a-rat-model-orthotopic-liver-transplantation-using-novel-magnetic

A Rat Model of Orthotopic Liver Transplantation Using a Novel Magnetic Anastomosis Technique for Suprahepatic Vena Cava Reconstruction

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep ...

Tianjin First Center Hospital

To improve the technique of suprahepatic vena cava (SHVC) reconstruction in rat OLT, novel magnetic rings were designed and manufactured to facilitate reconstruction of SHVC and shorten the anhepatic time. One-hundred and twenty adult male Wistar rats were randomly divided into two groups: rings group (n = 30), using magnetic rings for SHVC reconstruction; suture group (n = 30), 7/0 prolene suture was used for SHVC running anastomosis as control. Cuff techniques were used for portal vein and infrahepatic vena cava reconstruction as Kamada and Calne described. The bile duct was reconnected with a stent. The hepatic re-arterialization was omitted. In the rings group, the SHVC reconstruction took 0.91 ± 0.24 (mean ± SD) min; the anhepatic phase and the recipient operation time were 5.63 ± 0.65 min and 36.02 ± 8.02 min, respectively. In suture group, the anastomotic time of SHVC was 10.40 ± 2.11 min; the anhepatic phase and the recipient operation time were 17.76 ± 2.51 and 49.38 ± 12.06 min, respectively, and there was statistically significant difference between the two groups. The ALT levels reached peak at 24 h post-OLT (186.2 ± 32.5 IU/l) and restored to normal level at 96 h gradually. In the rings group, 29 of 30 rats survived at day 7 and 28 of 30 rats survived at day 30. In contrast, only 25 of 30 recipients in suture group remained alive at day 7 and 22 of 30 remained alive at day 30 (P < 0.05). Better anastomotic healing was founded in rings group by pathology and scanning electron microscope. The magnetic rings technique provides a novel, simple method for SHVC reconstruction of OLT in rat. It significantly shortens anhepatic phase, while the success rate of the operation is satisfactory.

Magnetic ring anastomosis of suprahepatic vena cava: novel technique for liver transplantation in rat.

Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation.

CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction.

AbstractRadical resection is the first choice for hepatic alveolar echinococcosis (HAE). However, many patients with advanced HAE have no chance to be treated with curative resection owing to the long clinical latency. This study aimed to evaluate the necessity of aggressive operations, like palliative resection and orthotopic liver transplantation (OLT), in the management of advanced HAE. A retrospective study analyzed 42 patients with advanced HAE treated with palliative resection (= 15), palliative nonresective procedures (= 13), OLT (= 3), or albendazole therapy alone (= 11). The patients' condition before treatments was comparable among all the four groups. The overall 1-year, 3-year, and 5-year survival rates of the 42 cases were 81.0%, 45.2%, and 23.8%, respectively. No event occurred to end the follow-up during the 5-year observation period except death. The survival time (median ± standard error) of the palliative resection group (3.6 ± 1.4 years) was longer than that of the palliative nonresective procedures group (1.5 ± 0.2) and the albendazole therapy-alone group (1.0 ± 0.4). The 5-year survival rates after palliative resection and liver transplantation were 40.0% and 66.7%, compared with only 7.7% and 9.1% after palliative nonresective procedures or albendazole therapy alone. Therefore, we concluded that aggressive treatment with a multimodality strategy could contribute to prolonged survival in patients with advanced HAE. Moreover, the prognosis of the patients who received albendazole therapy alone or palliative nonresective procedures is poor.

Management of Advanced Hepatic Alveolar Echinococcosis: Report of 42 Cases.

To reproduce a stable animal model of brain death in pigs, observe the change regularity of cerebral oxygen metabolism during the process of brain death, and to evaluate the significance and value of cerebral oxygen metabolism parameters for the diagnosis of brain death.

[Experimental animal study of cerebral oxygen metabolism changes during the process of brain death].

BACKGROUND Studies have shown that normothermic machine perfusion (NMP) exerts a significant protective role for donations after cardiac death (DCD) livers and verified the effects of NMP in preservation, repair, and preoperative assessment of human donor livers. The objective of this study was to verify the effectiveness and stability of NMP system by splitting pig livers in perfusion preservation. MATERIAL AND METHODS Four healthy Ba-Ma miniature pigs were used. The livers were harvested, and then connected to the NMP system to split the livers. The indexes during the splitting were recorded, the serological indices were measured, and routine pathological examination of liver tissue were observed. RESULTS With splitting, the portal vein pressure and the hepatic artery pressure were not significantly changed. The flow in the portal vein and hepatic artery reduced respectively from 455±107.55 mmHg, 180.75±59.46 mmHg before splitting to 392.5±125.27 mmHg and 126.25±6.99 mmHg after splitting. The liver preservation temperature was controlled to 38.83±0.24 to 38.93±0.43°C during splitting. At the beginning of perfusion preservation, the alanine aminotransferase(ALT), lactate dehydrogenase(LDH), and alkaline phosphatase (ALP) were lower than the baseline level; ALT and LDH gradually increased with splitting, whereas ALP was maintained in a lower level in the splitting. At the beginning of perfusion preservation, aspartate aminotransferase(AST) was comparable with the baseline value, and it was gradually increased with splitting. The cell structure in the liver before NMP preservation and after splitting did not show significant changes. CONCLUSIONS The NMP device developed in this study can be used for donor liver preservation and splitting, without causing significant liver damage.

Article	Year
Magnetic ring anastomosis of suprahepatic vena cava: novel technique for liver transplantation in rat. Transplant international : official journal of the European Society for Organ Transplantation\| PubMed ID: 25132515	2015
CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction. Journal of immunology research\| PubMed ID: 28053995	2016
Management of Advanced Hepatic Alveolar Echinococcosis: Report of 42 Cases. The American journal of tropical medicine and hygiene\| PubMed ID: 28070011	2017
[Experimental animal study of cerebral oxygen metabolism changes during the process of brain death]. Zhonghua wei zhong bing ji jiu yi xue\| PubMed ID: 28743344	2017
Development and Assessment of Normothermic Machine Perfusion Preservation for Extracorporeal Splitting of Pig Liver. Annals of transplantation\| PubMed ID: 28827516	2017
Retracted: Normothermic machine perfusion protects against liver ischemic reperfusion injury during reduced-size liver transplantation in pigs. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society\| PubMed ID: 29316214	2018

Yuan Shi

Biography

JoVE Journal Publications

Other Publications