OBJECTIVETo determine the effect of pneumoperitoneum on liver indocyanine green (ICG) metabolism and the hepatic blood flow in normal and cirrhotic rats.

METHODSThirty male Wistar rats were randomized into five groups: normal anaesthesia group, normal laparotomy group, normal pneumoperitoneum group, cirrhosis + anaesthesia group, and cirrhosis + pneumoperitoneum group. Liver cirrhosis was induced in two groups by injecting carbon tetrachloride subcutaneously plus drinking 5% alcohol. ICG clearance tests were performed in all the rats.

RESULTSThe ICG level in the normal laparotomy group (0.662 micro g/ml) was higher than that in the normal anesthesia group (0.645 micro g/ml), but the difference was not significant (P > 0,05). The ICG level in the normal pneumoperitoneum group (0.967 micro g/ml) was significantly higher than that in the normal anesthesia and normal laparotomy groups (P < 0.05). The ICG levels in two cirrhotic groups were significantly higher than those in the other three groups (P < 0.05). The ICG level in the cirrhosis + pneumoperitoneum (1.348 micro g/ml) was significantly higher than that in the cirrhosis + anesthesia group (1.198 micro g/ml) (P < 0.05).

CONCLUSIONSDuring laparoscopic surgery, pneumoperitoneum could decrease the liver ICG clearance rate and the hepatic blood flow, which are of clinical significance in determining the state of liver cirrhotic.

Animals ; Disease Models, Animal ; Indocyanine Green ; metabolism ; Liver Circulation ; Liver Cirrhosis, Experimental ; physiopathology ; Male ; Pneumoperitoneum, Artificial ; Rats ; Rats, Wistar

OBJECTIVETo noninvasively evaluate hepatic functional blood flow, intrahepatic shunt rate and hepatic functional reserve in both normal and cirrhotic liver using D-sorbitol and indocyanine green measured by high performance liquid chromatography (HPLC).

METHODSMale Sprague-Dawley (SD) rats were divided into normal control and cirrhotic group in which the rats were administrated with tetrachloride. Then the isolated perfused liver models were established. The pharmacokinetic indexes of D-sorbitol and indocyanine green (ICG) were measured by the traditional spectrophotometry (SPEC) and HPLC respectively.

RESULTS(1) HPLC showed that ICG contained genuine ICG (ICGg) and ICG degraded products (ICGdp), which had similar spectrum but metabolic kinetics different with the retention time of 8.9 minutes and 24.2 minutes respectively. (2) Hepatic intrinsic metabolic capacity (QINT, I) was (36.57+/-13.03) ml/min in control group and (14.39+/-5.13) ml/min in cirrhotic group (t=7.08, P<0.01). (3) Hepatic functional blood flow (QFUNC) in cirrhotic group declined, compared with that in control group (34.06 ml/min+/-5.12 ml/min vs. 17.54 ml/min+/-7.02 ml/min, t=8.41, P<0.01), while intrahepatic shunt rate (QIHS) increased markedly (9.9%+/-1.4% vs. 47.5%+/-20.9%, t=8.35, P<0.01).

CONCLUSION(1) HPLC method is superior to SPEC in measuring ICG, because it can avoid the disturbance from ICGdp, so that ICG measured by HPLC is valid for QINT, I evaluation. (2) The hepatic clearance of D-sorbitol measurement is a noninvasive and reliable method for evaluating the total blood flow in normal liver, and hepatic functional blood flow and intrahepatic shunt rate in cirrhotic liver. (3) Combining D-sorbitol with indocyanine green measurement is helpful for assessment of liver functional reserve.

Animals ; Carbon Tetrachloride Poisoning ; physiopathology ; Indicators and Reagents ; pharmacokinetics ; Indocyanine Green ; pharmacokinetics ; Liver ; physiopathology ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Sorbitol ; pharmacokinetics

OBJECTIVEThe predictive value of postoperative hepatic function evaluated by liver functional imaging combined with single photon emission computed tomography (SPECT) technique was appraised in the present study.

METHODSTwenty New Zealand white rabbits were divided randomly into two groups, including the Hepatic Fibrosis with Carcinoma Group (FC-Group, n = 10) and the Control Group (C-Group, n = 10). All the rabbits underwent the resection of outer-right lobe of the liver. The whole hepatic function indexes, such as HCI(5), HLI(5) and Ex(15), and the hepatic function remnant indexes, including HCI(5P), HLI(5P) and Ex(15P), were calculated by 99mTc-EHIDA liver imaging.

RESULTSEx(15) of FC-Group was lower than that of C-Group (P < 0.05). HCI(5) and HLI(5) of FC-Group had the trends to increase compared with the C-Group. Ex(15) was positively correlated with ALB, and negatively correlated with TBil and GGT (P < 0.05). HCI(5) had a positive correlation with CHE (P < 0.05), while HLI(5) had a negative correlation with A/G (P < 0.05). HLI(5P) had the negative correlation with postoperative A/G (P < 0.05), and Ex(15P) had the negative correlation with postoperative TBil and GGT (P < 0.05).

CONCLUSIONSThis study has established a method of 3-D liver function evaluation system on an animal model. Among the indexes, Ex(15) can exactly represent the whole liver function while Ex(15P) and HLI(5P) can predict the liver function after the liver resection. The results may help the future clinical use of this technique to evaluate the risk of operation.

Animals ; Hepatectomy ; Liver ; diagnostic imaging ; physiopathology ; surgery ; Liver Cirrhosis, Experimental ; diagnostic imaging ; physiopathology ; surgery ; Liver Function Tests ; Liver Neoplasms, Experimental ; diagnostic imaging ; physiopathology ; surgery ; Postoperative Period ; Rabbits ; Tomography, Emission-Computed, Single-Photon

OBJECTIVESTo study the effectiveness of the lidocaine test in evaluating the liver reserve of rats with experimental liver injury in different phases.

METHODS40 healthy male Wistar rats were divided randomly into experimental and control groups. Rats of the experimental group received subcutaneous CCl4 in oil injection, and rats of the control group received saline injections. Monoethylglycinexylidide (MEGX) test, common hepatic function tests and histological examination of the livers were performed on all the rats.

RESULTSWith the development of the severity in liver injury, the concentrations of the serum MEGX in lidocaine test decreased gradually, which were consistent with liver histological changes. However, the results from the common liver function tests were all abnormal in the experimental group and were not consistent with the liver histological changes.

CONCLUSIONThe results obtained from the MEGX test are more agreeable to liver histological changes than those from common liver function tests. The results from the MEGX test can represent liver histological changes concisely.

Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Lidocaine ; analogs & derivatives ; Liver ; pathology ; physiopathology ; Liver Cirrhosis, Experimental ; chemically induced ; pathology ; physiopathology ; Liver Function Tests ; Male ; Random Allocation ; Rats ; Rats, Wistar

To investigate the role of heme oxygenase(HO), a catalyzing enzyme of heme to produce CO, in modulation of systemic circulation in CCl4-induced cirrhotic rats. Saline(vehicle) and ZnPP were s.c. injected into the posterior necks of rats respectively and the rats were then anesthetized by pentobarbital sodium in four hours. Mean arterial pressure (MAP, kPa), heart rate (HR, b/min) and portal pressure (PP, cm/H2O) were measured by indwelling catheter. Plasma CO was determined by Chalmers method. Heme oxygenase acivity was determined by the rate of bilirubin formation. The cirrhotic rats showed significant hyperdynamic circulation indicated by decreased mean arterial pressure [MAP, (15.6+/-1.7) vs (18.9+/-0.9) kPa, t = 4.52, P less than 0.01] and increased portal pressure [PP, (16.7+/-0.8) vs (8.8+/-0.3) cm H2O, t = 23.10, P less than 0.01] as compared to normal control rats(NS). ZnPP could cause a significant increase in MAP [(17.3+/-1.5) vs (15.6+/-1.7) kPa, t = 2.18, P less than 0.05] and significant decrease in PP [(13.2+/-0.7) vs (16.7+/-0.8) cm H2O, t = 8.53, P less than 0.01] in cirrhotic rats. The cirrhotic group presented a significant increase in plasma CO [(18.0+/-1.9) vs (10.4+/-1.3)mumol/L, t = 8.42, P less than 0.01] and HO activity in the spleens [(11.1+/-0.9) vs (6.5+/-0.9) nmol bilirubin/mg protein/h, t = 9.28, P less than 0.01] and intestines [(2.5+/-0.1) vs. (1.3+/-0.2) nmol bilirubin/mg protein/h, t = 15.1, P less than 0.01]. ZnPP could cause significant decreases in plasma CO and HO activity in liver, spleen and intestine of both control and cirrhotic rats. HO-CO system activation may be an important reason for the hemodynamic disturbance of liver cirrhosis.
Animals ; Carbon Monoxide ; metabolism ; Heme Oxygenase (Decyclizing) ; metabolism ; Hemodynamics ; Liver ; physiopathology ; Liver Cirrhosis, Experimental ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of Cordyceps sinensis (CS) on pancreatic islet B cells of experimental hepatic fibrogenesis rats.

METHODSRats were randomly allocated into three groups: normal group, model group and CS group. The rats in the latter two groups were administered with CCl(4) solution to induce liver fibrosis, the CS group was also treated with CS 10 days after the beginning of CCl(4) administration. Rats in normal group were sacrificed at the beginning of the experiment, while the rats in the other two groups were sacrificed randomly at the end of the third and sixth weeks. The rats' islets were isolated and cultured in vitro, then the basal insulin level of the islets and the serum level of insulin were determined by radioimmunological assay.

RESULTSIt seemed no change that the levels of serum insulin and basal insulin between the model group and the normal group at the third week. But at the sixth week, both insulin levels in the model group were higher than those in the normal group (52.6 mU/L2.5 mU/L vs 23.7 mU/L 2.3 mU/L, q=13.01, p<0.05; 52.94muU/ml 13.12muU/ml vs 35.16muU/ml 5.64muU/ml, q=10.06, p<0.01). No significant change could be seen in the serum levels of insulin between the CS group and the model group at the third and sixth weeks. But the basal insulin levels in the CS group were apparently higher than those in the model group at the third and sixth weeks (156.63muU/ml 6.57muU/ml vs 39.64muU/ml 3.95muU/ml, q=66.94, p<0.001; 140.44muU/ml 38.53muU/ml vs 52.94muU/ml 13.12muU/ml, q=12.98, p<0.01).

CONCLUSIONCordyceps sinensis can increase the basal insulin level of the islets in CCl(4)-induced liver fibrosis rats.

Animals ; Carbon Tetrachloride ; toxicity ; Cordyceps ; Female ; Insulin ; blood ; secretion ; Islets of Langerhans ; physiopathology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; pathology ; physiopathology ; therapy ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the role of perfusion-weighted magnetic resonance imaging (MRI) in evaluation of cirrhotic liver.

METHODSWith a 4F catheter, 1% diluted carbon tetrachloride (1 ml/kg) was selectively injected into right or left hepatic artery of 12 dogs fortnightly. The half liver into which carbon tetrachloride was injected was called as study side (SS), while the other half liver without carbon tetrachloride injection was called as study control side (SCS). Conventional and perfusion-weighted MRI were performed in every 4 weeks. Via a 4F catheter, 5ml gadolinium diethylentriamine pentaaceti acid (Gd-DTPA) dilution was injected into superior mesenteric artery at the 5th scan. The signal intensity-time curves of SS, SCS, and portal vein were completed in MR workstation. The maximal relative signal increase (MRSI), peak time (tp), and slope of the curves were measured.

RESULTSOn conventional MR images, no abnormalities of externality and signal intensity were observed in both SS and SCS of liver at each stage. The mean tp, MRSI, and slope of intensity-time curves in normal liver were 10.56 seconds, 1.01, and 10.23 arbitrary unit (au)/s, respectively. Three parameters of curves didn't show obvious change in SCS of liver at every stage. Abnormal perfusion curves occurred in SS of liver at the 12th week after the 1st injection. The abnormality of perfusion curve in SS was more and more serious as the times of injection increased. The mean tp, MRSI, and slope intensity-time curves in SS of liver were 19.45 seconds, 0.43, and 3.60 au/s respectively at the 24th week.

CONCLUSIONPerfusion-weighted imaging can potentially provide information about portal perfusion of hepatic parenchyma, and to some degree, reflect the severity of cirrhosis.

Animals ; Carbon Tetrachloride Poisoning ; Dogs ; Gadolinium DTPA ; Image Enhancement ; instrumentation ; Liver ; pathology ; ultrastructure ; Liver Circulation ; physiology ; Liver Cirrhosis, Experimental ; diagnosis ; physiopathology ; Magnetic Resonance Imaging ; instrumentation ; methods

Animals ; Liver ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; physiopathology ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Platelet-Derived Growth Factor beta ; metabolism

Adrenomedullin ; Animals ; Endothelin-1 ; blood ; Liver Cirrhosis, Experimental ; physiopathology ; Nitric Oxide ; blood ; Peptides ; blood ; pharmacology ; Portal Pressure ; drug effects ; Rats ; Rats, Wistar

OBJECTIVETo observe the occurrence and progression of liver fibrosis induced by pig serum exposure and bile duct ligation, and analyze the relationship between hepatic inflammation and liver fibrosis.

METHODSChronically immune-mediated liver fibrosis was induced in rats by weekly injection of pig serum (IPS) into the peritoneal cavity at 3 ml/kg for 12 weeks. Cholestatic fibrosis was induced by common bile duct ligation (BDL). The Knodell score was used to evaluate the histological changes in the liver, and immunohistochemistry was performed using anti-SMA, anti-ED1, anti-CK7, and anti-CD45 antibodies. Quantitative real time PCR (qPCR) analysis was employed to quantify the mRNA expression of the genes related to inflammation, including interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), transforming growth factor-beta, platelet-derived growth factor A, as well as the genes associated with fibrogenesis, namely collagen 1, alphaSMA, MMP-9 and TIMP-1.

RESULTSKnodell scores for periportal necrosis, intralobular degeneration and focal necrosis, and portal inflammation were all significantly higher in the BDL group than in the IPS group (P<0.01), whereas the scores for fibrosis was higher in the IPS group (P<0.05). Immunohistochemistry showed obvious inflammation with numerous alphaSMA-positive cells in the liver of the rats in BDL group; the liver of the rats in IPS group showed numerous alphaSMA-positive myofibroblasts with limited inflammatory cell infiltration. qPCR demonstrated a significant up-regulation of the genes related to extracellular matrix remodeling such as collagen 1 (P<0.01), alphaSMA (P<0.01), MMP-9 (P<0.01) and TIMP-1 (P<0.01) in the rat liver in IPS group compared with those in the normal control group, and the mRNA expressions of the inflammation-related cytokines, except for RANTES, were comparable with those in the control. In contrast, the BDL group showed a significant up-regulation of all the pro-inflammatory genes examined with also increased expression of the fibrogenesis-related genes (P<0.05).

CONCLUSIONLiver fibrosis induced by IPS is characterized by active ECM remodeling in the absence of obvious inflammation, indicating that chronic development of liver fibrosis can be independent of active hepatic inflammation. BDL-induced liver fibrosis highlights obvious inflammation and fibrous proliferation in the liver.

Animals ; Bile Ducts ; surgery ; Cholestasis ; complications ; physiopathology ; Ligation ; Liver Cirrhosis, Experimental ; etiology ; immunology ; pathology ; Male ; Rats ; Rats, Inbred F344 ; Serum ; immunology ; Swine