Liver fibrosis is based on complex interactions between extracellular matrix-producing hepatic stellate cells and is defined as excessive matrix deposition and an abundance of infiltrating cells in the liver. Studying these processes requires in vitro and in vivo experimental work on animals. In fibrosis research, experimental work in rodents is currently the gold standard for confirming a proposed disease-associated mechanism. Bile duct ligation (BDL) induces obstructive jaundice resulting in cholestasis. BDL is useful for preclinical research studies of liver injury due to extrahepatic cholestasis such as apoptosis and fibrosis. Here we provide a stepwise surgical approach to resect the common bile duct and monitor in situ hepatic metabolism by microdialysis.

Introduction: Levosimendan is a positive inotropic molecule that does not reduce splanchnic circulation and has anti ischemic properties by opening mito KATP channels. Cirrhosis is a chronic and diffuse process characterized by fibrosis and the conversion of typical liver architecture into structurally abnormal nodules. In the late stages of the disease, cirrhosis is responsible for organ failure and complications such as cirrhotic cardiomyopathy and hepatic encephalopathy. Material and methods: We examined the effect of levosimendan in rat models of liver cirrhosis. Male Wistar rats were divided into four groups: Group A: cirrhotic rats 14 days after bile duct ligation (BDL); Group B: control (intact rats); Group A1: BDL and levosimendan (liver cirrhosis induced by bile duct ligation plus intraperitoneal administration of levosimendan); Group B1: control and levosimendan (intact animals with normal liver function treated with an intraperitoneal injection of levosimendan). Each group was subjected to blood sampling to determine GOT, GPT, and bilirubin at baseline, two weeks after surgery, and four days after treatment. In addition, echocardiography was performed in all the groups simultaneously. At the end of the experiments, the rats were subjected to cerebral and hepatic microdialysis and sacrificed. Results: Serum GOT, GPT, and bilirubin in Group A1 (GOT 304 UI/L, GPT 60 UI/L, BIL 3,9 mg/dl) were considerably lower than in Group A (GOT 320 UI/L, GPT 67,16 UI/L, BIL 6,4 mg/dl). The Ejection fraction value decreased significantly postoperatively in Group A (preop 55,66%, BDL 38,85%) and was highest after treatment with levosimendan (Group A1 48,38%). Significant histological differences were detected between the experimental groups (Group A Sheuer staging 3, severe fibrosis, Group A1 Sheuer staging 0-2 no, mild and moderate fibrosis). Group A had a higher value of Lactate, Pyruvate, Glycerol, and Glutamate cerebral microdialysate concentrations (Lac 0.37mM, Pyr 16.25 mcM, Glyc 15.72 mcM, Glut 15.8 mcM) in comparison with BDL rats treated with levosimendan (Group A1 - Lac 0.31 mM, Pyr 6.3 mcM, Glyc 13.66 mcM, Glut 11.15 mcM). Glucose concentrations in cerebral dialysate from Group A were significantly lower (0.13 mM) than in Group A1 (0.25 mM). Glucose and Glycerol concentrations in liver microdialysate from Group A were significantly lower (Gluc 0.95 mM, Glyc 1 mcM) than in Group A1 (Gluc 1.6 mM, Glyc 3.4 mcM). Conversely, in liver dialysate from Group A (0.52 mM), lactate was significantly higher than in Group A1 (0.35 mM). Conclusions: Our results suggest that levosimendan can be potentially protective for fibrotic liver and probably can prevent cirrhosis complication as cirrhotic cardiomyopathy and hepatic encephalopathy.

Monitoring and measuring magnesium (Mg) values are essential to prevent the development of numerous complications in perioperative medicine and critically ill patients. Although previous studies suggest that measuring free ionized magnesium (iMg) is more useful for estimating Mg status, clinicians currently rely on measurement of total serum magnesium to determine if supplemental magnesium is needed. In this review, we analyzed the recent literature to decide whether it is better to measure ionized serum Mg or total serum Mg when assessing magnesium status, whether iMg predicts clinical outcome, and what are the difficulties in measuring serum iMg levels in intensive care patients and perioperative medicine.