Left Lateral Lobe Of Liver Research Articles

Establishing Nd:YAG Laser-based Left Lateral Liver Resection

Aim of this study was to assess the feasibility and safety of a 1064 nm Nd:YAG laser for left lateral liver resection in a porcine model. Laparoscopy and hand-assisted laparoscopic surgery were evaluated and compared with conventional open surgery. Animals were randomized for open, hand assisted, and laparoscopic left lateral liver lobe resection. Primary endpoints were intraoperative blood loss, dissection time, laboratory changes, and abdominal wall adhesions. In addition intraoperative cardiopulmonary data, postoperative clinical parameters, and necropsy findings were analyzed. Liver resection was successful in all animals without intraoperative or postoperative mortality. Laparoscopic dissection time was significantly increased. Average blood loss was 340 mL for open surgery and 320 mL for hand-assisted surgery. Blood loss during laparoscopy was significantly smaller with a mean of 180 mL. Postmortem findings revealed extensive adhesions for open surgery whereas hand assisted and laparoscopic animals showed limited adhesions in the upper abdomen. Nd:YAG laser-based liver resection is a potentially safe and feasible technique. The minimal access approaches show comparable results to the open technique with reduced abdominal trauma and less adhesions. Laparoscopy was more time consuming but showed reduced blood loss compared with both other groups.

Technical requirements for effective regional hydrodynamic gene delivery to the left lateral lobe of the rat liver

Hydrodynamic gene delivery to the liver is an attractive approach for clinical liver gene therapy, but critical aspects of technique remain uncertain. There has not been to date any report of high levels of hydrodynamic gene delivery to the liver, except in rodents. Regional hydrodynamic delivery to individual lobes/segments of the liver is being pursued in preclinical pig models, where reporter gene expression has been <1% of rodent levels, and in one clinical study, where there was no substantive evidence of gene expression. In none of these studies did surgical technique include outflow obstruction of the DNA solution. Here we report a novel technique for regional hydrodynamic gene delivery to the left lateral lobe of the rat liver. The technique gives high levels of gene delivery specific to the left lateral lobe with low volumes ( approximately 1.5 ml) of DNA solution, and permits an evaluation of hydrodynamic delivery in the presence and in the absence of outflow obstruction. We report that outflow obstruction is an absolute requirement for effective hydrodynamic gene delivery to individual lobes/segments of the liver, and therefore that minimally invasive techniques will not be possible in the clinic.

Loss or Silencing of the PHD1 Prolyl Hydroxylase Protects Livers of Mice Against Ischemia/Reperfusion Injury

Liver ischemia/reperfusion (I/R) injury is a frequent cause of organ dysfunction. Loss of the oxygen sensor prolyl hydroxylase domain enzyme 1 (PHD1) causes tolerance of skeletal muscle to hypoxia. We assessed whether loss or short-term silencing of PHD1 could likewise induce hypoxia tolerance in hepatocytes and protect them against hepatic I/R damage. Hepatic ischemia was induced in mice by clamping of the portal vessels of the left lateral liver lobe; 90 minutes later livers were reperfused for 8 hours for I/R experiments. Hepatocyte damage following ischemia or I/R was investigated in PHD1-deficient (PHD1(-/-)) and wild-type mice or following short hairpin RNA-mediated short-term inhibition of PHD1 in vivo. PHD1(-/-) livers were largely protected against acute ischemia or I/R injury. Among mice subjected to hepatic I/R followed by surgical resection of all nonischemic liver lobes, more than half of wild-type mice succumbed, whereas all PHD1(-/-) mice survived. Also, short-term inhibition of PHD1 through RNA interference-mediated silencing provided protection against I/R. Knockdown of PHD1 also induced hypoxia tolerance of hepatocytes in vitro. Mechanistically, loss of PHD1 decreased production of oxidative stress, which likely relates to a decrease in oxygen consumption as a result of a reprogramming of hepatocellular metabolism. Loss of PHD1 provided tolerance of hepatocytes to acute hypoxia and protected them against I/R-damage. Short-term inhibition of PHD1 is a novel therapeutic approach to reducing or preventing I/R-induced liver injury.

Budd-Chiari-like Syndrome in a Dog Due to Liver Lobe Entrapment Within the Falciform Ligament

A 13-year-old, spayed female golden retriever was referred for further evaluation of ascites, characterized as a modified transudate, detected after an episode of acute collapse. Prior to referral, the dog was treated for suspected right-sided heart failure and developed ventricular tachycardia. On referral, echocardiography ruled out cardiac causes for the effusion, and following stabilization the dog was taken to surgery for abdominal exploration. Surgery revealed entrapment of the left lateral liver lobe within the falciform ligament. Surgical removal of the entrapped liver lobe and falciform fat resulted in resolution of the Budd-Chiari-like syndrome. No abdominal effusion was seen on follow-up ultrasound examination. This is the first reported case of Budd-Chiari-like syndrome caused by liver lobe entrapment within falciform fat that was successfully corrected with surgery.

Evaluation of Laparoscopic Liver Resection with Two Different Nd:YAG Lasers for Future Use in a High-Field Open MRI

Laparoscopic liver surgery is a safe and feasible technique for the treatment of benign and malignant liver tumors and has been well established at many specialized centers. Many different techniques of tissue dissection have been developed. As an alternative various lasers have been applied to conventional liver resections. Laser surgery is potentially beneficial for laparoscopic liver resection, allowing parenchymal dissection and vessel coagulation. A second advantage is the non-ferromagnetic character of this instrument, which facilitates magnetic resonance (MR)-guided interventions. In this study two different Nd:YAG lasers were evaluated for laparoscopic liver resection in a porcine model. In other studies this technique will be transferred into an interventional open MRI for image-guided liver resection. We used 1064-nm and 1318-nm Nd:YAG lasers for laparoscopic wedge, segmental, and left lateral liver lobe resection. During the intervention blood loss, resection time, and cardiopulmonary parameters were quantified. The resected specimen underwent histomorphometric analysis for thermal tissue effects, including parenchymal carbonization, necrosis, and vessel coagulation. The resected volume showed a positive correlation with intraoperative blood loss, which increased from wedge resection (245 mL, SD +/- 71 mL) and segment resection (325 mL), to left lateral resection (455 mL). Total parenchymal dissection was slightly faster with the 1064-nm Nd:YAG laser (9 min, SD +/- 5 min) compared with the 1318-nm Nd:YAG laser (11 min, SD +/- 4 min). Thermally-induced vessel sealing was shown for liver veins and arteries to a maximum diameter of 2 mm. Laparoscopic liver resection with both Nd:YAG lasers is a safe and feasible technique, allowing parenchymal dissection and coagulation. The 1064-nm Nd:YAG laser showed increased tissue damage with more effective coagulation capability than the 1318-nm Nd:YAG laser. Because of its non-ferromagnetic characteristics, laser-based laparoscopic liver resection is potentially useful for image-guided surgery in an open MRI.

Liver lobe torsion in a Shih‐tzu dog

MADAM We write to report a case of liver lobe torsion (LLT) in a small breed dog where ultrasound and computed tomography (CT) were useful in diagnosis of the condition. A 3-year-old male shih-tzu was presented with abdominal pain and acute onset vomiting, followed by progressive weakness. On examination the abdomen was tense and a firm painful mass was palpated cranially. Haematology and biochemistry profiles showed elevated liver enzymes, mild anaemia, and mild thrombocytosis. Abdominal radiographs showed a triangular mass in the cranial abdomen to the left of midline and caudal to the liver displacing the small intestine and the left kidney caudally. An abdominal ultrasound revealed a small volume of anechoic peritoneal effusion and an enlarged, homogenous, and hypoechoic left liver lobe. No blood flow was seen in the vessels including the hepatic veins and the portal veins within this liver lobe. Four detector-row CT was performed without anaesthesia. Pre-contrast CT revealed enlargement and caudoventral deviation of the left liver lobe with an irregular surface. Hypodense free fluid was present in the peritoneum. Post-contrast images showed no change in density of the abdominal left liver but normal contrast enhancement was seen in the remainder of the hepatic parenchyma (Figs 1A and 1B). A dorsal-plane image showed fissures on the liver surface, supporting rupture of the liver (Fig 1C, arrows). A diagnosis of LLT was made based on the imaging findings. Pre-contrast (A) and post-contrast (B,C) CT images through the cranial abdomen reveal an enlargement of the left lateral (LL) and left medial (LM) liver lobe without contrast enhancement. On dorsal-plane image, there are fissures on the liver surface (arrows) After a transfusion of whole blood, an exploratory laparotomy was performed. At surgery, 180 degree torsion of the left medial and left lateral liver lobe was identified and haemorrhagic peritoneal effusion and parenchymal rupture were present. A lobectomy of the affected regions was performed. The patient awoke from the anaesthesia, but died six hours after surgery. The cause of death was suspected to be severe postoperative complications. Most previous reports of LLT in dogs occurred in large breeds (Swann and Brown 2001, Schwartz and others 2006) and a few medium-sized breeds including the beagle (Sonnenfield and others 2001). To the author’s knowledge, this is the first case reported in such a small breed dog. Furthermore, this is the first report of the use of CT in diagnosis of the condition. Multiplanar reconstructions are particularly useful in assessment of complex anatomical abnormalities such as lung lobe torsion, and in this case, LLT. Liver lobe torsion, though very rare, should be considered in the differential diagnosis for acute abdominal pain, even in small breed dogs.

Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone

Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy. Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively. In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls. The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning.

Left Lateral and Left Middle Liver Lobe Torsion in a Saint Bernard Puppy

A 5-month-old, male Saint Bernard was presented for acute collapse and abdominal discomfort. Significant findings were a cranial abdominal mass, hemorrhagic abdominal effusion, anemia, and disseminated intravascular coagulation. An exploratory surgery revealed torsion of both the left lateral and middle liver lobes, a condition that has not been previously described in the veterinary literature. Torsion of one or more hepatic lobes is a rare condition but should be considered as a differential diagnosis for acute abdomen syndrome in both young and mature dogs. Early diagnosis and prompt surgical intervention may be curative.

Atrophy-Hypertrophy Complex in Patients with Cavernous Transformation of the Portal Vein: CT Evaluation

To retrospectively evaluate the morphologic changes in the liver associated with cavernous transformation of the portal vein. This study was institutional review board approved. Informed patient consent was not required. The computed tomographic (CT) results for 22 patients (14 male, eight female; mean age, 54 years) with cavernous transformation of the portal vein and no evidence of chronic liver disease at liver biopsy were retrospectively reviewed and compared with the CT results for 36 control subjects. Various morphologic changes in the hepatic lobes were qualitatively and quantitatively assessed by using the Student t test for unpaired data. Qualitative analysis revealed the atrophy-hypertrophy complex in most (n = 20, 91%) of the patients with cavernous transformation and in no control subjects. Atrophy of the left lateral segment and right liver lobe was seen in 16 (73%) and seven (32%) patients, respectively. Hypertrophy of the caudate lobe and liver segment IV was identified in 19 (86%) and 11 (50%) patients, respectively. All mean caudate lobe volume index values and mean caudate lobe-to-right lobe ratio values were significantly greater (P < .05) in the cavernous transformation group than in the control group. The mean segment IV diameter was significantly greater (41.6 vs 28.1 mm, P < .001) in the patients with cavernous transformation. Hepatic nodules and hepatic contour nodularity were not seen in the patients with cavernous transformation. The atrophy-hypertrophy complex is frequently observed in patients with cavernous transformation of the portal vein. Some findings, such as hypertrophy of the caudate lobe, mimic chronic liver disease or signs of portal hypertension, but left lateral segment atrophy and a normal or enlarged segment IV are distinctive findings of cavernous transformation.

Ischemic Preconditioning Prevents Apoptotic Cell Death and Necrosis in Early and Intermediate Phases of Liver Ischemia-Reperfusion Injury in Rats

Ischemic preconditioning (IPC) may be useful in attenuating the hepatic ischemia reperfusion (IR) syndrome by means of improving cell resistance to anoxia and reoxygenation and preventing cell death. Since there are insufficient data available regarding the chronology of preconditioning effects, we investigated the role of IPC, to test the hypothesis that liver protection would occur during the early and intermediate phases of the reperfusion period. Wistar rats (n = 72) were randomly assigned into six experimental groups, 12 animals each. A 40-min ischemia to the left lateral and median liver lobes was induced by selective hepatic pedicle clamping followed by 30 min or 240 min of reperfusion (IR30 and IR240). IPC groups (IPC30 and IPC240) underwent a 10 min of ischemia followed by 10 min of reperfusion preceding the definitive 40-min ischemic period. Sham-operated animals were followed for 30 and 240 min. Hepatic enzymes and histological evaluation were performed after the reperfusion period. Hepatic ischemia–reperfusion (IR30 and IR240) induced marked increases in liver enzymes levels after 30 min and particularly after 240 min. IPC effectively attenuated those enzymatic increases. Microvesicular steatosis was observed after 30 min, but not 240 min, of reperfusion in both IPC and IR livers. Necrosis was detected in 66.7% of IR240 and only in 8.3% of IPC240. Both hepatocyte and sinusoidal apoptosis were markedly attenuated by IPC. We conclude that IPC provided protection against hepatic ischemia reperfusion injury in early and intermediate phases of the reperfusion period, reducing hepatic enzymatic leakage and ameliorating hepatic apoptosis and necrosis.

Evaluation of Hemorrhage, Sample Size, and Collateral Damage for Five Hepatic Biopsy Methods in Dogs

To compare the volume of hemorrhage, number of lobules, and portal triads available for histologic evaluation, and resultant collateral damage between 5 hepatic biopsy methods: biopsy punch, biopsy needle, ligature method, laparoscopic biopsy forceps, and ultrasonically activated scalpel (UAS). Experimental, repeated measures, block. Twelve adult dogs. Biopsies were obtained from the periphery and center of the left lateral liver lobe of each dog using each of 5 biopsy techniques. Hemorrhage was quantified and compared between methods and sites. Biopsy samples were evaluated histologically to characterize collateral damage and determine the number of lobules and portal triads sampled. Regardless of technique, liver biopsy resulted in minimal hemorrhage (<2 mL). For peripheral biopsies, UAS was comparable with the ligature method, but caused significantly less hemorrhage than all other methods, whereas for central biopsies, UAS caused significantly less hemorrhage than other methods. Except for the laparoscopic biopsy forceps, UAS caused significantly more collateral damage than other methods. UAS and ligature biopsy methods yielded specimens that had more portal triads per sample than other methods. Eight of 48 biopsy needle samples were inadequate for histologic evaluation, whereas other methods yielded adequate specimens. All biopsy methods produced minimal hemorrhage and except for needle biopsy yielded adequate tissue samples for histologic evaluation. Use of UAS is a reliable, safe alternative technique for liver biopsy and can be used laparoscopically to obtain large tissue samples.

Improvement of postischemic hepatic microcirculation after endothelinA receptor blockade—endothelin antagonism influences platelet-endothelium interactions

Endothelin (ET) contributes to disturbances of hepatic microcirculation after ischemia/reperfusion (I/R) by causing vasoconstriction and enhancing leukocyte- and platelet-endothelium interactions. The aim of this study was to investigate a possible protective role of a selective endothelin(A) receptor antagonist (ET(A)-RA) in this setting. In a rat model, warm ischemia of the left lateral liver lobe was induced for 90 minutes under intraperitoneal anesthesia with xylazine and ketamine. Groups of rats consisted of sham-operated (SO, n=14), untreated ischemia (n=14), and treatment with BSF208075 (5 mg/kg body weight IV, n=14). The effect of the ET(A)-RA on I/R was assessed by in vivo microscopy 20 to 90 minutes after reperfusion; by measurement of local tissue Po(2), serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutathione S-transferase alpha levels, and by histologic investigation. In the untreated group, sinusoidal constriction to 69.4+/-6.7% of diameters of SO rats was observed, leading to a significant decrease in perfusion rate (74.3+/-2.1% of SO) and liver tissue Po(2) (43.5+/-3.2% of SO) (P < 0.05). In addition, we found an increased percentage of stagnant leukocytes (142.9+/-11.9%) and platelets (450.1+/-62.3%) in sinusoids and in postsinusoidal venules (P < 0.05). Hepatocellular damage (AST and ALT increase to 1330+/-157 U/L and 750+/-125 U/L respectively; previously, 27.1+/-3.5 U/L and 28.5+/-3.6 U/L) was detected 6 hours after reperfusion (P < 0.05). Administration of the ET(A)-RA before reperfusion significantly reduced I/R injury. Sinusoidal diameters were maintained (108.5+/-6.6%), and perfusion rate (93.1+/-1.8%) and tissue Po(2) (95.3+/-5.7%) were significantly increased (P < 0.05). According to reduced leukocyte-endothelium interactions after therapy, both platelet rolling and adhesion were significantly reduced (P < 0.05). The number of stagnant platelets in sinusoids was 199.5+/-12.3% of 50 (P < 0.05). After treatment, hepatocellular damage was decreased (AST and ALT levels after 6 hours of reperfusion: 513+/-106 U/L and 309+/-84 U/L, respectively; P < 0.05), and histologic changes were reduced in the long term. Our results provide evidence that the new therapeutic approach with an ET(A)-RA is effective in reducing hepatic I/R injury. In addition to reduced leukocyte-endothelium interactions, the number of stagnant and rolling platelets in sinusoids and venules was significantly reduced. The reduction in microcirculatory damages is responsible for better organ outcome.

Bile duct exclusion from selective vascular inflow occlusion in rat liver: Role of ischemic preconditioning and N-acetylcysteine on hepatic reperfusion injury

Aim To study the effects of N-acetylcysteine and ischemic preconditioning on the portal triad clamping compared to arterial and portal clamping alone. Methods Eighty EPM 1-Wistar rats were randomized into two groups, depending on inclusion (Group 1) or not (Group 2) of the bile duct in the hepatic vascular pedicle occlusion. Each group was divided into four subgroups as follows. IR 1: 20 minutes after celiotomy, the pedicle containing vascular elements and bile duct to the left lateral and median liver lobes was occluded for 40 minutes, followed by 30 minutes of reperfusion. IPC 1: after 10 minutes of ischemia and 10 minutes of reperfusion, the ischemic preconditioning period, the rats were submitted to the same procedure described for IR 1 Group. NAC 1: the rats received N-acetylcysteine (150 mg/kg) 15 minutes before 40 minutes of ischemia and 5 minutes before 30 minutes of reperfusion. SHAM 1: The hepatic pedicle for the lateral and median liver lobes was dissected after 20 minutes, the bile duct alone was clamped for 40 minutes, and released for an additional 30 minutes. In the IR 2, IPC 2, and NAC 2 groups, ischemia was achieved with an exclusive vascular occlusion. SHAM 2: dissection and observation for 90 minutes. The blood was sampled for liver enzyme levels. Statistical analysis was done ( P ≤ .05). Results Hepatic IR injury was less severe for animals from the classic portal triad clamping (group 1), with regard to AST (IR 1 Group 766 vs IR 2 Group 1380 U/L) and ALT (IR 1 Group 840 vs IR 2 Group 1576 U/L); IPC, but not NAC administration, was able to protect the liver from IR injury for animals from the classic portal triad clamping group, with regard to AST (IPC 1 Group 421 vs NAC 1 Group 1131 U/L) and ALT (IPC 1 Group 315 vs NAC 1 Group 1085 U/L). Conclusions IPC protects the liver from IR injury; classic portal triad clamping results in a less severe hepatic IR injury when compared to bile duct exclusion.

Preoperative hepatic venous embolization for partial hepatectomy combined with segmental resection of major hepatic vein.

Liver resection of segments VII and/or VIII sometimes requires segmental resection of the right hepatic vein in patients with liver tumours invading or located close to the hepatic vein. In this situation, hepatic vein reconstruction is thought to have an important role in the postoperative function of segment VI. This study investigated whether preoperative embolization of the major hepatic vein could obviate the need for hepatic vein reconstruction after cranial partial resection of the liver including the major hepatic vein trunk in a preclinical model. Sixteen beagles were divided into two groups of eight: control group (hepatectomy alone) and hepatic venous embolization (HVE) group (hepatectomy after HVE). HVE was performed 2 weeks before hepatectomy. All dogs underwent resection of the cranial third of the left lateral liver lobe together with the major trunk of the left hepatic vein. Following hepatectomy, survival, histological features, portal venous pressure and serum aspartate aminotransferase (AST) levels were determined. Six control animals and seven in the HVE group were alive 1 week after hepatectomy. Immediately after hepatectomy, portal venous pressure was significantly higher in the control group compared with the HVE group (mean(s.d.) 14.0(1.1) versus 8.1(1.0) mmHg; P < 0.01). Histological examination of the remnant left lateral lobe demonstrated patchy parenchymal haemorrhage in the control group and normal parenchymal architecture in the HVE group. Peak AST levels were observed on day 1 in both groups and were significantly higher in the control group (mean(s.d.) 182(42) versus 67(40) units/l; P < 0.01). In this model, preoperative HVE facilitated interlobar venous collateral formation and minimized the untoward effects of segmental hepatic vein resection. This procedure may obviate the need for hepatic vein reconstruction after cranial partial liver resection including the major hepatic vein.

Portal Vein Embolization vs. Portal Vein Ligation for Induction of Hypertrophy of the Future Liver Remnant

The objective of this study was to assess the efficacy of right portal vein embolization (PVE) vs. right portal vein ligation (PVL) for induction of hypertrophy of the left lateral liver lobe before extended right hepatectomy. Thirty-four patients with primary or secondary liver tumors and estimated remnant functional liver parenchyma of less than 0.5% of body weight underwent either right PVE (transcutaneous, n = 10; transileocolic, n = 7) or right PVL (n = 17). Liver volume was assessed by CT scan before occlusion of the right portal vein and prior to resection. There were no deaths. The morbidity rate in each group was 5.8% (PVE, 1 abscess; PVL, 1 bile leak). The increase in liver volume was significantly higher after PVE compared with PVL (188 ± 81 ml vs. 123 ± 58 ml) ( P = 0.012). Postoperative hospital stay was significantly shorter after PVE in comparison to PVL (4 ± 2.9 days vs. 8.1 ± 5.1 days; P < 0.01). Curative liver resection was performed in 10 of 17 patients after PVE and 11 of 17 patients after PVL. PVE and PVL were found to be feasible and safe methods of increasing the remnant functional liver volume and achieving resectability for extended liver tumors. PVE results in a significantly more efficient increase in liver volume and a shorter hospital stay. (J G astrointest S urg 2002;6:905–913)

Microwave coagulation therapy accelerates growth of cancer in rat liver

Background/Aims: Although microwave coagulation therapy (MCT) has been performed for liver cancer, there has been no report examining the influence of this therapy on the growth of possible remnant cancer. Methods: A solid cube of AH-130 cells (ascites hepatoma cell line) was implanted into the left lateral lobe of the rat liver. Five days later, MCT was applied to the middle liver lobe of these rats. Tumor growth and cytokine levels in plasma and the liver were compared between rats that underwent MCT and rats that did not. Results: The mean tumor weight in the MCT group (222.6±51.5 mg, mean±SD) was significantly greater than that in the control group (126.7±19.7 mg, P<0.01) at postoperative day (POD) 5. Immunohistochemistry for anti-proliferating cell nuclear antigen showed the labeling index in the MCT group (90.4%) to be higher than that in the control group (76.7%, P<0.01). Liver basic fibroblast growth factor and transforming growth factor-beta 1 levels in the MCT group on POD 3 were significantly higher than levels in the control group. Conclusions: The present study suggests the clinically important finding that MCT accelerates the growth of small residual tumors in the liver.

An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features.

To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization. Forty male Wistar rats were implanted with Walker-256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n=8) and native magnetic resonance (MR, n=40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings. Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocarcinoma in growth pattern and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9+/-48.7 mm(3). No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6+/-214.8 mm(3) in the control group and 356.5+/-78.4mm(3) in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21. Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.

Endotoxin tolerance protects against local hepatic ischemia/reperfusion injury in the rat

Liver surgery and liver transplantation as well as circulatory shock are often associated with hepatic ischemia/reperfusion (I/R) injury. Recent evidence suggests that TNF-α plays a central role in I/R injury and, therefore, down-regulation of TNF-α seems to be a promising way to protect against the deleterious consequences of I/R. Endotoxin tolerance represents a state of unresponsiveness to endotoxin and is associated with diminished TNF-α production. Thus, the effect of endotoxin tolerance on hepatic I/R injury of the liver was investigated in a rat model. I/R injury was induced by temporary ischemia of the left lateral liver lobe for 90 min followed by a 3 h observation period of reperfusion. I/R injury resulted in functional hepatic disorder characterized by a decrease both in bile flow and bile acid concentration and 50% mortality. This was prevented by induction of endotoxin tolerance. Hepatic TNF-α mRNA expression after I/R of the liver was determined by RT-PCR. In untreated rats, TNF-α mRNA was induced in the liver 60 min after reperfusion and further increased until 3 h after reperfusion. In contrast, in endotoxin-tolerant rats, no increases in TNF-α mRNA expression were detected. This suggests that induction of endotoxin tolerance protects against hepatic I/R injury possibly via down-regulation of intra-organ TNF-α expression.

Endotoxin tolerance protects against local hepatic ischemia/reperfusion injury in the rat.

Liver surgery and liver transplantation as well as circulatory shock are often associated with hepatic ischemia/reperfusion (I/R) injury. Recent evidence suggests that TNF-alpha plays a central role in I/R injury and, therefore, down-regulation of TNF-alpha seems to be a promising way to protect against the deleterious consequences of I/R. Endotoxin tolerance represents a state of unresponsiveness to endotoxin and is associated with diminished TNF-alpha production. Thus, the effect of endotoxin tolerance on hepatic I/R injury of the liver was investigated in a rat model. I/R injury was induced by temporary ischemia of the left lateral liver lobe for 90 min followed by a 3 h observation period of reperfusion. I/R injury resulted in functional hepatic disorder characterized by a decrease both in bile flow and bile acid concentration and 50% mortality. This was prevented by induction of endotoxin tolerance. Hepatic TNF-alpha mRNA expression after I/R of the liver was determined by RT-PCR. In untreated rats, TNF-alpha mRNA was induced in the liver 60 min after reperfusion and further increased until 3 h after reperfusion. In contrast, in endotoxin-tolerant rats, no increases in TNF-alpha mRNA expression were detected. This suggests that induction of endotoxin tolerance protects against hepatic I/R injury possibly via down-regulation of intra-organ TNF-alpha expression.

Effects of ischaemia and reperfusion on NADH coenzyme Q reductase activity in rat liver.

NADH coenzyme Q reductase (EC 1.6.5.3) has been suggested in the literature to be inactivated by ischaemia. In the present study, NADH coenzyme Q reductase activity was localized in unfixed cryostat sections of ischaemic rat livers and quantified using image analysis. In vitro ischaemia was induced by storage of rat liver fragments for 30, 60, and 120 min at 37 degrees C. In vivo ischaemia was provoked by clamping the afferent vessels of median and left lateral liver lobes for 60 min followed by 30, 60 and 180 min of reperfusion. NADH coenzyme Q reductase activity was demonstrated with the tetrazolium salt method in the presence of polyvinyl alcohol. Final reaction product was found in liver parenchymal cells and its distribution was homogeneous within liver lobules. Only low amounts of final reaction product were formed when the incubation was performed in the absence of the substrate NADH. A non-linear relation was found between the absorbance and incubation time when the reaction was performed in the presence of NADH. Therefore, the initial velocity was taken as the true rate of enzyme activity. A linear relationship was found for the initial velocity and section thickness up to 6 microm followed by a levelling off. Electron microscopically, NADH coenzyme Q reductase activity was localized at the outer and inner membranes of mitochondria. In vitro ischaemia up to 120 min did not affect NADH coenzyme Q reductase activity. At 30 min reperfusion after in vivo ischaemia for 60 min enzyme activity was slightly decreased in certain foci which also showed diminished lactate dehydrogenase activity. A further decrease of enzyme activities in foci was observed at 180 min reperfusion after ischaemia. It is concluded that NADH coenzyme Q reductase activity is not sensitive to ischaemia. Furthermore, it is likely that the enzyme leaks from liver parenchymal cells into the circulation during reperfusion after ischaemia.