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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver regeneration plays a key role in restoring the liver/body ratio after partial liver transplantation. However, hepatic ischemia hinders the proliferative response of the hepatocytes. In this study, different ways of improving the regenerating capacity of ischemic hepatocytes are tested. Following 70% hepatectomy and 15 min of normothermic liver ischemia, the percentage of regenerating hepatocytes and the regenerative gradient are assessed. Cyclosporine A (hepatotrophic agent), superoxide dismutase and folinic acid (antioxidants), administered during the ischemic period, have significantly increased these indices. The later drug has restored the regenerative response to the levels of normoperfused livers.
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PMID:Effect of allopurinol, folinic acid, SOD and cyclosporine A on ischemic liver regeneration. 778 46

Since an occlusion of the vascular inflow to the liver is a useful technique in liver surgery, a relation between ischemia and regeneration in the liver is particularly important. The purpose of this study was to evaluate the effect of ischemic duration on liver regeneration after massive hepatectomy. Animals were subjected to segmental liver ischemia. After 30, 60, or 90 min, nonischemic liver lobes were resected (70% hepatectomy). Hepatectomy without prior liver ischemia was performed in the control group. On the 1st, 3rd, 5th, and 7th days following hepatectomy, a BrdU labeling index was calculated as a marker of liver regeneration. AST, ALT, and liver adeninenucleotides were also measured. Although 30 min of liver ischemia resulted in higher peak AST and ALT levels, liver regeneration and ATP levels were significantly higher than those in control animals. Ninety minutes of liver ischemia resulted in significantly lower liver regeneration and ATP levels compared with the other treatment paradigms. Liver regeneration and ATP levels were almost identical to those in control animals, in rats with 60 min of ischemia preceding hepatectomy. We conclude that livers regenerative capacities can tolerate significant ischemia and that relatively brief periods of ischemia can even accelerate liver regeneration.
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PMID:Duration of liver ischemia and hepatic regeneration after hepatectomy in rats. 788 25

Ischemia is a common situation, not always desirable, in liver surgery. In any case, it implies cellular damage that would be worth avoiding. In the present study, different antioxidant drugs (superoxide-dismutase, allopurinol and folinic acid) are administered prior to liver reperfusion in order to reduce ischemic damage. Liver regeneration, following a 70% hepatectomy and 15 minutes of normothermic hepatic ischemia, serves as an indirect functional test of the reperfused liver. SOD (6 mg/kg) and allopurinol (50 mg/kg) have accelerated hepatocytic DNA synthesis without increasing the number or percentage of activated hepatocytes. However, the folinic acid has proved to be very effective, counteracting the deleterious effect of liver ischemia on hepatocytic regeneration.
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PMID:[Effect of antioxidative therapy on regeneration of ischemic liver]. 833 7

Liver regeneration is an important process that allows for recovery from hepatic injuries caused by viruses, toxins, ischemia, surgery, and transplantation. Previously, we identified > 70 immediate-early genes induced in regenerating liver after hepatectomy, 41 of which were novel. While it is expected that the proteins encoded by these genes may have important roles in regulating progression through the G1 phase of the cell cycle during regeneration, we were surprised to note that many of these "early" genes are expressed for extended periods during the hepatic growth response. Here we define several patterns of expression of immediate-early, delayed-early, and liver-specific genes during the 9-d period after hepatectomy. One pattern of induction parallels the major growth period of the liver that ends at 60-72 h after hepatectomy. A second pattern has two peaks coincident with the first and second G1 phases of the two hepatic cell cycles. A third group, which includes liver-specific genes such as C/EBP alpha, shows maximal expression after the growth period. Although the peak in DNA synthesis in nonparenchymal cells occur 24 h later than in hepatocytes, most of the genes studied demonstrate similar induction in both cell types. This finding suggests that the G0/G1 transition occurs simultaneously in all cells in the liver, but that the G1 phase of nonparenchymal cells may be relatively prolonged. Finally, we examined the expression of > 70 genes in clinical settings that could induce liver regeneration, including after perfusion in a donor liver, hepatic ischemia, and fulminant hepatic failure. We found that a small number of early and liver-specific genes were selectively activated in human livers under these conditions, and we thereby provide a potential means of measuring the caliber of the regenerative response in clinical situations.
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PMID:Induction patterns of 70 genes during nine days after hepatectomy define the temporal course of liver regeneration. 847 85

Liver regeneration has been described after heterotopic liver transplantation, small-for-size orthotopic liver transplantation and reduced-size liver transplantation. In this report, we document the regenerative response of a whole liver transplant to major resection for the first time. A right hepatic lobectomy for liver ischemia was performed in a 30-year-old female after transplantation for autoimmune disease of the liver. Volumetric analysis of computed tomography (CT) scans revealed a preoperative liver volume of 1,961 mL, whereas analysis of the 6-week posthepatectomy CT scan showed a volume of 1,820 mL. Factors influencing regeneration in the setting of a liver transplant include rejection, ischemia/thrombosis, infection, or cyclosporine hepatotrophic/hepatotoxic effects. These factors, balanced with the intrinsic ability of hepatocytes to achieve a standard liver volume, determine the extent of regeneration.
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PMID:Regeneration of a transplanted liver after right hepatic lobectomy. 934 53

Liver regeneration in a patient with fulminant hepatic failure (FHF) who underwent living-related partial liver transplantation (LRLT) was investigated regarding hepatic growth factors. The patient was a 16-yr-old Japanese male who developed severe subacute FHF. LRLT was performed using an extended left lobe of the ABO matched patient's mother. In the recipient, the pre-transplant levels of both plasma hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta were extremely high and rapidly decreased following the liver replacement. The liver volume evaluated using a CAT scan increased 195% after 2 wk in graft liver and 110% after 2 wk in the hepatectomized donor. The explanted liver (FHF liver), the liver from donor (normal liver), and the graft liver [the 3rd post-transplant day (POD 3)] were all investigated immunohistochemically. FHF liver: No liver regeneration was observed [proliferative cell nuclear antigen (PCNA) labeling index (L.I.): 0%]. In the liver, both HGF in the hepatocytes and c-met on the membrane of the hepatocytes were positive. TGF-beta was positive in the hepatocytes and no apoptosis was detected by the TUNEL method. Donor liver (POD 0): Few PCNA stained hepatocytes were detected. No HGF was detected but c-met was clearly detected on the cell membrane of the hepatocytes. Neither TGF-beta nor apoptosis was detected. Graft liver (POD 3): The PCNA L.I. was conspicuous at 40%. HGF was positive in non-parenchymal cells and c-met was positive in the cytoplasm of the hepatocytes. TGF-beta was negative while apoptosis was positive in the zone 3 hepatocytes. In conclusion, these findings suggested that the liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF-beta. On POD 3, the transplanted graft was in a vigorous regenerative status in comparison to that in the hepatectomized donor. The HGF/c-met system is thought to be involved in the mechanism of regeneration. Intrahepatic apoptosis was detected in the graft on the 3rd post-transplant day probably due to transient ischemia in the liver, which was not related to the Fas/Fas-ligand system.
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PMID:Changes in liver regenerative factors in a case of living-related liver transplantation. 1061 46

Exposure to toxic metals and pollutants is a major environmental problem. Cadmium is a metal causing acute hepatic injury but the mechanism of this phenomenon is poorly understood. In the present study, we investigated the mechanism and time-course of cadmium-induced liver injury in rats, with emphasis being placed on apoptosis in parenchymal and nonparenchymal liver cells. Cadmium (3.5 mg/kg body weight) was injected intraperitoneally and the rats were killed 0, 9, 12, 16, 24, 48 and 60 h later. The extent of liver injury was evaluated for necrosis, apoptosis, peliosis, mitoses and inflammatory infiltration in hematoxylin-eosin-stained liver sections, and by assaying serum enzyme activities. The number of cells that died via apoptosis was quantified by TUNEL assay. The identification of nonparenchymal liver cells and activated Kupffer cells was performed histochemically. Liver regeneration was evaluated by assaying the activity of liver thymidine kinase and by the rate of 3H-thymidine incorporation into DNA. Both cadmium-induced necrotic cell death and parenchymal cell apoptosis showed a biphasic elevation at 12 and 48 h and peaked at 48 and 12 h, respectively. Nonparenchymal cell apoptosis peaked at 48 h. Peliosis hepatis, another characteristic form of liver injury, was first observed at 16 h and, at all time points, closely correlated with the apoptotic index of nonparenchymal liver cells, where the lesion was also maximial at 48 h. Kupffer cell activation and neutrophil infiltration were minimal for all time points examined. Based on thymidine kinase activity, liver regeneration was found to discern a classic biphasic peak pattern at 12 and 48 h. It was very interesting to observe that cadmium-induced liver injury did not involve inflammation at any time point. Apoptosis seems to be a major mechanism for the removal of damaged cells, and constitutes the major type of cell death in nonparenchymal liver cells. Apoptosis of nonparenchymal cells is the basis of the pathogenesis of peliosis hepatis. The first peaks of necrosis and parenchymal cell apoptosis seem to evolve as a result of direct cadmium effects whereas the latter ones result from ischemia.
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PMID:Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis. 1368 93

Transient increased intra-abdominal pressure (IIAP) due to carbon dioxide insufflation is suspected to cause a form of ischemia-reperfusion injury. Considering this, a study was designed to assess the effect of transient IIAP on liver regeneration in a rat model. Six groups of animals (each n = 6) were studied. While experiments in Group 1 (IIAP+PHR) were subjected to IIAP, following partial hepatic resection (PHR), those in Group 2 (IIAP) experiments were subjected to IIAP. Animals in Group 3 (IR+PHR) were subjected to liver ischemia-reperfusion (IR) following PHR, and those in Group 4 (IR) underwent only IR. Group 5 (PHR) and Group 6 (healthy) served as controls. Blood was taken for assessment of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 with enzyme-linked immunosorbent assay (ELISA) at day 5 postoperatively. Each rat was then given a lethal injection of pentobarbital. Gravimetric analysis and immunohistochemistry staining for proliferating cell nuclear antigen (PCNA) were used for assessments of liver regeneration. Apoptosis was assessed by immunohistochemical TUNEL index, expressed as the number of positive cells/per total number of cells at the same time. Although mean liver regeneration rates of Group 1 and Group 3 were the same, that of Group 5 was the highest (p = .04). Serum TNF-alpha levels of Group 1 versus Group 3 were 340 pg/ml versus 352 pg/ml. Serum IL-l levels of Group 1 versus Group 3 were 124 pg/ml versus 135 pg/ml. Serum TNl-alpha and IL-6 levels of Group 1 and Group 3 were the same at the first day of surgical procedure (p > .05). Mean serum TNF-alpha levels of Group 5 (387 pg/ml) were significantly higher than those of both Group 1 and Group 3 at 24 h of operation. Serum IL-6 levels of Group 5 (174 pg/ml) at the same time was higher than those of Group 1 and Group 3 at the same time (p = .01). Proliferating cell nuclear antigen indices of Group 1, Group 2, Group 3, Group 4, and Group 6 were the same; however, the mean PCNA-labeling index of Group 5 was higher than those of the others. There were no significant differences between the groups (p > .05). Liver regeneration is suppressed by transient IIAP. However, the effect of IIAP on liver apoptosis needs to be clarified.
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PMID:The impact of transient elevation of intra-abdominal pressure on liver regeneration in the rat. 1576 98

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.
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PMID:Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration. 1621 53

Brief periods of tissue ischemia produced tissue resistance to prolonged ischemia and reperfusion, a phenomenon called ischemic preconditioning. The mechanisms of ischemic preconditioning were examined in a rat warm ischemia-reperfusion model as well as the effect of ischemic preconditioning on liver regeneration. Ischemic preconditioning decreased liver injury after warm ischemia-reperfusion, which was reversed by Kupffer cell depletion. Ischemic preconditioning stimulated Kupffer cells to produce reactive oxygen species. Scavengers of reactive oxygen species reversed the effect of ischemic preconditioning, and pretreatment with sublethal dose of hydrogen peroxide mimicked ischemic preconditioning effect. Rat livers were preconditioned by ischemia and subjected to 70% partial hepatectomy. Liver regeneration was then evaluated serially. Ischemic preconditioning promoted liver regeneration, which was reversed by adenosine A2 receptor antagonism and mimicked by adenosine A2 receptor agonism. Promotion of liver regeneration by ischemic preconditioning and adenosine A2 receptor agonism were reversed by Kupffer cell depletion. In conclusion, ischemic preconditioning stimulates Kupffer cells to produce reactive oxygen species, leading to hepatocyte protection against warm ischemia-reperfusion injury; and ischemic preconditioning promoted liver regeneration via adenosine A2 receptor pathway in Kupffer cells.
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PMID:Ischemic preconditioning in liver pathophysiology. 1756 70


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