Plasminogen activator in bile during extracorporeal perfusion of pig liver

Plasminogen activator activity was studied in bile and perfusate during extracorporeal pig liver perfusion. Plasminogen activator activity in bile was up to 58 times greater than in perfusate. A high level of plasminogen activator activity in bile was also found after the addition of urokinase to the perfusate. These results suggest that bile is the main route of active excretion of plasminogen activator and urokinase from the liver in experimental liver perfusion.     

Effect of aging process on liver function in extracorporeal rat liver perfusion

BACKGROUND/AIMS: Liver function appears to be well maintained in old age. However, the current state of knowledge about liver aging processes is incomplete. In this study, using extracorporeal liver perfusion model, we evaluated the differences between liver function in young and old rats. METHODOLOGY: Livers were harvested from groups of young (2 months) and old (12 months) rats and perfused for 2 hours with a perfusion fluid. After 10, 30, 60, 90 and 120 minutes of perfusion, glucose concentration as well as enzyme levels (alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase) were measured. On completion of perfusion all bile produced was collected. RESULTS: All measured parameters changed significantly as a function of perfusion time in both groups. Changes in enzyme levels were most evident between 90 and 120 minutes of perfusion. In contrast to old rats, where glucose concentration decreased during all time periods of perfusion, in young rats the glucose concentration increased at the beginning of perfusion. CONCLUSIONS: The results suggest that livers obtained from older rats are damaged to a greater extent and are more susceptible to unfavorable conditions during perfusion than livers obtained from younger rats. Also, single measurement of liver enzymes is not enough for complete liver function assessment.     

体外肝脏灌注技术研究现状及展望

急性肝衰竭病死率高,肝移植是唯一有效的治疗方法,但由于肝源短缺,迫切需要有效的等待肝源或肝自我再生期间的"桥接治疗"技术。体外肝脏灌注技术作为生物人工肝的一种类型,被寄望于能够暂时替代体内衰竭的肝脏,延长患者生命,从20世纪50年代至今不断有学者对其进行研究改进,随着新材料、新技术以及基因编辑工程的发展,近年来呈现新的研究热潮。该文对体外肝脏灌注的研究历史、现状以及面临的问题进行综述,并对未来发展方向进行进一步展望。     

Preservation of non-heart-beating donor livers in extracorporeal liver perfusion and histidine-trytophan-ketoglutarate solution

AIM： To compare the preservation of non-heart- beating donor （NHBD） livers in cold histidine-trytophan- ketoglutarate （HTK） solution and extracorporeal liver perfusion （ECLP）. METHODS： Livers harvested from health pigs were stored for 10 h in cold HTK solution （group A, n = 4） or perfused with oxygenated autologous blood at body temperature （group B, n = 4）. Both groups were then tested on the circuit for 4 h. Bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of extracorporeal livers were tested in each group. Liver tissues from each group were examined at the end of reperfusion. RESULTS： At 1, 2, 3 and 4 h after reperfusion, bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of livers in group A were statistically different from those in group B （P 〈 0.05 or P 〈 0.01）. CONCLUSION： ECLP is better than HTK solution to preserve NHBD livers. ECLP can assess the graft viabilitybefore liver transplantation.     

Aspects of our liver support systems using extracorporeal xenoperfusion of pig or baboon liver: review

Artificial liver support systems using xenoperfusion of pig or baboon liver have metabolic activity and there is the possibility that they could substitute for total liver functions; however, several problems have yet to be solved. In our early clinical experience, a method of cross-hemodialysis with interposed cuprophane membrane was employed in order to avoid immunological reactions in patients. Sixteen patients with hepatic failure were treated by this method. Although the coma grade was ameliorated in 65% of the patients, the ultimate survival rate was 18.9%. In this clinical trial, the indication for liver support was clarified based on hepatic mitochondrial functions. This unsatisfactory result could also be attributed to insufficient effects of the device, due to the interposed membrane, and also to damage of the supporting livers due to hyperacute xenoperfusion injury. Recent investigations in the field of xenotransplantations have shown us possibilities for controlling xenogeneic hyperacute rejection. Suppression of complement activation enabled long-term xenoperfusion of supporting livers with high metabolic activity. The administration of prostaglandin E1 or soluble complement receptor type 1, and the use of transgenic pig livers expressing human decay-accelerating factor, may be promising methods to estab-lish highly active artificial liver support systems using xenoperfusion.     

Clinical significance of accelerated fibrinolysis in liver disease

We compared site and severity of bleeding in 46 patients with cirrhosis of the liver and accelerated fibrinolysis (defined as a dilute whole-blood clot lysis time less than 2 h) to 44 patients with cirrhosis of the liver and normal fibrinolysis (dilute whole-blood clot lysis time greater than 4 h). Patients with accelerated fibrinolysis had a significantly higher incidence of severe soft-tissue bleeding after trauma and a trend toward increased intracranial bleeding. Mucosal, postoperative, and gastrointestinal bleeding were equally frequent in the two groups. The median partial thromboplastin time was significantly longer, and the median bilirubin and fibrin/fibrinogen degradation product levels were significantly higher in the group with accelerated fibrinolysis, but median prothrombin time, platelet count, and levels of fibrinogen and serum albumin were comparable. The fibrinolytic inhibitor epsilon-aminocaproic acid successfully controlled bleeding in 4 of 6 cases used. Accelerated fibrinolysis may predispose patients with cirrhosis to soft-tissue and intracranial bleeding.     

Concentrations of catecholamines in transplanted hearts after extracorporeal perfusion and cold storage

Summary Using different perfusion regimes and orthograde implantation, some investigators have found sufficient heart function after extracorporeal perfusion of hearts for 24 and even 72h. However, we found no significant improvement of perfused hearts compared to cold stored hearts after a 9-h extracorporeal period. A possible explanation for this finding could be the excessive liberation of catecholamines during ischemia, as has been demonstrated in isolated perfused hearts. Therefore, the aim of this study was to investigate whether concentrations of noradrenaline and dihydroxyphenylglycol (DOPEG) — a noradrenaline metabolite — increased pathologically during continuous extracorporeal heart perfusion for 5 h in pigs, in comparison to hearts stored at 4°C. The venoarterial differences in noradrenaline and DOPEG were not significantly different in the two groups. Concentrations of lactate and pyruvate decreased substantially after 3-h hypothermic perfusion. The lactate/pyruvate ratio remained at a value of 25–35. Only after the end of the extracorporeal circulation did this ratio reach a value of 40–65. In our model, these findings demonstrate that the excessive liberation of catecholamines is not a reason for heart failure after cold storage or perfusion.All animals were cared for in a licensed animal facility according to NIH guidelines (Guide for the Care and Use of Laboratory Animals, NIH Publication No. 85-23, revised 1985). The experimental protocol was reviewed and approved by the Government of Unterfranken, Germany, Ref. No. 211-2531.01-41/91