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Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ's post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with "global" consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion.

Background: The aim of this study was to compare ischemic preconditioning with the intermittent vascular occlusion technique in liver resections performed under inflow and outflow occlusion., Methods: Fifty-four patients with resectable liver tumors assigned were randomly to undergo surgery with either ischemic preconditioning (IP group, n = 27) or with intermittent vascular occlusion (IVO group, n = 27). Both groups were compared regarding surgical parameters, aspartate transaminase levels, and apoptosis., Results: For warm ischemic time less than 40 minutes, no significant difference was noticed between the 2 groups apart from caspase-3 activity, which was higher in the IVO group than in the IP group (17.2 +/- 3.4 vs. 10.3 +/- 5.2, P < .05). When warm ischemia exceeded 40 minutes, the IP group showed higher levels in blood aspartate transaminase levels on day 3 (442 +/- 178 IU/L vs. 305 +/- 104 IU/L, P < .05) and higher caspase-3 levels (26.5 +/- 5.7 count/high-power field [hpf] vs. 20.7 +/- 3.6 count/hpf, P < .05) and apoptotic activity (28.5 +/- 7.5 count/hpf vs. 20.2 +/- 4.1 count/hpf, P < .05), as compared with the IVO group., Conclusions: Although both techniques showed comparable efficacy for short ischemic times, intermittent vascular occlusion provided better cytoprotection when ischemia exceeded 40 minutes.

Ischemic preconditioning (IPC) and intermittent vascular control (IVC) have been shown to reduce the number of ischemia/reperfusion injuries during liver resections with the Pringle maneuver. Our study aimed to compare the beneficial effect of these two modalities in relation to the duration of normothermic liver ischemia. A group of 24 Landrace pigs with a mean body weight of 25 to 30 kg were subjected to extended liver resection of more than 65%. Although, 12 animals underwent IPC (10 minutes of ischemia and 10 minutes of reperfusion), and subsequently the Pringle maneuver was applied for 90 minutes (n= 6) or 120 minutes (n= 6). Another 12 animals underwent liver resection by IVC (20 minutes of ischemia alternated with 5 minutes of reperfusion) for 60 minutes (n = 6) or 120 minutes (n = 6) of inflow vascular control. At 90 minutes of liver ischemia, the IPC group demonstrated lower levels of asportate aminotransferase (AST) (173 +/- 53 vs. 265 +/- 106 IU; p =0.089) and malondialdehyde (MDA) (2.60 +/- 1.03 vs. 5.33 +/- 2.25 micromol/L; p =0.022) and higher liver tissue cAMP (200 +/- 42 vs. 146 +/- 40 pmol/g wet wt, p = 0.04) compared to the IVC group. However, no pathologic differences were observed between the two groups. By contrast, at 120 minutes of liver ischemia, IVC proved to be more beneficial, reflected by lower levels of AST (448 +/- 135 vs. 857 +/- 268 IU; p = 0.006) and MDA (8.33 +/- 1.75 vs. 12.7 +/- 4.31 micromol/L; (p = 0.045), a higher cAMP level (127 +/- 10 vs. 97 +/- 31 pmol/g wet wt p = 0.045), and eventually less cellular necrosis (necrosis score 1.66 +/- 0.51 vs. 2.85 +/- 1.16; p = 0.04) compared to the IPC group. It appears that IPC should be employed when liver ischemia is anticipated to last less than 90 minutes, followed by IVC when the liver ischemia is expected to last 120 minutes.

Purpose: Central hepatectomy is a complex, parenchymal-sparing procedure which has been associated with increased blood loss, prolonged operating time, and increased duration of remnant hypoxia. In this report, we compare two different techniques of vascular control, namely sequential hemihepatic vascular control (SHHVC) and selective hepatic vascular exclusion (SHVE) in central hepatectomies. Methods: From January 2000 to September 2011, 36 consecutive patients underwent a central hepatectomy. SVHE was applied in 16 consecutive patients, and SHHVC was applied in 20 patients. Both groups were comparable regarding their demographics. Results: Total operative time and morbidity rates were similar in both groups. Warm ischemia time was significantly longer in SVHE patients (46 min vs 28 min, p = 0.03). Total blood loss and number of transfusions per patient were also higher in the SVHE group (650 vs. 400 mL, p = 0.04 and 2.2 vs. 1.2 units, p = 0.04, respectively). AST values were significantly higher in SVHE on days 1 and 3 compared to SHHVC patients (650 vs. 400, p = 0.04 and 550 vs. 250, p = 0.001, respectively). Conclusion: Sequential hemihepatic vascular control is a safe technique for central hepatectomies. Decreased intraoperative blood loss and transfusions and attenuated liver injury are the main advantages of this approach. [ABSTRACT FROM AUTHOR]

Introduction: Ischemia-reperfusion (I-R) injury has long been regarded a primary factor for the physiological dysfunction that can occur following major liver resection performed under vascular control. The aim of our study was to assess the effect of treatment with desferoxamine (DFO), a potent antioxidative agent, monitoring the I-R injury on a porcine model of major hepatectomy. Materials and Methods: Twelve female pigs were allocated to control ( n == 6) and DFO groups ( n == 6) and underwent 30 min of liver ischemia, during which a ≥≥30%% hepatectomy was performed, followed by six hours of postoperative monitoring. The DFO group animals were preconditioned with a continuous iv solution of DFO to a total dose of 100 mg/kg during their postoperative period. Liver remnants (≈≈70%% of initial liver volume) were evaluated by means of infrared spectroscopy, serum lactate measurement of the systemic, portal and hepatic vein blood, and by immunohistochemical assessment of apoptosis in consecutive liver biopsies. Results: DFO group demonstrated considerably faster restoration of tissue oxygenation (92.33%% vs. 80%%, p < .05) and serum lactate values (1.23 mmol/l vs. 2.27 mmol/l, p < .05). Moreover, apoptosis as estimated by TUNEL and caspase-3 staining was significantly lower in the DFO group (0.06%% vs. 1.17%% and 1.17%% vs. 2%%, respectively, p < .05). The severity of the I-R injury showed a linear correlation to the restoration of tissue oxygenation, as estimated by infrared-spectroscopy ( r2 == 0.81, p < .01). Conclusion: Iron chelation with DFO appears to attenuate I-R injury of the liver remnant following hepatectomy, as reflected by faster restoration of tissue oxygenation and lower apoptotic activity. [ABSTRACT FROM AUTHOR]

Ischemic preconditioning is one of the therapeutic interventions aiming at preventing ischemia/reperfusionrelated injury. Numerous experimental studies and a few clinical series have shown that during liver resections, ischemic preconditioning is a promising strategy for optimizing the postoperative outcome. Moreover, various types of pharmacological intervention as well as different types of preconditioning, such as remote preconditioning, the use of heat shock, and hyperbaric oxygen, have been developed to attenuate the functional impairment accompanying ischemia/reperfusion injury. This review summarizes the various forms of preconditioning, thus suggesting that close cooperation between surgeons and anesthesiologists paves the way to apply novel strategies to improve the outcome of liver resection. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated lactate release by the liver itself in hepatectomies performed under selective hepatic vascular exclusion. We hypothesized that ischemic preconditioning applied in this setting might lead to a reduction of hepatic lactate production.Methods: Twenty-one patients underwent hepatectomy under inflow and outflow occlusion combined with ischemic preconditioning (IP group, n = 21). These patients were matched 1:1 with patients subjected to the same technique of hepatectomy under vascular occlusion without ischemic preconditioning (control group, n = 21). The transhepatic lactate gradient (hepatic vein-portal vein) was calculated before liver dissection and 60 min post-reperfusion.Results: In the control group, the transhepatic lactate gradient before liver resection was negative indicating consumption by the liver. After 60 min post-reperfusion, this gradient became positive, indicating net lactate production by the liver (0.2 ± 0.3 vs. -0.3 ± 0.2 mmol/L, P < 0.001). In the IP group, the liver consumed lactate both before resection and 60 min post-reperfusion (gradients -0.2 ± 1.1 and -0.1 ± 0.6 mmol/L, respectively). The magnitude of lactate release by the liver correlated with systemic hyperlactatemia post-reperfusion and 24 h postoperatively (r(2) = 0.54, P < 0.001 and r(2) = 0.67, P < 0.001, respectively). Significant correlations between the transhepatic lactate gradient post-reperfusion and peak postoperative AST as well as the apoptotic response of the liver remnant were also demonstrated (r(2) = 0.72, P < 0.001 and r(2) = 0.66, P < 0.001, respectively).Conclusion: The microcirculatory derangement and cellular aerobic metabolism breakdown elicited by ischemia-reperfusion insults can be prevented with hepatoprotective measures such as ischemic preconditioning. The transhepatic lactate gradient could act as a monitoring and prognostic tool of the efficacy of ischemic preconditioning. [ABSTRACT FROM AUTHOR]

Liver resections are frequently associated with significant ischemia-reperfusion (I-R) injury of the liver remnant. The aim of this study was to investigate whether deferoxamine (DFO) can ameliorate I-R injury during major hepatectomies performed under vascular exclusion of the liver in a porcine model. Twelve female domestic pigs were divided into control (n = 6) and DFO treatment (n = 6) groups and subjected to 150 min. liver ischemia followed by 70% hepatectomy and 24 hours reperfusion. Pigs in the DFO group received a continuous intravenous infusion of 100 mg/kg DFO. Liver remnant injury was evaluated by liver function tests, hepatic histology as well as serum and liver tissue malondialdehyde (MDA) concentrations. Deferoxamine-treated animals had reduced total bilirubin, γ-glutamyl transferase and ammonia levels as well as hepatocyte necrosis and oxidative injury. In a subsequent randomized clinical trial using DFO for I-R protection during major liver surgery, preliminary results revealed amelioration of hepatocellular damage, oxidative and inflammatory serum markers and apoptotic response in liver remnant biopsies. [ABSTRACT FROM AUTHOR]

Extensive experimental studies and a few clinical series have shown that ischemic preconditioning (IPC) attenuates oxidative ischemia/reperfusion (I/R) injuries in liver resections performed under inflow vascular control. Selective hepatic vascular exclusion (SHVE) employed during hepatectomies completely deprives the liver of blood flow, as it entails simultaneous clamping of the portal triad and the main hepatic veins. The aim of the present study was to identify whether IPC can also protect hepatocytes during liver resections performed under SHVE. Patients undergoing major liver resection were randomly assigned to have either only SHVE (control group, n = 43) or SHVE combined with IPC—10 min of ischemia followed by 15 min of reperfusion before SHVE was applied (IPC group, n = 41). The two groups were comparable with regard to age, liver resection volume, blood loss and transfusions, warm ischemic time, and total operative time. In liver remnant biopsies obtained 60 min post-reperfusion, IPC patients had significantly fewer cells stained positive by TUNEL compared to controls (19% ± 8% versus 45% ± 12%; p < 0.05). Also IPC patients had attenuated hepatocyte necrosis, systemic inflammatory response, and oxidative stress as manifested by lower postoperative peak values of aspartate transaminase, interleukin-6, interleukin-8, and malondialdehyde compared to controls. Morbidity was similar for the two groups, as were duration of intensive care unit stay and extent of total hospital stay. In major hepatectomies performed under SHVE, ischemic preconditioning appears to attenuate apoptotic response of the liver remnant, possibly through alteration of inflammatory and oxidative pathways. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to retrospectively analyze risk factors, diagnosis and management of gastrointestinal (GI) complications following cardiac operations. Methods: Patients who developed GI complications after a cardiac operation were studied. Anesthesia protocols, techniques of cardiac surgery, potential risk factors, complications and medical and surgical interventions were reviewed and analyzed. Results: Out of 3,724 consecutive patients undergoing heart operations during an 8-year period, 33 patients developed GI complications. Eleven patients developed ischemic colitis, 8 cholecystitis, 6 GI bleeding, 4 liver failures, 3 pancreatitis and 1 esophageal hernia. Patients with GI complications had a lower mean ejection fraction compared to patients not developing these complications (45.1 vs. 49.7%, p < 0.01). Also, patients undergoing an urgent cardiac operation were significantly more likely (3.49 times more likely) to develop GI complications postoperatively. Of the 33 affected patients, 18 were treated conservatively and 15 underwent an emergency exploratory laparotomy. Overall mortality was 12% (4 patients). Conclusions: Intestinal ischemia and cholecystitis appear to be the most frequent GI complications associated with cardiac surgery. Risk factors include a low ejection fraction and an urgent cardiac operation. Early recognition and treatment of these complications may reduce mortality. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Ischemic preconditioning (IPC) and intermittent vascular control (IVC) have been shown to reduce the number of ischemia/reperfusion injuries during liver resections with the Pringle maneuver. Our study aimed to compare the beneficial effect of these two modalities in relation to the duration of normothermic liver ischemia. A group of 24 Landrace pigs with a mean body weight of 25 to 30 kg were subjected to extended liver resection of more than 65%. Although, 12 animals underwent IPC (10 minutes of ischemia and 10 minutes of reperfusion), and subsequently the Pringle maneuver was applied for 90 minutes (n = 6) or 120 minutes (n = 6). Another 12 animals underwent liver resection by IVC (20 minutes of ischemia alternated with 5 minutes of reperfusion) for 60 minutes (n = 6) or 120 minutes (n = 6) of inflow vascular control. At 90 minutes of liver ischemia, the IPC group demonstrated lower levels of asporate aminotransferase (AST) (173 ± 53 vs. 265 ± 106 IU; p = 0.022) and higher liver tissue cAMP (200 ± 1.03 vs. 5.33 ± 2.25 μmol/L; p = 0.022) and higher liver tissue cAMP group. However, no pathologic differences were observed between the two groups. By contrast, at 120 minutes of liver ischemia, IVC proved to be more beneficial, reflected by lower levels of AST (448 ± 135 vs. 857 ± 268 IU; p = 0.006) and MDA (8.33 ± 1.75 vs. 12.7 ± 4.31 μmol/L; (p = 0.045), a higher cAMP level (127 ± 10 vs. 97 ± 31 pml/g wer wt p = 0.045), and eventually less cellular necrosis (necrosis score 1.66 ± 0.51 vs. 2.85 ± 1.16; p = 0.04) compared to the IPC group. It appears that IPC should be employed when liver ischemia is anticipated to last less than 90 minutes, followed by IVC when the liver ischemia is expected to last 120 minutes. [ABSTRACT FROM AUTHOR]

The aim of our study is to assess the effect of extrahepatic ipsilateral portal vein branch ligation in hepatectomies conducted under selective hepatic vascular exclusion with sharp transection of the liver parenchyma. Twenty-six patients (Group A) underwent major hepatectomy from January 2007 to December 2009, and hemostasis was achieved by ligation of the ipsilateral portal vein branch in addition to suture ligation of the cut surface vessels. A control group (Group B) was composed of 26 matched patients picked from our hospital's database, in which hemostasis was achieved by suture ligation of the cut surface vessels only. Warm ischemia time, intraoperative blood loss, blood transfusions, and liver function were compared. Reduced blood loss (450 vs 680 mL, P 5 0.03), less transfusions (8 vs 20% of the patients, P 5 0.04), and decreased warm ischemia time (34 vs 42 minutes, P 5 0.04) were observed in Group A. Extrahepatic ligation of the ipsilateral portal vein branch is simple, safe, and effective in reducing blood loss and warm ischemia time in major hepatectomies performed under selective vascular exclusion. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion (I/R) injury is one of the main factors affecting the function and structure of small bowel transplantation (SBT), by generation of proinflammatory mediators such as reactive oxygen species, reactive nitrogen species, cytokines, and endotoxin. Experimental data have demonstrated that N-acetylcysteine (NAC) attenuates intestinal I/R injury. The objective of this study was to determine the effect of NAC preconditioning on the SBT-I/R induced inflammatory cascade, with particular focus on TNF, IL-8, hyaluronic acid, and NO. Methods: Fifteen domestic pigs were used as donors. Fifteen recipient animals were randomly assigned into two groups. Group 1: SBTx (n =7) served as controls and Group 2: SBTx (n =8) served as the experimental group (NAC administration). Results: NAC administration at a continuous 4h intravenous bolus dose of 200mg/kg of body weight, starting before initiation of bowel transplantation, resulted in statistically significant (P <0.05) higher plasma levels of NO, and lower plasma levels of hyaluronic acid, TNF-α, IL-8, and LDH compared with those of the control group, at the 360min time point. Conclusions: NAC confers a protective role in small bowel transplantation associated, partly, with NO generation and hyaluronic acid, TNF-α and IL-8 amelioration. [ABSTRACT FROM AUTHOR]

Background: Numerous previous studies have established the hepatoprotective properties of N-acetylcysteine (NAC). The present study was designed to investigate the effects of NAC on a warm hepatic ischemia–reperfusion rat model with a focus on the role of cAMP. Materials and methods: Fifty-six male Wistar rats were allocated randomly into the control group (n = 28) or the study group (group NAC, n = 28). Group NAC animals received an intravenous bolus dose of 0.3 mg/g NAC, whereas control animals were given an equal volume of normal saline. Subsequently, 60-min partial liver ischemia was induced by occlusion of blood inflow to the left and middle liver lobes. Aspartate aminotransferase, alanine aminotransferase, and α-glutathione S-transferase levels, platelet aggregation, and ischemic tissue cyclic adenosine 5-monophosphate (cAMP) levels were examined at 30, 60, and 120 min after reperfusion. Parts of the ischemic liver were sampled at the same time-points. Measurements were obtained from seven animals at each time point. Results: The administration of NAC resulted in lower levels of aspartate aminotransferase, alanine aminotransferase, and α-glutathione S-transferase, decreased platelet aggregation, and increased levels of ischemic tissue cAMP at all time points after reperfusion. Histologically, fewer necrotic changes were observed in the NAC group at 60 and 120 min after reperfusion. All differences were statistically significant (P < 0.05). Conclusions: In the present study, NAC seems to attenuate hepatic ischemia–reperfusion damage, as demonstrated by liver function tests and liver histology. The effects of NAC appear to be mediated by the decrease in platelet aggregation and increase in the levels of cAMP observed in ischemic liver tissue. [Copyright &y& Elsevier]