Morva Tahmasbi Rad

Using microdialysis for early detection of vascular thrombosis after kidney transplantation in an experimental porcine model

BACKGROUND In kidney transplantation (KTx), vascular thrombosis has a major impact on morbidity and graft survival. The ischaemia, caused by thrombosis, can lead to interstitial metabolite changes. The aim of this experimental study was to create conditions in which the graft would be prone to vascular thrombosis following KTx and then to evaluate the role of microdialysis (MD) for its early detection. METHODS Sixteen randomized pigs in the control group received heparin and immunosuppressive drugs, while the case group received none. Based on histopathological evidence of vascular thrombosis, the case group was subdivided into mildly and severely congested subgroups. Using MD, we evaluated the interstitial concentrations of glucose, lactate to pyruvate ratio, glutamate and glycerol in the transplanted grafts during different phases of KTx. RESULTS Following reperfusion, we noted considerable changes. The severely congested subgroup showed a low and decreasing level of glucose. Only in this group did the lactate to pyruvate ratio continue to increase until the end of monitoring. The glycerol level increased continuously in the entire case group and this increase was most significant in the severely congested subgroup. In all of the study groups, glutamate concentration remained in a low steady state until the end of monitoring. CONCLUSION MD can be an appropriate method for early detection of vascular complications after KTx. Decreasing glucose levels, increased lactate to pyruvate ratio and increased glycerol levels are appropriate indicators for early detection of vascular thromboses following KTx. Particularly, the glycerol level could predict the necessity and urgency of intervention needed to ultimately save the transplanted kidney.

Reduced glutathione in the liver as a potential viability marker in non-heart-beating donors.

Although the use of non–heart‐beating donors (NHBD) is the oldest type of organ transplantation, the results were and still are disappointing. To consider using a liver from NHBD, it is of importance to assess the graft viability. Our aim was to assess the role of reduced liver glutathione (rGSHL) as a potential predictive marker of liver function before transplantation. Autotransplanted livers were subjected to 0, 60, and 90 minutes of ischemia in 20 pigs. We analyzed systemic cardiocirculatory parameters, bowel ischemia by endotoxin, endotoxin‐neutralizing capacity, oxidative stress, hepatic perfusion parameters, liver enzymes, local bowel ischemia, and liver oxidative stress (rGSHL and oxidized glutathione in the liver). Autotransplantation was comparable to donor explantation/recipient transplantation with respect to systemic and hepatic parameters. Liver ischemia for 0, 60, and 90 minutes resulted in survival in 100% (NHBD‐0), 71% (NHBD‐60), and 57% (NHBD‐90) of animals. Of all parameters, only hepatic microperfusion, pHi of the sigmoid colon, and bowel ischemia by endotoxin in the NHBD‐90 group showed significant changes compared to NHBD‐60 and control animals. Although systemic endotoxin‐neutralizing capacity and total glutathione in erythrocytes levels were mainly influenced by cold perfusion, hepatic oxidative stress increased with ischemia time. The cut‐off value of 11.5 ng/mmol of rGSHL could distinguish survivors from nonsurvivors, independent of the ischemia time. In conclusion, rGSHL has the potential of becoming an important viability marker, as it could predict survival in autotransplantation NHBD model regardless of the ischemia time. Further investigation to declare reasons for differing rGSHL levels within the liver is required. Liver Transpl 14:1637–1647, 2008.

Early Detection of Metabolic Changes Using Microdialysis During and After Experimental Kidney Transplantation in a Porcine Model

Background: Microdialysis (MD) can detect organ-related metabolic changes before they become measurable in plasma through the biochemical parameters. This study aims to evaluate the early detection of metabolic changes during experimental kidney transplantation (KTx). Material and methods: During preparation of 8 donor kidneys, one MD catheter was inserted in the renal cortex and samples were collected. After a 6-hour cold ischemia time (CIT), kidneys were implanted in the 8 recipient pigs. Throughout the warm ischemia time (WIT) and after reperfusion, kidneys were monitored. The interstitial glucose, lactate, pyruvate, glutamate, and glycerol concentrations were evaluated. Results: A significant decline in glucose level was observed at the end of CIT. The lactate level was reduced to the minimum point of 0.35 ± 0.08 mmol/L in CIT. After reperfusion, lactate values raised significantly. During the WIT, the pyruvate level increased, continued until the end of the WIT. For glutamate, a steady increase was noted during explantation, CIT, WIT, and early reperfusion phases. The increase of glycerol value continued in the early postreperfusion, which was then followed by a sharp decline. Conclusion: MD is a fast and simple minimally invasive method for measurement of metabolic substrates in renal parenchyma during KTx. MD offers the option of detecting minor changes of interstitial glucose, lactate, pyruvate, glutamate, and glycerol in every stage of KTx. Through the use of MD, metabolic changes can be continuously monitored during the entire procedure of KTx.

The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation.

Background and introductionWithout adequate prophylaxis, liver transplantation (LTx) is frequently followed by hepatitis B virus (HBV) reinfection, which results in rapidly progressing liver disease and significantly decreased overall survival. In the last two decades, significant progress has been made in the prophylaxis and treatment of HBV.DiscussionWe present an overview of different protocols and regimens used for prophylaxis of HBV reinfection after LTx and describe the protocol implemented at our center. Following LTx, HBV reinfection can be effectively prevented by administration of anti-hepatitis B immunoglobulin (HBIg) alone or more recently in combination with antiviral nucleoside/nucleotide analogs (NUCs). Several studies reported good results with the use of HBIg alone, but combination treatment with HBIg and NUCs has proven to be a superior prophylactic regimen for HBV recurrence. At present, combination therapy (HBIg and a nucleoside or nucleotide analog) is the gold standard used in many transplantation centers. This preventive regimen reduces the risk of a recurrence of HBV infection and thereby the need for re-transplantation. Future and ongoing studies will show how long HBIg must be given after transplantation, especially when used in combination with potent antivirals, such as entecavir or tenofovir.

Comparison of Different Surgical Techniques in Distal Pancreatectomy An Experimental Study in a Porcine Model

Aims. Different surgical transection methods have been used for distal pancreatectomy (DP), but none of them has yet achieved perfect results. This study compares 2 standard transection techniques with the alternative LigaSure technique. Methods. Forty-eight pigs underwent a DP. Sixteen animals were operated on with a scalpel followed by hand suturing. Sixteen pigs received a DP using an Endo GIA, and the pancreas of 16 pigs was transected with LigaSure. The transection surface of remnant pancreas was observed for liquid collection and abscess on postoperative day 7. Results. Operating time on the day of DP was significantly different, with a shorter operating time in the stapler and LigaSure groups. The morbidity on postoperative day 7 was similar in all groups. Conclusion. In the present experimental animal study, LigaSure seems to be fast and safe as well as comparable with the standard transection and closure techniques in DP.

Evaluating the effects of extended cold ischemia on interstitial metabolite in grafts in kidney transplantation using microdialysis.

PurposeDuring kidney transplantation (KTx), the length of cold ischemia time (CIT) and the subsequent changes in energy metabolism may lead to variations in interstitial metabolites. Using microdialysis (MD), we evaluated the effects of a short and long CIT on changes of these metabolites.MethodsSixteen pigs were randomized in two identical groups, one with a short CIT and the other one with a long CIT. Using MD in the transplanted grafts, we evaluated the parenchyma concentrations of glucose, lactate, pyruvate, glutamate and glycerol in different stages.ResultsWe noted that during the warm ischemia time (WIT) and in the early post-reperfusion phase glucose levels increased more significantly in the long CIT group and remained high until the end of monitoring. At the end of CIT and during WIT, the long CIT group had a significantly higher glycerol level, but the level dropped gradually in the late post-reperfusion phase and reached a steady state in both groups.ConclusionsThe extended CIT clearly results in considerably impaired graft metabolism. The high interstitial glucose levels within hours after KTx could be considered as a marker of primary delayed function of the graft. Furthermore, the glycerol value could reflect the extent of graft injury during the ischemia time or in case of acute impairment of graft perfusion.

A Simplified Technique of Pancreas Transplantation in a Porcine Model

Background: The incidence of diabetes has been steadily increasing. The only curative option for diabetes is pancreas transplantation (PTx). Porcine models are valuable because of their anatomical and physiological similarities to human beings. Our aim is to introduce a simplified technique of PTx in a porcine model. Methods: In Landrace pigs (n = 32), after median laparotomy, the pancreas was mobilized, and the portal and splenic veins were divided. The proper hepatic and splenic arteries and the bile duct were also prepared, and the duodenal bulb was prepared and stapled. The third portion of the duodenum was freed up to the ligament of Treitz and stapled, and the renal arteries were ligated. After systemic heparinization, the pancreas was perfused through the abdominal aorta with histidine-tryptophan-ketoglutarate solution. The portal and splenic veins were cut for evaluating the sufficiency of perfusion. Whole pancreaticoduodenal graft was procured along with an aortic jump graft containing mesenteric and celiac trunks. In recipients, after total pancreatectomy, the suprarenal inferior vena cava and infrarenal aorta were prepared for vascular anastomosis in an end-to-side manner. After pancreas reperfusion, duodenoduodenostomy was performed in an end-to-side manner. Results: Median cold and warm ischemia times were 10 h (range, 9-14 h) and 50 min (range, 35-80 min), respectively. The hemodynamic status was stable throughout the operation. The median follow-up period was 7 days (range, 4-10). There were no major intra- and postoperative complications. Conclusion: By using an aortic jump graft, there was no need to perform additional arterial reconstruction resulting in a short warm ischemic and operation time. End-to-side portocaval and duodenoduodenal anastomoses make this model of PTx a very feasible method for experimental evaluations.

Laparoscopically Assisted Vaginal Hysterectomy in a Patient With Micro-Invasive Cervical Cancer After Two Liver Transplantations

BACKGROUND Advances in surgical techniques and immunosuppressive therapy have improved graft survival in transplant recipients. However, intense long-term immunosuppression increases the incidence of cancer in these patients compared with the general population, not least because of viral infections. Cervical cancer is the third most common malignancy worldwide. In early invasive cervical cancer, surgery is the treatment of choice. CASE In 2010, we performed a laparoscopically assisted vaginal hysterectomy (LAVH) in a 42-year-old patient with micro-invasive cervical adenocarcinoma (FIGO stage IA1) who had undergone two liver transplantations in 2006 and 2008. The patient was followed up for 18 months after surgery. Despite upper abdominal adhesions and minor difficulties in inserting the Veress needle, the pneumoperitoneum was created safely. The procedure was completed within 157 minutes without any intraoperative complications. Blood loss was less than 100 mL. Postoperative course was uncomplicated with minimal fluctuations in liver function markers. Immunosuppressive therapy was continued without modification. The patient was discharged on postoperative day 9. No complications or recurrence were reported during the 18-month follow-up. CONCLUSIONS The laparoscopic approach is a justifiable form of surgical management in the treatment of a liver transplant recipient with early-stage cervical cancer.