Hepatic Pedicle Occlusion Research Articles

Application of Intraoperative Ultrasound in Laparoscopic Liver Resection with Pringle Maneuver: A Comparative Study with the Pringle Maneuver.

Background: Appropriate surgical techniques for controlling bleeding and preserving residual liver function are key to the success of laparoscopic liver resection. This study aims to evaluate the application effect of intraoperative ultrasound in the Pringle maneuver of laparoscopic liver resection. Materials and Methods: Between January 2022 and June 2023, 100 patients underwent laparoscopic liver resection and were randomly allocated to receive application of intraoperative ultrasound for Pringle maneuver (intraoperative ultrasound group, n = 50) or conventional Pringle maneuver (conventional group, n = 50). Intraoperative blood loss, blood transfusion, operation time, hepatic portal block time, complications (bile leakage, hemorrhage, ascites, and posthepatectomy liver failure), and hospital stay were compared between groups, along with the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels at postoperative days 1, 3, and 7. Results: The operation time, postoperative ALT, AST, and TB levels on postoperative days 1, 3, and 7, complications (bile leakage, hemorrhage, ascites, and posthepatectomy liver failures), and hospital stay were comparable between groups. Compared with the conventional group, the intraoperative ultrasound group had significantly less intraoperative blood loss (P = .015), lower blood transfusion rate (P = .035), and less hepatic portal block time (P = .012). Conclusions: Applying intraoperative ultrasound in laparoscopic liver resection for hepatic pedicle occlusion is a safe, simple, and effective method.

Liver resection for octogenarians in a French center: prolonged hepatic pedicle occlusion and male sex increase major complications.

The prolonged life expectancy and increase in aging of the population have led surgeons to propose hepatectomy in the elderly population. In this study, we evaluate the surgical outcome of octogenarians in a single French center. Between 2000 and 2020, 78 patients over 80 years old were retrospectively analyzed. The risk factors of major complications (Clavien-Dindo ≥ grade IIIa) and patient performance after surgery by using textbook outcome (TO) (no surgical complications, no prolonged hospital stay (≤ 15 days), no readmission ≤90 days after discharge, and no mortality ≤90 days after surgery) were studied. The main surgical indication was for malignancy (96%), including mainly colorectal liver metastases (n = 41; 53%) and hepatocellular carcinoma (n = 22; 28%), and major hepatectomy was performed in 28 patients (36%). There were 6 (8%) postoperative mortalities. The most frequent complications were pulmonary (n = 22; 32%), followed by renal insufficiency (n = 22; 28%) and delirium (n = 16; 21%). Major complications occurred in 19 (24%)patients. On multivariate analysis,the main risk factors for major complicationswere the median vascular clamping time (0 vs 35; P = 0.04) and male sex (P = 0.046). TO was ultimately achieved in 30 patients (38%), and there was no prognostic factor for achievement of TO. Hepatectomy in octogenarians is associated with acceptable morbidity and mortality. Meanwhile, prolonged hepatic pedicle clamping should be avoided especially if hepatectomy is planned in a male patient.

Patient blood management for liver resection: consensus statements using Delphi methodology

BackgroundBlood loss and transfusion remain a significant concern in liver resection (LR). Patient blood management (PBM) programs reduce use of transfusions and improve outcomes and costs, but are not standardized for LR. This study sought to create an expert consensus statement on PBM for LR using modified Delphi methodology. MethodsAn expert panel representing hepato-biliary surgery, anesthesiology, and transfusion medicine was invited to participate. 28 statements addressing the 3 pillars of PBM were created. Panelists were asked to rate statements on a 7-point Likert scale. Three-rounds of iterative rating and feedback were completed anonymously, followed by an in-person meeting. Consensus was reached with at least 70% agreement. ResultsThe 35 experts panel recommended routine pre-operative transfusion risk assessment, and investigation and management of anemia with iron supplementation. Intra-operatively, restrictive fluid administration without routine central line insertion was recommended, along with intermittent hepatic pedicle occlusion and surgical techniques considerations. Specific criteria for restrictive intra-operative and post-operative transfusion strategy were recommended. ConclusionsPBM for LR included medical and technical interventions throughout the perioperative continuum, addressing specificities of LR. Diffusion and adoption of these recommendations can standardize PBM for LR to improve patient outcomes and resource utilization.

Hepatic Pedicle Occlusion with the Pringle Maneuver During Difficult Laparoscopic Cholecystectomy Reduces the Conversion Rate.

In the presence of cholecystitis or portal hypertension, hemorrhage is common during laparoscopic cholecystectomy (LC) because the vessels of Calot's triangle are fragile and tortuous. Bleeding can obstruct surgical field visibility and increase conversion rates and risk of common bile duct injury. The Pringle maneuver is a simple occlusion approach that could limit blood flow from the hepatic pedicle, thus controlling bleeding to provide a clear surgical field to reduce conversion rate. In this study, we aimed to investigate the feasibility, effectiveness and safety of hepatic pedicle occlusion with the Pringle maneuver during difficult LC. From 2011 to 2015, LC with hepatic pedicle occlusion by the Pringle maneuver was performed in 67 patients (Pringle group). Another group of 67 cases with matched clinical parameters where LC was performed without the Pringle maneuver (non-Pringle group) was retrieved from a database to serve as the control group. The Pringle group had a significantly lower conversion rate (1.49% vs. 11.9%; P = 0.038), less blood loss (37.5 ± 24.1mL vs. 94.5 ± 67.8mL; P = 0.002), shorter postoperative hospitalization (2.5 ± 1.4days vs. 3.5 ± 2.5days; P = 0.005), and lower cost ($1343 ± $751 USD vs. $1674 ± $609 USD; P = 0.024) than non-Pringle group. There was one case each of bile duct injury and readmission within 30days because of bile leakage in the non-Pringle group, but none in the Pringle group. Hepatic pedicle occlusion could provide a clear surgical field and enable the recognition of structures during LC. The Pringle maneuver offers a feasible and safe approach to lower conversion rates in difficult LC.

Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway.

Oxidative and nitrosative stress-induced endothelial cell damage play an essential role in the pathogenesis of hepatic ischemia-reperfusion (IR) injury. IR is associated with reduced eNOS expression and exacerbated by superimposed stress. NOSTRIN induces intracellular endothelial nitric oxide synthase (eNOS) translocation and inducible nitric oxide synthase (iNOS) increases nitric oxide (NO) production. Our aim was to assess hepatic expression of iNOS, eNOS, and NOSTRIN in IR with or without N-acetylcysteine (NAC) or thymoquinone (TQ) pretreatment and to compare their hepatoprotective effects. Surgical induction of IR was performed by occlusion of hepatic pedicle for 30min with mini-clamp and reperfused for 30min. The effects of TQ (20mg/kg/day) or NAC (300mg/kg/day) administered orally for 10days were evaluated by serum ALT and AST, oxidative stress parameters, NO production, and histopathological analysis. Also, localization and expression of iNOS, eNOS, and NOSTRIN were assessed by immunofluorescence. TQ or NAC pretreatment significantly decreased elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and myeloperoxidase (MPO) activities, malondialdehyde (MDA) level, and NO production. In addition, they restored the depleted GSH content and alleviated histopathological changes. Furthermore, they up-regulated eNOS and down-regulated iNOS and NOSTRIN expressions. TQ exerts its hepatoprotective effect, at least in part, by nitric oxide signaling pathway through modulation of iNOS, eNOS, and NOSTRIN expressions as well as suppression of oxidative stress.

Postoperative biological and clinical outcomes following uncomplicated pancreaticoduodenectomy.

Backgrounds/AimsThe aim of this study was to describe clinical and biological changes in a group of patients who underwent pancreaticoduodenectomy (PD) without any complication during the postoperative period. These changes reflect the "natural history" of PD, and a deviation should be considered as a warning sign.MethodsBetween January 2000 and December 2009, 131 patients underwent PD. We prospectively collected and retrospectively analyzed demographic data, pathological variables, associated pathological conditions, and preoperative, intraoperative, and postoperative variables. Postoperative variables were validated using an external prospective database of 158 patients.ResultsThe mean postoperative length of hospital stay was 20.3±4 days. The mean number of days until removal of nasogastric tube was 6.3±1.6 days. The maximal fall in hemoglobin level occurred on day 3 and began to increase after postoperative day (POD) 5, in patients with or without transfusions. The white blood cell count increased on POD 1 and persisted until POD 7. There was a marked rise in aminotransferase levels at POD 3. The peak was significantly higher in patients with hepatic pedicle occlusion (866±236 IU/L versus 146±48 IU/L; p<0.001). For both γ-glutamyl transpeptidase and alkaline phosphatase, there was a fall on POD1, which persisted until POD 5, followed with a stabilization. Bilirubin decreased progressively from POD 1 onwards.ConclusionsThis study facilitates a standardized biological and clinical pathway of follow-up. Patients who do not follow this recovery indicator could be at risk of complications and additional exams should be made to prevent consequences of such complications.

Quercetin modulates iNOS, eNOS and NOSTRIN expressions and attenuates oxidative stress in warm hepatic ischemia-reperfusion injury in rats

The pathogenesis of hepatic ischemia/reperfusion (I/R) is mediated through the generation of oxidative and nitrosative stress-induced cell injury. Hence, the present study was designed to evaluate the hepatoprotective effect of quercetin (QR) compared to N-acetylcysteine (NAC) against hepatic I/R injury in rats and to assess iNOS, eNOS and NOSTRIN protein expressions, as a possible mechanism of its hepatoprotective effect. Hepatic ischemia was surgically performed by occlusion of hepatic pedicle (hepatic artery, portal vein, bile duct) that supplies the left and medial lobes (approximately 70% of the total liver mass), for 30 min with a vascular clamp followed by releasing the clamp and the liver was reperfused for 30 min. QR-pretreatment increased eNOS protein expression with simultaneous decrease in iNOS and NOSTRIN protein expressions. It also decreased serum aspartate aminotransferase (AST), alanine aminotransferases (ALT) and hepatic myeloperoxidase (MPO) activities. In addition, it restored the depleted content of reduced glutathione (GSH) and decreased malondialdehyde (MDA) and nitric oxide (NO) levels. A notable finding is that QR alleviated I/R-induced histopathological changes. Therefore, the present study illustrates the hepatoprotective effect of quercetin compared to N-acetylcysteine against ischemia/reperfusion-induced liver injury by inhibiting oxidative stress and by modulating iNOS, eNOS and NOSTRIN protein expressions.

Intestinal translocation of clinical isolates of vancomycin-resistant Enterococcus faecalis and ESBL-producing Escherichia coli in a rat model of bacterial colonization and liver ischemia/reperfusion injury.

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×1010 cfu and ESBL-E. coli: 1.12×1010 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups. Systemic blood endotoxin levels were higher in the group with complete hepatic ischemia.

The Effects of Remote Ischemic Preconditioning and N-Acetylcysteine with Remote Ischemic Preconditioning in Rat Hepatic Ischemia Reperfusion Injury Model

Background. Remote ischemic preconditioning (RIP) and pharmacological preconditioning are the effective methods that can be used to prevent ischemia reperfusion (IR) injury. The aim of this study was to evaluate the effects of RIP and N-Acetylcysteine (NAC) with RIP in the rat hepatic IR injury model. Materials and Methods. 28 rats were divided into 4 groups. Group I (sham): only laparotomy was performed. Group II (IR): following 30 minutes of hepatic pedicle occlusion, 4 hours of reperfusion was performed. Group III (RIP + IR): following 3 cycles of RIP, hepatic IR was performed. Group IV (RIP + NAC + IR): following RIP and intraperitoneal administration of NAC (150 mg/kg), hepatic IR was performed. All the rats were sacrificed after blood samples were taken for the measurements of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver was processed for conventional histopathology. Results. The hepatic histopathological injury scores of RIP + IR and RIP + NAC + IR groups were significantly lower than IR group (P = 0.006, P = 0.003, resp.). There were no significant differences in AST and ALT values between the IR, RIP + IR, and RIP + NAC + IR groups. Conclusions. In the present study, it was demonstrated histopathologically that RIP and RIP + NAC decreased hepatic IR injury significantly.

Beneficial effects of S-adenosyl-L-methionine on post-hepatectomy residual liver function: a prospective, randomized, controlled clinical trial.

Hepatectomy is associated with high rates of postoperative liver dysfunction in patients with cirrhosis. Since S-adenosyl-L-methionine (SAMe) can be used to treat liver disease, we performed a prospective clinical trial to investigate whether it could be used after hepatectomy to benefit residual liver function. We studied 79 hepatitis-related chronic patients who underwent resection of hepatocellular carcinoma; 39 patients were randomly assigned to receive postoperative intravenous SAMe treatment, and 40 were randomly assigned to a control group. The postoperative SAMe treatment consisted of SAMe 1,000mg given intravenously for seven days. The other treatment was standardized. At inclusion into the trial no significant differences were observed between the two groups with respect to gender, age, Child classification, preoperative liver function tests, blood loss, total time of hepatic pedicle occlusion and the extent of liver resection. The overall frequency of postoperative liver insufficiency decreased from 42% in the control group to 31% in the SAMe group, although not statistically significant (p=0.121). When the patients who underwent hepatic pedicle occlusion by Pringle’s maneuver over 15min were analyzed, the frequency of postoperative liver insufficiency (p=0.028), serum total bilirubin levels on days 5 (p=0.025) and 7 (p=0.032) preoperatively, and the maximum value of postoperative serum total bilirubin (p=0.040) were significantly greater in the control than in the SAMe group. The results indicate that the postoperative SAMe therapy can benefit residual liver function of the patients with cirrhosis, especially in those suffering greater ischemia reperfusion injury.

Ischemic preconditioning attenuates remote pulmonary inflammatory infiltration of diabetic rats with an intestinal and hepatic ischemia-reperfusion injury

To assess ischemic preconditioning (IPC) effects in pulmonary lesion in intestinal and hepatic ischemia-reperfusion (IR) injury models using diabetic rats. Diabetes (DM) was induced in 28 male Wistar rats by alloxan (42 mg/kg, IV). After 28 days, severe DM rats were submitted to intestinal or hepatic IR injury with or without IPC. Intestinal IR (30 min of mesenteric artery occlusion and 30 min of reperfusion; n=6) and IPC groups (10 min ischemia, 10 min reperfusion, followed by intestinal IR; n=6), and Hepatic IR (30 min of hepatic pedicle occlusion and 30 min of reperfusion; n=5) and IPC groups (10 min ischemia, 10 min reperfusion, followed by hepatic IR; n=5), were compared to DM rats group (n=6). Plasmatic lactate, glycemia were measured before and after IR injury. Histomorphology of lung was performed counting inflammatory cells. Data was expressed in mean± SE. P<0.05. Glycemia and lactate were similar among groups. IPC did not interfere in these parameters. On histological evaluation, IR increased inflammatory cells infiltration in pulmonary parenchyma compared to control in both IR injury models. IPC attenuated inflammatory infiltration in lungs. Ischemic preconditioning protects against remote ischemia-reperfusion injury in lung on intestinal or hepatic ischemia-reperfusion model with acute diabetes.

Impact of mesocaval shunt on safe minimal liver remnant: Porcine model

To investigate the capacity of shunts to relieve portal hypertension and decrease the safe minimal liver remnant in pigs. A subtotal hepatectomy with < 60 mL blood loss and without hepatic pedicle occlusion was performed. The mesenteric venous inflow was diverted through a mesocaval shunt (MCS) constructed using the prepared left renal vein with an end-to-side running suture of 5-0 proline. All 21 animals that underwent subtotal hepatectomy and/or MCS were divided into three groups. In the 15% group, the residual volume was 14%-19% of total liver volume (TLV); in the 15%+ S group, the residual volume was also 14%-19% of TLV with a mesocaval shunt (MCS); and in the 10%+ S group, the residual volume was 8%-13% of TLV with an MCS. In the three groups, the intraoperative portal vein pressure (PVP) and portal vein flow (PVF) were monitored and compared at laparotomy and 1 h post-hepatectomy. The survival rate, sinusoidal endothelial damage, tissue analysis, and serum analysis were investigated among the three groups. The percentage residual liver volume was 15.9%, 16.1% and 11.8% in the 15%, 15%+ S, 10%+ S groups, respectively. After hepatectomy, PVF and portal-to-arterial flow ratio in the 15%+ S group significantly decreased and hepatic artery flow (HAF) per unit volume significantly increased, compared to those in the 15% group. The PVP in the 15%+ S group and 10%+ S group increased slightly from that measured at laparotomy; however, in the 15% group, the PVP increased immediately and significantly above that observed in the other two groups. The 14-d survival rates were 28.5%, 85.6%, and 14.2% in the 15%, 15%+ S, and 10%+ S groups, respectively. In the 15%+ S group, the shunts effectively attenuated injury to the sinusoidal endothelium, and the changes in the serum and tissue analysis results were significantly reduced compared to those in the 15% and 10%+ S groups. MCS can decompress the portal vein and so attenuate liver injury from hyperperfusion, and make extreme or marginal hepatectomy safer.

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine.

To study the effect of H2 gas on liver injury in massive hepatectomy using the intermittent Pringle maneuver in swine. Male Bama pigs (n = 14) treated with ketamine hydrochloride and Sumianxin II as induction drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups: Hydrogen-group (n = 7), the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; contrast-group (n = 7), underwent 70% hepatotectomy without inhalation of hydrogen. Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) in liver tissue were measured at pre-operation, post-hepatotectomy (PH) 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine. There were no significant differences in body weight, blood loss and removal liver weight between the two groups. There was no significant difference in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in contrast-group at PH 3 h, although there were no significant difference (P = 0.655). ALT and AST in Hydrogen-group was significantly lower comparing to contrast-group (P = 0.036, P = 0.011, vs. P = 0.032, P = 0.013) at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH 1 h and 3 h. In the hydrogen gas treated-group, the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group (P = 0.0005, P = 0.0004). In Hydrogen-group, the HA level was also significantly low to contrast-group (P = 0.0005, P = 0.0005) although the two groups all increased at PH 1 h and 3 h. The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group. However, PCNA index (%) was not statistically significant between the two groups (P = 0.802). Microphotometric evaluation of apoptotic index (AI) in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h, the AI% level in the hydrogen was significantly low to contrast-group (P = 0.012). There were no significant difference between Hydrogen-group and contrast-group at pre-operation (P = 0.653, P = 0.423), but after massive hepatotectomy, the TNF-α and IL-6 levels increase, and its in Hydrogen-group was significantly low compared with contrast-group (P = 0.022, P = 0.013, vs. P = 0.016, P = 0.012), respectively. Hydrogen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis. H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy, possibly by the reduction of inflammation and oxidative stress, maybe a potential agent for treatment in clinic.

Extended hepatic pedicle occlusion in major hepatectomy for primary liver cancer

To evaluate the influence of extended hepatic pedicle occlusion (HPO) on hepatic ischemic/reperfusion (I/R) injury and intraoperative blood loss in major hepatectomy for primary liver cancer (PLC). Between June 2001 and December 2005, a total number of 843 patients with PLC had been operated on. Those whose hepatic pedicle were occluded continuously for or longer than 30 min during hepatectomy were retrospectively reviewed (continuous HPO group) and compared to the patients whose hepatic pedicle were occluded for the same length of time but intermittently (intermittent HPO group). The amount of intraoperative blood loss, the percentage of the patients who needed blood transfusion and postoperative liver biochemical tests were compared between the two groups. There were 35 cases in continuous HPO group and 38 cases in intermittent HPO group with occlusion time between 30 min and 45 min. The two groups were matched for underlying liver disease ,preoperative liver function, tumor size and location, major intrahepatic vessel involvements and the types and extensions of the hepatectomies. The mean intraoperative blood loss in continuous HPO group was significantly less than that in intermittent HPO group (660 ml vs. 1054 ml, P < 0.05); accordingly, the percentage of patients who need blood transfusion in continuous HPO group was significantly lower than that in intermittent HPO group (48.6% vs. 78.9%, P < 0.01). Patients in both of the groups were recovered smoothly after operation, with no occurrence of liver failure. The hepatic pedicle can be continuously occluded for 3045 min in cirrhotic patients with well compensated liver function, and when compared to routine intermittent HPO, continuous HPO significantly decreases the intraoperative blood loss and reduces the need for transfusion. Meanwhile it does not increase the hepatic I/R injury.

Effects of nimodipine and pentoxyfylline in prevention of hepatic ischemic damage in rats at normal and hypothermic conditions

Hepatic ischemia should be considered in serious liver injury, liver tumor resection and liver transplantation. There are other conditions that decrease hepatic blood flow and cause hepatic ischemia, such as hemorrhagic shock, sepsis, hepatic artery ligation, trauma, and certain vascular lesions. In this study, effects of nimodipine (a calcium channel blocker) and pentoxyfylline (a derivative of methylxanthine) on duration and degree of hepatic ischemia in rats at normothermic and hypothermic conditions are investigated. This study was performed on 6 groups of Wistar Albino type rats, each group consisting of 7 rats. Groups were separated into normothermic (A) and hypothermic (B) conditions AI—Control group, AII—Nimodipine group and AIII—Pentoxyfylline group, B IV—Control group, BV—Nimodipine group and BVI—Pentoxyfylline group respectively. After hepatic pedicle occlusion lasting 45 min, blood samples were drawn from the rats for evaluation of alanine aminotransferase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) values. Moreover, hepatic biopsies were taken to assess pathological changes under electron microscopy. These changes were evaluated through a grading system. As a result; it has been shown that both nimodipine and pentoxyfylline delayed effects of hepatic ischemia in a statistically significant manner in comparison with the control group and these effects were found to be more significant in hypothermic conditions.