Hepatic blood inflow occlusion without hemihepatic artery control in treatment of hepatocellular carcinoma

AIM:To investigate the clinical significance of hepatic blood inflow occlusion without hemihepatic artery control (BIOwHAC) in the treatment of hepatocellular carcinoma (HCC).METHODS:Fifty-nine patients with HCC were divided into 3 groups based on the technique used for achieving hepatic vascular occlusion:group 1,vascular occlusion was achieved by the Pringle maneuver (n=20);group 2,by hemihepatic vascular occlusion (HVO) (n=20);and group 3,by BIOwHAC (n=19).We compared the procedures among the three groups in term of operation time,intraoperative bleeding,postoperative liver function,postoperative complications,and length of hospital stay.RESULTS:There were no statistically significant differences (P > 0.05) in age,sex,pathological diagnosis,preoperative Child’s disease grade,hepatic function,and tumor size among the three groups.No intraoperative complications or deaths occurrred,and there were no significant intergroup differences (P > 0.05) in intraoperative bleeding,hepatic function change 3 and 7 d after operation,the incidence of complications,and length of hospital stay.BIOwHAC and Pringle maneuver required a significantly shorter operation time than HVO;the difference in the serum alanine aminotransferase or aspartate aminotransferase levels before and 1 d after operation was more significant in the BIOwHAC and HVO groups than in the Pringle maneuver group (P < 0.05).CONCLUSION:BIOwHAC is convenient and safe;this technique causes slight hepatic ischemia-reperfusion injury similar to HVO.     

Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna

Background and Aim: We investigated the role of the prophylactic administration of the antioxidant 2‐mercaptoethane sulfonate (mesna) on the hepatocyte‐regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver. Methods: Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor‐κB (NF‐κB) activity were assessed. Results: Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF‐κB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF‐κB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle‐induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF‐κB, while attenuating liver injury after PH under Pringle. Conclusion: The excessive activation of NF‐κB is related to the suppression of hepatocyte‐regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle‐induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF‐κB activation.     

Splenic artery ligation improves remnant liver function in partially hepatectomized rats with ischemia/reperfusion injury

Background: In liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes severe ischemia/reperfusion injury in the remnant liver. Our aim was to investigate the effects of splenic artery ligation on the liver function in partially hepatectomized rat with the Pringle maneuver. Methods: The Pringle maneuver was conducted for 30 min just before a two‐thirds partial hepatectomy. Splenic artery ligation was performed before the Pringle maneuver. The efficacy of splenic artery ligation was assessed by survival, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), recovery of remnant liver weight, and portal pressure. Results: On day 3, animal survival was four rats of 12 in partially hepatectomized rats with the Pringle maneuver and 10 rats of 12 in the splenic artery ligation‐treated partially hepatectomized rats with the Pringle maneuver. A two‐thirds partial hepatectomy alone or splenic artery ligation itself did not show any effects on the survival. Compared with partially hepatectomized rats with the Pringle maneuver, splenic artery‐ligated animals had lower serum AST and ALT levels, and higher recovery of remnant liver weight. Splenic artery ligation significantly reduced the portal pressure and also decreased the fatality in excessively hepatectomized rats. Conclusions: Splenic artery ligation ameliorated the remnant liver function in partially hepatectomized rats with the Pringle maneuver and excessively hepatectomized rats. The amelioration may be mediated at least by decreasing portal pressure.     

Protective effect of prostaglandin E1 against ischemia/reperfusion-induced liver injury: results of a prospective, randomized study in cirrhotic patients undergoing subsegmentectomy

Background/Aims: The cytoprotective effects of prostaglandin E1 on livers suffering from ischemia/reperfusion injury in the clinical setting are unproved. These effects were examined, focusing on inflammatory cytokine and nitric oxide metabolism.Methods: Twenty-four cirrhotic patients with hepatocellular carcinoma undergoing subsegmentectomy under ischemia induced only by Pringle's maneuver were divided into two groups (patients given prostaglandin E1 by injection and untreated controls) and postoperative results were compared. Peripheral blood was taken perioperatively and the plasma aminotransferase, cytokines and nitrate/nitrite levels of the two groups were compared. Two liver specimens were taken from each patient, one before ischemia and the other after hepatectomy, and the levels of inducible nitric oxide synthase and cytokine mRNAs and proteins were analyzed.Results: Although no apparent differences were recognized in postoperative complications or duration of postoperative hospital stay between the groups, the perioperative plasma aminotransferase level was significantly lower in the prostaglandin E1 group. Significant differences were also seen in interleukin-6 and nitrate plasma levels during the observation period and the interleukin-6 protein levels in the liver supernatants after hepatectomy in the two groups. In contrast, no significant differences were apparent between the interleukin-1 beta and tumor necrosis factor-alpha plasma levels of the two groups. The corrected fluorescence activities of interleukin-6 and inducible nitric oxide synthase mRNAs in the liver after hepatectomy correlated significantly. No interleukin-1 beta or tumor necrosis factor-alpha mRNAs or proteins were detected.Conclusions: Prostaglandin E1 exerted hepatoprotective effects on livers suffering from ischemia/reperfusion injury, and interleukin-6 might play an important role in these effects.     

Effects of prostaglandin E1 administration during hepatectomy for cirrhotic hepatocellular carcinoma

BACKGROUND/AIMS: Prostaglandin E1 has been used in hepatectomy based on a few limited clinical studies suggesting that PGE1 improves liver function. The aim of this study was to evaluate the effects of PGE1 administration during hepatectomy for cirrhotic hepatocellular carcinoma. METHODOLOGY: Forty-three patients undergoing hepatectomy for cirrhotic hepatocellular carcinoma were divided into 2 groups: hepatectomy with Prostaglandin E1 treatment (PG group; n = 19) and without Prostaglandin E1 treatment (control group; n = 24). Prostaglandin E1 (0.02-0.07 microgram/kg/min) was administered intravenously from beginning to end of surgery in the PG group. RESULTS: There were no significant differences between groups with respect to age, gender, preoperative liver and renal function, or intraoperative variables such as blood loss, weight of resected liver and total clamping time by the Pringle maneuver. No patient had severe postoperative complications. Initial postoperative maximum concentrations of serum total bilirubin, creatinine, and blood urea nitrogen in the PG group were significantly lower than those in the control group. CONCLUSIONS: Prostaglandin E1 administration during hepatectomy for cirrhotic heptocellular carcinoma resulted in improved renal and hepatic function.     

Impact of selective prostaglandin E1 treatment on graft perfusion and function after liver transplantation

BACKGROUND/AIMS: In several clinical trials, the prophylactic application of prostaglandin E1 did not demonstrate a significant effect on incidence of primary graft nonfunction after liver transplantation. The aim of this study was to evaluate the effect of a selective prostaglandin E1 treatment in liver transplant patients with initially compromised perfusion and thereby depressed early posttransplant graft function. METHODOLOGY: A total of 142 patients were enrolled in this study. In all of them, duplexsonography was performed daily to generally assess patency of allograft vessels and to specifically calculate the resistive index of the hepatic artery. Intravenous therapy with a prostaglandin E1 analogue (Alprostadil, 0.5 microg/kg/h) was initiated in 67 patients after determination of a primarily elevated (>0.75) and posttransplant increasing resistive index of the hepatic artery that was associated with continuously elevating aminotransferases. RESULTS: After initiation of treatment, the arterial resistive index decreased significantly from 0.83+/-0.1 to 0.72+/-0.1 on the first day of application (P<0.05). Primarily elevated serum levels of aspartate aminotransferase (AST: Alprostadil: 890+/-180 IU/L: Control: 375+/-98 IU/L) and alanine aminotransferase (ALT: Alprostadil: 850+/-178 IU/L, Control: 310+/-79 IU/L) decreased significantly and reached values comparable to the control group after three days of therapy (AST: Alprostadil: 190+/-40 IU/L, Control: 150+/-45 IU/L ALT: Alprostadil: 280+/-57 IU/L, Control: 180+/-50 IU/L) (P<0.05). Only 2 grafts with initial compromised perfusion and function (3%) developed primary graft nonfunction. CONCLUSIONS: Prostaglandin E1 seems to be effective in ameliorating ischemia-reperfusion injury to the liver in patients with elevated arterial vascular resistance and early depressed graft function after liver transplantation. Duplexsonography in combination with graft function are useful tools for indicating and monitoring treatment.     

Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats

BACKGROUND AND AIMS: Reactive oxygen species have been implicated in the development of hepatic ischemia/reperfusion (I/R) injury. I/R injury remains an important problem in massive hepatectomy and organ transplantation. The aim of this study was to examine the effect of edaravone, a newly synthesized free radical scavenger, on I/R injury in the remnant liver after partial hepatectomy in rats. METHODS: Partial (70%) hepatic ischemia was induced in rats by occluding the hepatic artery, portal vein, and bile duct to left and median lobes of liver. Total hepatic ischemia (Pringle maneuver) was induced by occluding the hepatoduodenal ligament. Edaravone was intravenously administered to rats just before reperfusion and partial (70%) hepatectomy was performed just after reperfusion. RESULTS: Edaravone significantly reduced the increases in the levels of serum alanine aminotransferase and aspartate aminotransferase in rats with liver injury induced by 90-min of partial ischemia followed by 120-min of reperfusion. Histopathological analysis showed that edaravone prevented inflammatory changes in the livers with I/R injury. Edaravone also decreased the levels of myeloperoxidase activity, which is an index of neutrophil infiltration, and interleukin-6 mRNA, which is a proinflammatory cytokine. Additionally, edaravone improved the survival rate in partial hepatectomy rats with I/R injury induced by the Pringle maneuver. CONCLUSIONS: Edaravone administration prior to reperfusion protected the liver against I/R injury. Edaravone also improved the function of the remnant liver with I/R injury after partial hepatectomy. Therefore, edaravone may have applicability for major hepatectomy and liver transplantation in the clinical setting.     

Splenic artery ligation: A protection against hepatic ischemia/reperfusion injury in partially hepatectomized rats

Aim: In liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes ischemia/reperfusion (I/R) injury in the remnant liver. Heme oxygenase (HO)‐1 has a cytoprotective role against this injury. Our aim is to investigate whether splenic artery ligation induces HO‐1 expression in the liver and ameliorates the hepatic I/R injury in partially hepatectomized rats. Methods: Rats underwent splenic artery ligation by occluding the main splenic artery. Two days later, the total hepatic ischemia (Pringle maneuver) was conducted, and then a two‐thirds partial hepatectomy (PH) was performed just before the start of reperfusion. HO inhibitor was twice injected s.c. at 3 and 16 h before the Pringle maneuver. HO‐1 levels were determined by western blotting. Liver injury was biochemically assessed. Results: In normal rats, HO‐1 was highly expressed in the spleen, but not in the liver. Splenic artery ligation induced HO‐1 in the livers. When rats underwent 20 and 30 min of Pringle maneuver/PH, survival rates were 28% and 8%, respectively. Splenic artery ligation significantly improved both the survival rates: 73% and 56%, respectively. Under these conditions, administration of HO‐1 inhibitor at least partly negated the efficacy of splenic artery ligation. Splenic artery ligation also increased the recovery rate of the remnant liver mass and platelet counts in Pringle maneuver/PH‐treated rats. Conclusion: Splenic artery ligation was significantly effective on the hepatic I/R injury in partially hepatectomized rats. Induction of HO‐1 may be at least partly involved in the improvement of this injury.     

Effects of prior splenectomy on remnant liver after partial hepatectomy with Pringle maneuver in rats.

BACKGROUND/AIMS: In the case of the liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes hepatic ischemia/reperfusion (I/R) injury that strongly affects the recovery of patients. The present study investigated the effects of prior splenectomy on the remnant liver in partial hepatectomized rat with Pringle maneuver. METHODS: Pringle maneuver was conducted just before a two-thirds partial hepatectomy. Efficacy of splenectomy was assessed by survival rate, serum alanine aminotransferase (ALT), neutrophil infiltration into liver, recovery of remnant liver weight, and liver proliferating cell nuclear antigen (PCNA) levels. Ischemic preconditioning was performed as follows; 10 min of total hepatic ischemia followed by 10 min of reperfusion. RESULTS: In partial hepatectomized rats with 30 min of Pringle maneuver, seven out of 12 rats died within 3 days. On the other hand, when splenectomy was performed on 3 days before the maneuver, only one out of 12 rats died. When prior splenectomy was performed on eight and 18 days before the Pringle maneuver, respectively, similar efficacy was observed. In addition, prior splenectomy on 3 days before the maneuver showed that serum ALT activity, neutrophil infiltration, recovery of remnant liver weight, and PCNA levels in partial hepatectomized rats with Pringle maneuver were also ameliorated as compared with those of control rats without splenectomy. When effects of prior splenectomy were compared with those of ischemic preconditioning in these situations, efficacy of prior splenectomy was comparable with that of the ischemic preconditioning. CONCLUSIONS: Prior splenectomy ameliorated the I/R injury in the remnant liver after partial hepatectomy with Pringle maneuver. Effects of prior splenectomy may influence the liver for long duration, because splenectomy on 18 days before the maneuver still exerts effective action.     

Postoperative day one serum alanine amino-transferase does not predict patient morbidity and mortality after elective liver resection in non-cirrhotic patients

Serum aminotransferases have been used as sur-rogate markers for liver ischemia-reperfusion injury that fol-lows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase (ALT) correlate with patient outcome after liver resection. We assessed whether postopera-tive day 1 (POD 1) ALT could be used to predict patient mor-bidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our in-stitution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient’s morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver signiifcantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because of the low number of mortalities. Patients undergoing concur-rent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not cor-relate with patient morbidity after elective liver resection.     

Cytokine response to human liver ischemia-reperfusion injury during hepatectomy: marker of injury or surgical stress?

BACKGROUND/AIMS: The aim of this study was to evaluate the inflammatory or antiinflammatory cytokine response to ischemia-reperfusion during hepatectomy and to find a useful marker of injury or surgical stress during hepatic ischemia-reperfusion. METHODOLOGY: In 9 patients with liver disease who underwent hepatectomy using the Pringle maneuver, serum cytokines, including alanine transaminase, aspartate transaminase, and hyaluronic acid, were measured just prior to vascular occlusion; 5, 10 and 15 min after initial clamping; and 3 min after initial declamping. RESULTS: The mean concentrations of aspartate transaminase and alanine transaminase did not significantly differ before and after ischemia-reperfusion during hepatectomy. However, mean concentrations of hyaluronic acid after ischemia-reperfusion were significantly (P < 0.03) higher than before clamping. Although there were no significant differences in the mean concentrations of IL-1 beta, IL-6, IL-8, IL-10 and TNF-alpha among, before and after ischemia-reperfusion, the mean concentrations of granulocyte colony-stimulating factor after ischemia-reperfusion and macrophage colony-stimulating factor after reperfusion were significantly (P < 0.05) higher than before clamping. CONCLUSIONS: Although hepatic parenchymal cell function was maintained after ischemia-reperfusion during hepatectomy, sinusoidal endothelial cell dysfunction was found. Release of granulocyte colony-stimulating factor and macrophage colony-stimulating factor after ischemia-reperfusion were also found. These cytokines and hyaluronic acid may be useful indicators in the early phase of human ischemia-reperfusion injury during hepatectomy.     

Prostaglandin E(1) protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T cells in mice

Prostaglandin E series (PGEs) are known to protect against lipopolysaccharide (LPS)-induced liver injury by down-regulating the production of inflammatory cytokines. We show here a novel mechanism whereby prostaglandin E(1) protects mice against liver injury after Escherichia coli infection. Prostaglandin E(1) administration suppressed circulating interleukin 12 (IL-12) levels but increased the IL-10 production after E. coli challenge. Furthermore, prostaglandin E(1)-alpha-cyclodextrin (PGE(1)) shifted the Th1/Th2 balance of CD3(intermediate) IL-2Rbeta(+) T cells in the liver to a dominant Th2-like response. Neutralization of endogenous IL-4 by administration of anti-IL-4 monoclonal antibody (mAb) diminished the inhibitory effect of prostaglandin E(1) on liver injury after E. coli challenge. These results suggested that the Th2-like response of liver T cells may be at least partly involved in the mechanism whereby prostaglandin E(1) protects against E. coli-induced liver injury.     

Suprahepatic vena cava manipulative bleeding alleviates hepatic ischemia–reperfusion injury in rats

BACKGROUND: Little is known about time course and peak level of reactive oxygen species in suprahepatic vena cava after liver ischemia-reperfusion. OBJECTIVE: To determine time course and peak level of reactive oxygen species in suprahepatic vena cava after liver ischemia-reperfusion. To focus on the effects of suprahepatic vena cava manipulative bleeding on the hepatic ischemia-reperfusion injury in rat model. METHODS: In experiment Part I, blood was taken from suprahepatic vena cava and infrahepatic vena cava for malondialdehyde detection at different time points after reperfusion. Furthermore, we treated the experimental rats in Part II by suprahepatic vena cava manipulative bleeding or infrahepatic vena cava manipulative bleeding at 10 min after reperfusion. RESULTS: In experiment Part I, malondialdehyde concentration in suprahepatic vena cava elevated obviously with time and peaked at 10 min after reperfusion. The numbers of accumulated polymorphonuclear neutrophils was significantly increased in ischemia-reperfusion group from 10 min after reperfusion, compared with sham-operated group. In Part II, 2% of body weight suprahepatic vena cava manipulative bleeding with blood transfusion at 10 min after reperfusion significantly decreased circulating malondialdehyde, tumour necrosis factor-alpha, endothelin-1, hyaluronic acid, alanine aminotransferase, aspartate aminotransferase levels and polymorphonuclear neutrophil infiltrations in the liver. The 7-day survival rate of this group was 68.75% (11/16) which was significantly higher than other groups. CONCLUSIONS: We provided the first evidence that 2% of body weight suprahepatic vena cava manipulative bleeding with blood transfusion at 10 min after reperfusion significantly prevented liver ischemia-reperfusion injury.     

The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia-reperfusion injury of the rat

BACKGROUND/AIMS: This study was designed to investigate the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the rat liver. METHODOLOGY: Male Sprague-Dawley rats were used in this experimental study. Total hepatic ischemia was induced with a clamping portal triad. The animals were divided into two groups: the control group and the FK group, in which FK3311 (FK, 1.0 mg/kg) was administered via the penile vein. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured 2 h after reperfusion, while those of thromboxane (Tx) B2 and 6-ketoprostaglandin (PG) F1alpha (stable metabolites of TxA2 and PGI2) were measured 30 min after reperfusion. The liver tissue blood flow was measured at preischemia, end-ischemia, and 30, 60, 90, and 120 min after reperfusion. The liver tissues obtained from animals at 2h after reperfusion were excised for histopathology. RESULTS: The serum levels of AST, ALT, and LDH were significantly lower in the FK group than in the control group. Similarly, in the FK group, the serum levels of TxB2 were significantly lower than in the control group. By contrast, the 6-keto-PG F1a levels were not significantly reduced. The liver tissue blood flow at 120 min after reperfusion was significantly higher in the FK group than in the control group. The histopathological study showed that hepatic tissue damage was milder in the FK group than in the control group. CONCLUSIONS: FK has protective effects on hepatic ischemia-reperfusion injury stemming from the marked inhibition of TxA2.     

The effect of intraportal administration of prostaglandin E1 on liver blood flow and liver function

BACKGROUND/AIMS: Prostaglandin E1 (PGE1) exerts a hepatic cytoprotective action directly and indirectly through enhancing hepatic blood flow. Although PGE1 is usually administered systemically, more than 60% of PGE1 is inactivated during only a single passage through the lung. By administering PGE1 intraportally the intrahepatic level of this drug can be increased effectively and liver dysfunction might be prevented. In this study, the effect of intraportal administration of PGE1 to patients who underwent hepatectomy was estimated. METHODOLOGY: Twenty patients who underwent hepatectomy from January 1995 to December 1996 were divided into 2 groups, i.e., a PGE1 group (n=8) and a control group (n=12). Laboratory data and hepatic portal blood flow were examined before and after hepatectomy. In the PGE 1 group, PGE 1 was continuously infused at a dose of 120 microg/day for 5 days through a catheter inserted into the portal vein via the gastroepiploic vein. RESULTS: There was no difference in the post-operative change in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) between the 2 groups. Elevation of total bilirubin was more significantly suppressed in the PG group than in the control group. Total branched-chain amino acids and the tyrosine ratio reached their peak on the 5th post-operative day (POD) and were significantly higher in the PG group. Post-operative portal blood flow was significantly increased in the PG group. CONCLUSIONS: Our results indicated that continuous intraportal administration of small doses of PGE1 is effective for the protection of hepatic function after hepatectomy.     

Effect on gastric and duodenal mucosal prostaglandins of repeated intake of therapeutic doses of naproxen and etodolac in rheumatoid arthritis.

The synthesis of gastric and duodenal mucosal prostaglandin E2, prostaglandin I2, and thromboxane B2 during a 60 minute incubation of biopsy specimens, the degree of endoscopic and histological damage, and the anti-inflammatory response were all studied after a four week, double blind study of therapeutic doses of two non-steroidal anti-inflammatory drugs, naproxen and etodolac, received by 27 patients with active rheumatoid arthritis (13 receiving naproxen, 14 etodolac). Prostaglandin values after treatment did not differ from the baseline levels when all the patients were analysed as one group. Subgroup analysis showed that naproxen suppressed gastric prostaglandin E2 from a median of 29 to 9 ng/mg protein, duodenal prostaglandin E2 from 34 to 11 ng/mg, and duodenal prostaglandin I2 from 62 to 15 ng/mg protein. No overall suppression occurred with etodolac. Also, on the second assessment patients receiving naproxen had lower gastric and duodenal prostaglandin E2 and prostaglandin I2, but higher values of duodenal thromboxane B2, than patients receiving etodolac. Both drugs had comparable anti-arthritic activity and caused microscopic gastritis in similar proportions of patients. No correlation was detected between prostaglandin values and the mucosal damage which developed in seven patients receiving naproxen (54%) and three receiving etodolac (21%). These findings indicate that, unlike naproxen, etodolac does not seem to affect gastric or duodenal prostaglandin synthesis; other mechanisms of injury need to be considered.     

Erythropoietin ameliorates early ischemia-reperfusion injury following the Pringle maneuver

AIM:To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM),in comparison with conventional steroid administration in a prospective randomized trial. METHODS:Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups:(1) A steroid group (STRD, n= 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2)...     

Intestinal ischemia-reperfusion impairs liver regeneration after partial hepatectomy in rats

BACKGROUND/AIMS: The deleterious effects of intestinal ischemia-reperfusion on liver are realized, but its effect on the regenerative capacity of the liver has not been studied. Our aim in this study was to determine the effect of intestinal ischemia-reperfusion on liver regeneration. METHODOLOGY: Sprague-Dawley rats were randomly divided into six groups; two sham-operated, two hepatectomy, and two hepatectomy with intestinal ischemia-reperfusion groups. To create intestinal ischemia-reperfusion, the superior mesenteric artery and collateral arteries supplying the small intestine were occluded for 20 minutes. Partial hepatectomy was performed during the period of ischemia. Ischemia-reperfusion injury in the mucosal layer of the small intestine was scored in light microscopy. Liver regeneration parameters (proliferating cell nuclear antigen labeling index for hepatocytes and liver regeneration rate), and serum levels of aspartate aminotransferase and alanine aminotransferase were studied on day 1 or 4 after operation. RESULTS: Mucosal injury score was high in the hepatectomy with intestinal ischemia-reperfusion groups. Liver regeneration rate and proliferating cell nuclear antigen labeling index were less in these groups than the hepatectomy groups on day 1 and 4. There were no differences in the serum levels of aspartate aminotransferase and alanine aminotransferase between hepatectomy and hepatectomy with intestinal ischemia-reperfusion groups. The mortality rate was higher in the hepatectomy with intestinal ischemia-reperfusion groups than the other groups. CONCLUSIONS: Ischemia and reperfusion of the small intestine impaired liver regeneration with high mortality after partial hepatectomy in the rats.     

Hepatic resection under the Pringle maneuver induces endotoxemia and lipoperoxidative attack in the jaundiced rat liver

Sixty percent hepatectomy under two times of the Pringle maneuver (temporal occlusion of the hepatic inflow of the hepatic artery and portal vein) for 25 min was carried out on rats with obstructive jaundice. Hepatic energy charge which was markedly decreased during the Pringle maneuver did not recover 3 hrs after release of the maneuver. In addition, systemic endotoxemia associated with increased level of malondialdehyde and decreased levels of total glutathione and alpha-tocopherol in the liver was demonstrated. These changes were more dominant in rats with obstructive jaundice for 3 weeks than those for 1 week. It can be said that deteriorated hepatic energy charge after release of the Pringle maneuver may partly be caused by the production of oxygen free radicals which may be enhanced by endotoxemia in resection of the jaundiced liver. In contrast, after release of the Pringle maneuver, deterioration of hepatic energy charge due to oxidative attack was not found in jaundiced rats without hepatic resection.     

The comparison of electron microscopy and scintigraphy in determining the protective effect of dimethylsulphoxide (DMSO) on ischemia/reperfusion injury through Pringle maneuver.

BACKGROUND/AIMS: We investigated the role of the electron microscopy and hepatobiliary scintigraphy in determining the effect of DMSO (dimethysulphoxide) and ischemia/reperfusion injury in the liver after the Pringle maneuver. METHODOLOGY: Twenty-four rabbits were divided into the following groups; A: Control group, B: Pringle, C: 10 mg/kg DMSO, D: 1 g/kg DMSO + Pringle. Group A was considered as a control group and only laparotomy was applied. Group B was exposed to Pringle maneuver only. Group C was given 10 mg/kg of DMSO via the vena cava inferior. Group D was given 1 g/kg of DMSO. A clamp was fastened for the groups of B, C and D in the 30th minute of the Pringle maneuver and a biopsy was applied five minutes later. Fifteen minutes later a dynamic hepatobiliary scintigraphy was applied. From dynamic images, liver peak time and activity half time of the liver were obtained. RESULTS: It was found that liver peak time and liver activity half time values of the group B, C and D were significantly longer than group A. Liver peak time and liver activity half time values of group B was not different from group C. However, some values of group D were found to be significantly shorter than groups B and C. In the electron microscopy examination, only in group B were some specific degenerative changes observed in the sinusoids. We observed less irreversible changes in group C than in group B. On the other hand, the least irreversible changes were in group D. CONCLUSIONS: As a conclusion, while electron microscopy is regarded as the "gold standard", hepatobiliary scintigraphy may be thought of as an easily applicable method in determining the ischemic reperfusion injury in the clinical comparison of the protective agents.