Hematoxylin-Eosin stain and an inmunohistochemistry assay for albumin was used as functional test. To study the stroma, collagen type III and I networks were analyzed using Picro-sirius Red stain and Gordon Sweets' method for reticulin. After 48 Hs of cold preservation in UW solution livers showed few rounded endothelial cells inside sinusoidal lumen and extended areas of cell vacuolation. Albumin distribution was evident only around central veins and middle zones of the hepatic lobule. Collagens III and I networks were disorganized. When preserved with the addition of 100 microM GSNO and then reperfused, the hepatic morphology, in general, was conserved showing little vacuolation, fewer endothelial cells inside sinusoids and good albumin distribution around central veins and middle zones. The stroma had organized networks of collagen III and I. We concluded that the addition of 100 microM GSNO as a NO donor, can improve UW solution properties to preserve rat liver by maintaining the hepatic morphology and avoiding hepatic injury post cold preservation/reperfusion.     

High-Na + low-K + UW cold storage solution reduces reperfusion injuries of the rat liver graft

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     

Direct measurement of hepatic blood flow during living donor liver transplantation in children

Background

The changes in liver blood flow associated with living donor liver transplantation (LDLT) in children have not yet been studied. The aim of the present study was to investigate changes in hepatic hemodynamics before and after pediatric partial liver transplantation.

Methods

In 7 pediatric recipients with congenital cholestasis and native liver Child-Pugh classes B and C, portal vein flow (PVF) and hepatic arterial flow (HAF) were measured using an ultrasonic transit time flow meter before removal of the native liver and after transplantation and compared with donor left PVF and donor left HAF.

Results

The mean portal contribution to total hepatic blood flow was markedly decreased in the recipient native liver compared with that in the donor (69% ± 15% vs 32% ± 15%; P = .0003) and after reperfusion changed to almost the same ratio as that in the donor liver (73% ± 18%; P < .0001).

Conclusion

The extreme imbalance between PVF and HAF that is common in implanted partial liver in adult LDLT recipients was not observed in pediatric LDLT. After transplantation of an appropriately sized liver graft, the portal contribution to total liver blood flow normalized to the value for normal liver.     

Comparative evaluation of Celsior solution versus Viaspan in a pig liver transplantation model.

BACKGROUND: In a pig liver transplantation model, we compared the effects of Celsior solution (CS), an extracellular preservation solution, with Viaspan (University of Wisconsin solution, UW) on graft function and animal survival. METHODS: Pig livers were flushed with either CS or UW solution and cold-stored for 12 hr (group 1) or for 8 to 10 hr (group 2). Grafts were transplanted orthotopically. Intrahepatic reduced and oxidized glutathione and adenine nucleotides were evaluated 1 hr after reperfusion. Liver function of transplanted animals was monitored for up to 6 days by serum transaminases, total bilirubin, purine nucleoside phosphorylase, and prothrombin levels. RESULTS: In group 1, all animals died within 24 hr after reperfusion regardless of the preservation solution used. In group 2, no significant difference was seen in survival between the CS (72%) and the UW (67%) groups 6 days after transplantation, and there were no statistically significant differences in the biochemical data. There were no differences in histological evaluation of the livers at the time of death or killing of the animals between the CS and UW groups. CONCLUSION: Within the limits of this pilot study, CS is equivalent to UW in terms of graft function and animal survival.     

Advantages of normothermic perfusion over cold storage in liver preservation

BACKGROUND: To minimize the ischemia-reperfusion injury that occurs to the liver with the current method of preservation and transplantation, we have used an extracorporeal circuit to preserve the liver with normothermic, oxygenated, sanguineous perfusion. In this study, we directly compared preservation by the standard method of simple cold storage in University of Wisconsin (UW) solution with preservation by perfusion. METHODS: Porcine livers were harvested from large white sows weighing between 30 and 50 kg by the standard procedure for human retrieval. The livers were preserved for 24 hr by either cold storage in UW solution (n=5) or by perfusion with oxygenated autologous blood at body temperature (n=5). The extracorporeal circuit used included a centrifugal pump, heat exchanger, and oxygenator. Both groups were then tested on the circuit for a 24 hr reperfusion phase, analyzing synthetic function, metabolic capacity, hemodynamics, markers of hepatocyte and reperfusion injury, and histology. RESULTS: Livers preserved with normothermic perfusion were significantly superior (P=0.05) to cold-stored livers in terms of bile production, factor V production, glucose metabolism, and galactose clearance. Cold-stored livers showed significantly higher levels of hepatocellular enzymes in the perfusate and were found to have significantly more damage by a blinded histological scoring system. CONCLUSIONS: Normothermic sanguineous oxygenated perfusion is a superior method of preservation compared with simple cold storage in UW solution. In addition, perfusion allows the possibility to assess viability of the graft before transplantation.     

Intraoperative flow measurement of native liver and allograft during orthotopic liver transplantation in children

Hepatic hemodynamic changes during liver transplantation (OLT) in children have not yet been studied. We measured intraoperative portal vein flow (PVF) and hepatic arterial flow (HAF) (mL/min) in 53 children and 58 grafts during OLT. Flows were measured in the native organ and in the allograft. In the native liver, PVF and HAF are similar; after transplantation they return to the physiological situation. No flow differences were seen between whole and partial grafts. Among the 8 (14%) portal vein thromboses, PVF was lower in both the native liver and the graft than in the no thrombosis group (P < .05). PVF <5 mL/min/kg was a risk factor to develop PV thrombosis. No graft loss occurred in 3 cases without PVF at the time of OLTs despite the observation that repermeabilization was not possible. In 4 patients with PVF <5 mL/min/kg, after tying a spontaneous spleno-renal shunt (n = 3) or performing a porto-renal vein anastomosis (n = 1), PVF reached >20 mL/min/kg, avoiding thrombosis. In conclusion, PVF and HAF measurements during pediatric OLT may predict patients at high risk for development of PV thrombosis.     

Successful 72-hour cold storage of dog kidneys with UW solution

Effects of three cold-storage solutions on kidney function in dogs were examined with the isolated perfused (IPK) kidney model and the autotransplant model. EuroCollins' (EC) solution, phosphate-buffered sucrose solution, and a new solution developed at the University of Wisconsin (UW) were studied. Kidneys were cold-stored for 48 hr or 72 hr. With the IPK model, cold storage for 48 hr or 72 hr in each of the three solutions caused creatinine clearance to decrease by 80%-90%. More protein was excreted by kidneys stored for 48 hr in PBS solution than by kidneys stored in EC or UW solution; protein excretion after 72 hr of storage was similar for kidneys stored in EC or UW solution. Sodium reabsorption decreased after 48 hr or 72 hr of storage, but was higher in kidneys stored in UW solution (83% and 56%, respectively) than in EC solution (52% and 22%, respectively). With the autotransplant model, 40% of the kidneys were viable after 48-hr storage in PBS solution, but 80% viable when stored in EC solution and 100% were viable when stored in UW solution. All kidneys were viable when stored for 72 hr in UW solution; none were viable when stored for 72 hr in EC solution. These results suggest that UW solution effectively preserves kidneys for 72 hr. We previously reported successful 72-hr pancreas preservation. Recently UW solution was able to preserve canine livers for 30 hr. Thus, this single solution appears to be effective for preserving all intraabdominal organs and may simplify cold storage of organs for transplantation.     

Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E₁ (PGE₁) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE₁ at 0.2 g/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE₁ was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE₁ is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.     

Effect of cold aerobic perfusion on nonparenchymal cell viability of rat livers

Abstract We investigated the effect of oxygen supply on hepatic cellular viability during cold perfusion storage of rat livers- A perfluoro- N -methyldecahydroisoquinoline (FMIQ) emulsion is used as an oxygen carrier. The composition of the perfusate containing 20 w/v% FMIQ is essentially the same as the University of Wisconsin (UW) solution except for the exclusion of hydroxyethyl starch. Rat livers were perfused at 4°C for up to 24 h with either UW solution (group I, oxygenated; group II, unoxygenated) or FMIQ solution (group III, oxygenated; group IV, unoxygenated). After perfusion storage, the livers were reperfused with warm (37 °C) oxygenated or cold (4 °C) unoxygenated Krebs-Henseleit bicarbonate buffer, and nuclear trypan blue uptake was measured as the index of cell death. With warm oxygenated reperfusion, there remained less than 2% noviable parenchymal cells up to 24 h, regardless of perfusate or oxygenation. In UW-perfused livers, the proportion of nonviable nonprenchymal cells (NPC) increased progressively regardless of oxygenation, the values in groups I and II in the periportal field at 24 h being 39.9 ± 4.7% (mean ± SD) and 36.5 ± 4.2%, respectively. By contrast, in FMIQ-perfused livers, dye uptake by NPC was significantly reduced with oxygenation (16.9 ± 5.7% and 39.4%± 9.1% at 24 h in groups III and IV; P < 0.001). With cold unoxygenated reperfusion, livers in groups I, II, and IV showed a significant decrease of nonviable NPC, while those in group III showed no significant changes. These data indicate that oxygen supply during perfusion storage of the liver may ameliorate lethal injury to NPC precipitated during reperfusion.