Left Lateral Hepatic Lobe Research Articles

Orthotopic Model of Hepatocellular Carcinoma in Mice.

Orthotopic models of hepatocellular carcinoma (HCC) consist in the implantation of tumor cells into the liver by direct intrahepatic injection. In this model, tumorigenesis is triggered within the hepatic microenvironment, thus mimicking the metastatic behavior of HCC. Herein, we detail a surgically mediated methodology that allows the reproducible and effective induction of liver-sessile tumors in mice. We enumerate the steps to be followed before and after the surgical procedure, including HCC cell preparation, the quantity of cancer cells to be injected, presurgical preparation of the mice, and finally, postoperative care. The surgical procedure involves laparotomy to expose the liver, injection of cells into the left-lateral hepatic lobe, and closure of the incision with sutures followed by wound clips. We also provide information concerning the subsequent tumor growth follow-up, as well as the application of bioluminescence imaging to monitor tumor development.

Long‐term survival of a dog diagnosed with a primary multicentric hepatic plasma cell tumour treated with surgery and chemotherapy

AbstractA 7‐year‐old, intact, female Jack Russell terrier was presented for evaluation of a mammary nodule. Abdominal ultrasonography for initial staging revealed a 1 cm hypoechoic nodule within the left lateral hepatic lobe (LLHL), which was histologically determined to be a plasma cell tumour (PCT). Computed tomography revealed an additional 5 mm nodule in the right medial hepatic lobe (RMHL). Exploratory celiotomy showed that the PCT in the LLHL adhered to the gastric wall. Partial liver lobectomy and partial gastrectomy were carried out to remove the PCT in the LLHL. Marginal excision was done to remove the RMHL nodule, which was determined to be a PCT. The dog was treated with prednisone and melphalan for 6 months and remained in complete clinical remission for 37 months. Surgery and adjuvant chemotherapy were successful in maintaining long‐term remission in this patient. This is the first report of primary multicentric hepatic PCT in a dog.

An unusual presentation of a hepatic ductal malformation in a Boxer dog

AbstractAn 11‐year‐old male neutered Boxer presented for evaluation of an external ear canal mass, postoperatively diagnosed as a benign inflammatory lesion. Preoperative staging of the ear mass identified a 10‐cm mass affecting the majority of the left lateral hepatic lobe, with inconclusive cytology. A left lateral liver lobectomy was performed. Histopathology revealed the hepatic parenchyma was largely effaced and replaced by a myriad of small calibre tubules lined by well‐differentiated biliary epithelium (cytokeratin19 and cytokeratin7 positive (CK19+, CK7+) supported by abundant fibrosis. Small cords and islands of hepatocytes (hepatocyte paraffin1 positive) (HepPar1+) were entrapped throughout these bile ducts. Analysis of the proliferation index via antigen KI‐67 (Ki67) immunohistochemistry confirmed lack of proliferative activity. Histological and immunohistochemical features were consistent with a ductal plate malformation (DPM). This is the first time a DPM of this size has been described on a computed tomography (CT) scan.

Sample strategies for quantification of hepatic fat fraction mean MRI in healthy cats during body weight gain.

Hepatic fat fraction (HFF) can be non-invasively estimated with magnetic resonance imaging (MRI) multiple echo gradient recalled echo (GRE) sequence. The aim of this study was to test different methods of sampling strategies to quantify the HFF in healthy cats during body weight gain. Twelve healthy adult male cats were examined in a 3 Tesla MRI unit. Sequences included morphological images, and multiple echo GRE sequence. Cats were scanned at the beginning of the study and twice, each 20 weeks apart during body weight gain. HFF was calculated with 5 different methods of sampling on the multiple echo GRE sequence with different number, size and position of regions of interest (ROIs) and by 2 operators. Results indicated that HFF increased with increasing body weight, and the increase was appreciated with all the 5 methods. There was overall excellent agreement (interclass correlation coefficient = 0.820 (95% confidence interval:0.775–0.856)) between the 2 operators. HFF in the left lateral hepatic lobe was lower than in the other analyzed lobes. HFF measured on large free-hand drawn ROIs was higher than HFF measured with smaller ROIs size. This study proves that different sampling methods for quantification of HFF on multiple echo GRE sequence have overall excellent repeatability and ability to appreciate increased HFF.

P 037 - Effect of Neutral Sphingomyelinase Inhibition on ER Stress and Apoptosis in Liver Ischemia–Reperfusion Injury

This study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on endoplasmic reticulum (ER) stress and apoptotic markers in a rat model of liver ischemia reperfusion (IR) injury. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Sphingmyelin and ceramide levels in liver tissue were determined by tandem mass spectrometry. Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. A significant increase was observed in ER stress markers C/EBP-homologous protein (CHOP) and 78 kDa glucose-regulated protein (GRP78) in IR injury, which was not significantly altered by N-SMase inhibition. Inhibition of N-SMase caused a significant reduction in phospho-NF-kB levels, hepatic TUNEL staining, cytosolic cytochrome c and caspase-3, -8 and -9 activities which were significantly increased in IR injury. Data herein confirm the role of ceramide in increased apoptotic cell death and highlight the protective effect of N-SMase inhibition in down-regulation of apoptotic stimuli responses occurring in hepatic IR injury.

Ozone oxidative intervention protects against hepatic ischemia reperfusion injury in rats

Objective To explore the protective effect of ozone oxidative preconditioning on hepatic ischemia reperfusion injury in rats. Methods Eighteen 8-week-old SPF Sprague-Dawley male rats weighting 250~300 g were randomly divided into three groups (n=6 each): sham operation group (group S), ischemia/reperfusion group (group I/R) and ozone oxidative preconditioning group (group O3+ I/R). In Group O3+ I/R, rats received five-day preconditioning treatments by intraperitoneal injection of ozone and oxygen mixed gases (ozone concentration 50 mg/L, 1 mg·kg-1·d-1), and then experienced the procedure of hepatic ischemia/reperfusion injury. Model of hepatic ischemia/reperfusion injury was established by clamping the branches of hepatic artery and portal vein in the median and left lateral hepatic lobes for 45 min, followed by 3-h reperfusion. After reperfusion, blood samples were taken from the aorta abdominalis for detecting serum aminotransferases (ALT & AST). These rats were executed and the hepatic tissue samples were collec-ted for measuring hepatic malondialdehyde (MDA) and superoxide dismutase (SOD) level. Results Compared with group S, concentrations of serum ALT, AST and hepatic MDA were increased in group I/R and O3+ I/R; concentrations of hepatic SOD were decreased (P<0.05) in group I/R, but concentration of hepatic SOD was increased in group O3+ I/R. Compared with group IR, concentrations of serum ALT, AST and hepatic MDA were decreased, while concentration of hepatic SOD was increased in group O3+ I/R (P<0.05). Conclusion Ozone oxidative preconditioning could inhibit the lipid peroxidation to protect the rats against hepatic ischemia/reperfusion injury. Key words: Ozone oxidative preconditioning; Ischemia/reperfusion injury; Liver

Neutral sphingomyelinase inhibition alleviates apoptosis, but not ER stress, in liver ischemia–reperfusion injury

Previous studies have revealed the activation of neutral sphingomyelinase (N-SMase)/ceramide pathway in hepatic tissue following warm liver ischemia reperfusion (IR) injury. Excessive ceramide accumulation is known to potentiate apoptotic stimuli and a link between apoptosis and endoplasmic reticulum (ER) stress has been established in hepatic IR injury. Thus, this study determined the role of selective N-SMase inhibition on ER stress and apoptotic markers in a rat model of liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reactions monitoring (MRM) method using ultrafast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared with controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. A significant increase was observed in ER stress markers C/EBP-homologous protein (CHOP) and 78 kDa glucose-regulated protein (GRP78) in IR injury, which was not significantly altered by N-SMase inhibition. Inhibition of N-SMase caused a significant reduction in phospho-NF-kB levels, hepatic TUNEL staining, cytosolic cytochrome c, and caspase-3, -8, and -9 activities which were significantly increased in IR injury. Data herein confirm the role of ceramide in increased apoptotic cell death and highlight the protective effect of N-SMase inhibition in down-regulation of apoptotic stimuli responses occurring in hepatic IR injury.

Immune and Inflammatory Responses of the Intestinal Mucosa following Extended Liver Radiofrequency Ablation.

Background and Aim Extended liver radiofrequency ablation (RFA) has been shown to disrupt gut barrier integrity with subsequent bacterial translocation. The aim of the present project was to study the immune and inflammatory responses of the intestinal mucosa after extended RFA of the liver. Methods Twelve Wistar rats were either subjected to RFA of the left lateral hepatic lobe (approximately 30% of the liver mass) after midline laparotomy (group RFA, n = 6) or sham operation (group Sham, n = 6). Forty-eight hours later, ileal tissue specimens were excised for immunohistochemical assessment of CD68+ macrophages, CD4+ T-lymphocytes, CD8+ T-lymphocytes, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and nuclear factor-κB (NFκB) expression. Results Immune response biomarkers were upregulated in the RFA group. Expression of CD4+ and CD8+ T-lymphocytes was moderate, while that of CD68+ macrophages and MAdCAM-1 was high. Inflammatory response biomarkers were also upregulated in the RFA group. TNFα, IL-6, and NFκB expression was low, moderate, and high, respectively. Conclusions Extended liver RFA evokes both immune and inflammatory responses of the gut mucosa.

A laparoscopic technique of partial hepatectomy in the rat

BackgroundLaparoscopic partial hepatectomy is an increasingly applied technique in the treatment of liver tumors and in living donor transplantation. There is a need for establishing an animal model that would facilitate experimental research on the technique. The aim of the present study was to describe a safe and efficient laparoscopic technique of 70% partial hepatectomy in the rat. Materials and methodsTwenty-four male Wistar rats underwent either laparoscopic (group LAP-HEP) or open resection of the median and left lateral hepatic lobes (group HEP). In group LAP-HEP, a 5-mm Hg pneumoperitoneum was established. Three 5-mm trocars were introduced in the abdominal cavity. A self-made pretied ligature loop was used to ligate en bloc the pedicles of the hepatic lobes to be resected. A self-made sterile elastic specimen retrieval bag facilitated extraction of the resected liver tissue. In group HEP, the same liver lobes were resected by ligation of their pedicles after midline laparotomy. ResultsThe percentage of resected liver parenchyma did not differ between groups. All animals returned to normal feeding activity by 48 h postoperation and had no complications. ConclusionsA simple, cost-effective, safe, and efficient laparoscopic technique for 70% partial hepatectomy in the rat was described.

Inhibition of neutral sphingomyelinase decreases elevated levels of nitrative and oxidative stress markers in liver ischemia–reperfusion injury

Oxidative stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS)-2 have been shown in the pathogenesis of liver ischemia–reperfusion (IR) injury. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression therefore this study determined the role of selective N-SMase inhibition on nitrative and oxidative stress markers following liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Nitrative and oxidative stress markers were determined by evaluating NOS2 expression, protein nitration, nitrite/nitrate levels, 4-hydroxynonenal (HNE) formation, protein carbonyl levels and xanthine oxidase/xanthine dehydrogenase (XO/XDH) activity. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reaction monitoring method using ultra-fast liquid chromatography coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. NOS2 expression, nitrite/nitrate levels and protein nitration were significantly greater in IR injury and decreased with N-SMase inhibition. Treatment with a selective N-SMase inhibitor significantly decreased HNE formation, protein carbonyl levels and the hepatic conversion of XO. Data confirm the role of nitrative and oxidative injury in IR and highlight the protective effect of selective N-SMase inhibition. Future studies evaluating agents blocking N-SMase activity can facilitate the development of treatment strategies to alleviate oxidative injury in liver I/R injury.

3:45 PMAbstract No. 44 - Thermal ablation induces accelerated intrahepatic tumor growth in an orthotopic model of hepatocellular carcinoma

Previous clinical studies have shown that aggressive intrahepatic recurrence may occur following thermal ablation of HCC. However, there are currently no experimental models for studying thermal ablation-induced accelerated intrahepatic tumor growth. The aim of the present study was to test the hypothesis that liver thermal ablation induces accelerated local versus distant intrahepatic tumor growth in an orthotopic model of hepatocellular carcinoma. In an IACUC-approved study, 3x106 N1S1 rat HCC cells were inoculated into the median hepatic lobe of Sprague-Dawley rats. The tumor-cell bearing rats were randomized to immediate laser thermal ablation of the median hepatic lobe (local intrahepatic group) at 3W x 60s (N=6), 3W x 90s (N=6) or sham laser ablation (N=7). The experiment was repeated with inoculation of N1S1 cells into the median hepatic lobe and laser thermal ablation of the left lateral hepatic lobe (distant intrahepatic group) at 3W x 90s (N=7) or sham laser ablation (N=7). Tumor growth was monitored by T2-weighted magnetic resonance imaging (MRI) at 4, 10, 14 and 18 days post-ablation. Tumor volumes calculated from MR images were compared by ablation dose (sham v. 60s v. 90s) and intrahepatic tumor site (local v. distant). Thermal liver ablation induced accelerated growth of local intraheptatic tumor compared to sham ablation by day 18 in a dose dependent manner (1363mm3±361v. 3102 mm3±463 v. 3538mm3±667; sham v. 60s v. 90s; p<0.05; p<0.01). Thermal liver ablation did not induce accelerated growth of distant intrahepatic tumor compared to sham (2023mm3±666 v. 3256 mm3±632; p=0.2). These data suggest that thermal ablation of liver induces accelerated growth of intrahepatic tumor in a thermal-dose dependent manner. Moreover, local intrahepatic growth mechanisms may play a greater role than systemic growth mechanisms in ablation-induced accelerated tumor growth in the liver. Further pre-clinical studies in this model may help to identify critical growth factors as candidate therapeutic targets to prevent thermal-ablation induced accelerated tumor growth.

Synchronous double primary malignancies of the liver and kidney: A case report.

A 42-year-old male patient was admitted to the Department of General Surgery of The First Affiliated Hospital of Henan University of Science and Technology (Luoyang, China) presenting with abdominal discomfort. Enhanced computed tomography of the abdomen revealed a 15.1×7.0-cm, enhanced, double-spherical, exogenous, solid tumor originating from the left lateral hepatic lobe, in addition to a 4.3×4.2-cm mass in the mid portion of the left kidney. Pre-operative imaging analysis resulted in the diagnosis of double cancer, consisting of hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The patient subsequently underwent left hemihepatectomy and left nephrectomy. Histological examination confirmed that the tumor originating from the left lateral hepatic lobe was HCC, and the tumor arising from the mid portion of the left kidney was clear cell RCC (ccRCC). The post-operative follow-up was uneventful. To the best of our knowledge, the present case is the first of its kind to describe the resection of synchronous double cancer, consisting of primary HCC and ccRCC.

Analysis of polyunsaturated fatty acids and the omega-6 inflammatory pathway in hepatic ischemia/re-perfusion injury.

The aim of the present study was to assess omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) in liver tissue and evaluate changes in the n-6-associated inflammatory pathway following liver ischemia/re-perfusion (IR) injury. Male Wistar rats which were allowed free access to standard rat chow were included in the study. Blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min of re-perfusion. Levels of arachidonic acid (AA, C20:4n-6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in liver tissue were determined by an optimized multiple reaction monitoring method using ultra fast-liquid chromatography coupled with tandem mass spectrometry. Phospholipase A2 (PLA2), cyclooxygenase (COX) and prostaglandin E2 (PGE2) were measured in tissue samples to evaluate changes in the n-6 inflammatory pathway. Total histopathological score of cellular damage were significantly increased following hepatic IR injury. n-3 and n-6 PUFA levels were significantly increased in post-ischemic liver tissue compared to those in non-ischemic controls. No significant difference was observed in the AA/DHA and AA/EPA ratio in post-ischemic liver tissues compared with that in the control. Tissue activity of PLA2 and COX as well as PGE2 levels were significantly increased in post-ischemic liver tissues compared to those in non-ischemic controls. The results of the present study suggested that increased hydrolysis of fatty acids via PLA2 triggers the activity of COX and leads to increased PGE2 levels. Future studies evaluating agents which block the formation of eicosanoids derived from n-6 PUFAs may facilitate the development and application of treatment strategies in liver injury following IR.

Remain recipient partial liver during liver transplant after Hassab

BackgroundThe Hassab procedure is the primary method for treating and preventing recurrent esophagogastric variceal bleeding in portal hypertension patients. These patients have worsening liver function and eventually require liver transplantation. Abnormal anatomical structures and severe tissue adhesion caused by the Hassab procedure increase the risks of transplantation. We investigated the safety and efficacy of retaining part of the left lateral hepatic lobe during transplantation. Materials and methodsThis retrospective study evaluated outcomes in 22 patients who underwent the Hassab procedure followed by liver transplantation. The patients were separated into two groups: group A (complete liver resection, n = 14) and group B (incomplete liver resection with left lateral remnant, n = 8). We statistically analyzed pre-, intra-, and post-operative variables in both groups. ResultsPreoperative demographic data showed no significant differences between the groups. Operation time was significantly greater in group A (10.85 ± 0.79 h) than in group B (7.25 ± 0.59 h), and median blood loss (2807 ± 472 mL) was significantly greater in group A than in group B (1023 ± 141 mL, P < 0.05 for both). Overall complication rates were not significantly different; the 1- and 3-y survival rates were 85.7% and 71.4% for group A and 87.5% and 75.0% for group B, respectively (P > 0.05). ConclusionsRetention of some left hepatic lobe tissue during liver transplantation after the Hassab procedure is safe and feasible because it increases the success rate by reducing surgical difficulty and time.

Open surgery for liver hydatid disease

Hydatid cyst disease is a cosmopolitan parasitosis. E. granulosis species prevails in most countries around the world and especially in the Mediterranean region. We performed a retrospective literature search on liver hydatid cysts was carried out in ScienceDirect, Scopus, Web of Knowledge, InCites, and MEDLINE data-bases for the period 2000-2012. According to recent literature data, liver is the most commonly affected organ. The principles of surgical approach to the liver hydatid disease include the following: i) neutralization of the parasite; ii) evacuation of the cyst and removal of the germinative layer, and iii) treatment of the remaining cavity. The marsupialization of the remaining cyst is not accepted in case of suppurated hydatid cyst. There are numerous opinions about the most efficient scolicidal solution. The most intractable problem is the approach to the residual cavity of hydatid cyst. Major postoperative complications reported by different authors are mainly inflammatory processes. The radical surgical method is indicated in case of peripherally located hydatid cysts, several cysts grouped in a liver segment or lobe, and cysts located in the left lateral hepatic lobe. The surgical method still remains the golden standard for treatment of liver hydatid cysts. Scripta Scientifica Medica 2013; 45(3): 23-26.

Adrenocortical Carcinoma in a Dog with Incomplete Excision Managed Long-term with Metastasectomy Alone

A 10 yr old bichon frise presented with a 3 mo history of polyuria, polydipsia, and hind limb weakness. Serum biochemistry revealed persistent hypokalemia. A left adrenal gland mass with right adrenal atrophy was detected ultrasonographically. Basal serum cortisol concentration was at the low end of normal (30 nmol/L; reference range, 30-140 nmol/L) and adrenocorticotropic hormone (ACTH)-stimulated cortisol concentration was low (199 nmol/L; reference range, 220-470 nmol/L). Basal serum 17-α-OH progesterone concentration was also low (0.03 ng/mL; reference range, 0.06-0.30 ng/mL), but the aldosterone concentration 2 hr after the ACTH stimulation was elevated (> 3,000 pmol/L; reference range, 197-2,103 pmol/L). A left adrenalectomy and nephrectomy were performed. Histopathology revealed an adrenocortical zona glomerulosa carcinoma. Surgical excision was considered incomplete; however, clinical signs resolved. Two years later, basal and ACTH-stimulated aldosterone concentrations were elevated. Computed tomography demonstrated a mass effect in the liver. The left lateral and left medial hepatic lobes were removed. Histopathology confirmed metastatic endocrine carcinoma. The patient was stable 1,353 days postsurgically (when this report was prepared). This is the first case report of a metastatic adrenal carcinoma that was successfully managed surgically for > 3 yr.

Measurement of intracellular biomolecular oxidation in liver ischemia–reperfusion injury via immuno-spin trapping

Hepatic ischemia–reperfusion (I/R) can lead to liver failure in association with remote organ damage, both of which have significant rates of morbidity and mortality. In this study, novel spin trapping and histopathological techniques have been used to investigate in vivo free radical formation in a rat model of warm liver I/R injury. 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) was administered to rats via intraperitoneal injection at a single dose of 1.5g of pure DMPO/kg body wt 2h before the initiation of liver ischemia. Blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60min, followed by 60min reperfusion. The effects of DMPO on I/R injury were evaluated by assessing the hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Immunoelectron microscopy was performed to determine the cellular localization of DMPO nitrone adducts. Levels of nitrone adducts were also measured to determine in situ scavenging of protein and DNA radicals. Total histopathological scoring of cellular damage was significantly decreased in hepatic I/R injury after DMPO treatment. DMPO treatment significantly decreased the hepatic conversion of xanthine oxidase and 4-hydroxynonenal formation in I/R injury compared to the untreated I/R group. The distribution of gold-nanoparticle-labeled DMPO nitrone adducts was observed in mitochondria, cytoplasm, and nucleus of hepatocytes. The formation of protein– and DNA–nitrone adducts was increased in DMPO-treated I/R livers compared to DMPO controls, indicating increased in situ protein and DNA radical formation and scavenging by DMPO. These results suggest that DMPO reduces I/R damage via protection against oxidative injury.

Imunossupressão com tacrolimus favorece a regeneração hepática induzida por hepatectomia ampla em ratos

To analyze, during two different moments of liver regeneration, the effect of the immunosuppressant Tacrolimus on the 70% hepatectomy model-induced liver regeneration in adult rats. Forty Wistar adult rats, weighing 510.08 + 11.66 g were randomly divided into two groups, each group divided into two subgroups according to the death day after 70% hepatectomy . According to the group of study, rats received 0.1 mg/kg/day of Tacrolimus or the same volume of saline solution, by gavage. After three days of pre-therapy, all animals were submitted to 70% hepatectomy by resection of median and left lateral hepatic lobes which were weighed for posterior calculation of liver regeneration by Kwon's formula. Twenty four hours or seven days after hepatectomy ten rats of each group were killed; the remaining liver (regenerated) was entirely resected, weighed and sampled for mitotic index on hematoxylin-eosin staining and immunohistochemical assays with PCNA and Ki-67 markers. Data were statistically analyzed by Mann-Whitney or Student "t" tests, with significance level of 5% (p<0.05). Rats receiving tacrolimus showed statistically significant higher levels of liver regeneration when compared to placebo according to Kwon's formula, mitotic index and PCNA marker. Identical trend was found with Ki-67 marker, but without statistical significance. Tacrolimus-based immunossuppression has stimulatory effect on liver regeneration process induced by 70% hepatectomy in adult Wistar rats.

Imunossupressão com tacrolimus favorece a regeneração hepática induzida por hepatectomia extensa em ratos

RACIONAL: A regeneração hepática representa o resultado de respostas fisiológicas que ocorrem após perdas de parênquima, como consequência de agressões tóxico-medicamentosas, infecciosas, traumáticas ou cirúrgicas. OBJETIVO: Avaliar, em dois momentos distintos da regeneração hepática, a influência do tacrolimus sobre o fenômeno da regeneração hepática desencadeada pela ressecção de 70% do parênquima hepático em ratos plenamente desenvolvidos. MÉTODO: Utilizaram-se 40 ratos Wistar com peso médio de 510,08 g ± 11.66 g divididos aleatoriamente em dois grupos de 20 (Estudo e Controle), cada grupo subdividido em dois subgrupos conforme o dia da morte após a hepatectomia (24 horas e 7 dias). De acordo com o grupo os animais receberam por gavagem, diariamente, iniciando três dias antes da hepatectomia e prolongando-se por todo o período de observação, solução aquosa de tacrolimus 0,1 mg/kg/dia ou solução salina no mesmo volume. Após três dias de pré-terapia todos foram submetidos à hepatectomia de 70% pela ressecção dos lobos hepáticos mediano e lateral esquerdo que foram pesados para posterior cálculo da regeneração hepática pela fórmula de Kwon. Vinte e quatro horas ou sete dias após a hepatectomia, 10 animais de cada grupo foram mortos, os fígados remanescentes (regenerados) foram pesados e amostrados para realização de índice mitótico por hematoxilina-eosina e estudo imunoistoquímico com os marcadores PCNA e Ki-67. RESULTADOS: Os animais que receberam tacrolimus mostraram índice maior de regeneração hepática, atingindo significância estatística quando comparado ao subgrupo de animais mantidos com placebo quando analisados pelos parâmetros: fórmula de Kwon, índice mitótico e marcador PCNA. A tendência para o marcador Ki-67 foi idêntica aos outros parâmetros, mas não alcançou significância estatística. CONCLUSÕES: A imunossupressão com tacrolimus possui efeito estimulante no processo de regeneração hepática desencadeado pela hepatectomia 70% em ratos Wistar adultos, plenamente desenvolvidos.

Prevenção de isquemia hepática normotérmica durante perfusão hepática in situ com três diferentes soluções de preservação: análise experimental através de termografia por radiação infravermelha em tempo real

To establish the usefulness of infrared radiation thermography on monitoring in situ liver perfusion with different preservation solutions during liver harvesting. Twenty-four adult male Wistar rats, weighing 385.31 g were randomly divided into four groups of six animals each according to the solution used to perfuse the liver (Euro-Collins® solution--EC group; Custodiol® solution--CUST group; Celsior® solution--CEL group and Ringer-Lactate solution--RL group). Under inhalatory ether anesthesia, animals were submitted to upper transversal laparotomy, exposure of median and left-lateral hepatic lobes, heparin injection (500 UI/Kg) through infrahepatic vena cava, portal vein infusion through 18G catheter of cold (4°C) solution according to the group of study. Infrared images, with respective temperature evaluations from hepatic surface, were picked up in real time by Therma CAM SC500® infrared camera positioned at constant distance from three fixed points of the diaphragmatic surface of median and left lateral lobes at the following moments regarding liver perfusion: immediately after laparotomy; after portal vein cannulation and immediately before solution infusion; at each minute from the beginning of liver perfusion during five minutes. Mean temperatures of each moment were compared intra and intergroups with the difference between means test with normal distribution, with significance level of 5% (p=0.05). There was statistically significant difference of means temperatures between the moment of laparotomy and immediately after cannulation; between this later and after the first minute of perfusion; and between the first and fifth minutes of infusion in all groups of study in a similar way. CEL group showed additional difference between the first and second minutes means temperatures. Intergroup comparison showed Euro-Collins solution with significant less cooling power when compared to all others solutions. It was possible to follow the liver cooling process during preservation solutions perfusion using infrared radiation images. Preservation solutions had similar behaviors, with Celsior® solution showing additional cooling power until the second minute of perfusion. Euro-Collins solution had less cooling power than other solutions studied.