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Segmental ischemia of the liver - microdialysis in a novel porcine model.
Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
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2009 (English)In: European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes, ISSN 1421-9921, Vol. 43, no 3, 276-285 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Segmental liver ischemia is often used in rodents to study ischemia and reperfusion injuries (IRI). There are no reports of protocols using segmental ischemia in porcine models. Microdialysis (MD) provides the opportunity to study local effects of IRI in vivo. METHODS: Eight pigs received an MD catheter placed in liver segments IV and V, respectively. All circulation to segment IV was stopped for 80 min, and reperfusion was followed for 240 min. RESULTS: During ischemia the levels of lactate, glycerol and glucose increased 3-fold (p < 0.001), 40-fold (p < 0.001) and 4-fold (p < 0.01), respectively, in the ischemic segment compared to the perfused segment, whereas the levels of pyruvate fell to a tenth of the preischemic level (p < 0.001). All values returned to baseline after reperfusion. Serum levels of aspartate aminotransferase increased (p < 0.05). Polymorphonuclear cells increased in both segments, although the density was significantly higher in segment IV. CONCLUSION: Clamping of one liver segment in pigs is a simple, stable and reproducible model to study IRI with minimal systemic effects. MD revealed no signs of anaerobic metabolism in the perfused segment but still there was an increase in the number of polymorphonuclear neutrophils in this segment, although it was lower than that in the ischemic segment.

Place, publisher, year, edition, pages
2009. Vol. 43, no 3, 276-285 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-21350DOI: 10.1159/000230675PubMedID: 19641322OAI: oai:DiVA.org:liu-21350DiVA: diva2:241093
Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2011-05-26
In thesis
1. Microdialysis in Liver Ischemia and Reperfusion injury
Open this publication in new window or tab >>Microdialysis in Liver Ischemia and Reperfusion injury
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: New chemotherapy regimens and improvements in surgical technique have increased the number of patients with liver tumours eligible for curative liver resection. There is a significant risk of bleeding during liver surgery, but this risk can be reduced if the portal inflow is temporarily closed; i.e. the Pringles maneuver (PM). If the PM is used, the liver will suffer from ischemia and reperfusion injury (IRI). If the liver remnant is too small or if the patient has chronic liver disease, the IRI may inhibit the regeneration of the liver remnant. The patient may then die from postoperative liver failure. Several strategies have been tried to protect the liver from IRI. For instance can the PM be applied in short intervals or reactive oxygen species can be scavenged by antioxidants. There are no sensitive methods available for studying IRI in patients and little is known how IRI affects the metabolism in the liver. Microdialysis is a technique that allows for continuous sampling of interstitial fluid in the organ of interest

Aim: To investigate the effects of ischemia and reperfusion on glucose metabolism in the liver using the microdialysis technique.

Method: A porcine model of segmental ischemia and reperfusion was developed. The hepatic perfusion and glucose metabolism was followed for 6-8 hours by placing microdialysis catheters in the liver parenchyma (studies I-III). In study IV, 16 patients were randomized to have 10 minutes of ischemic preconditioning prior to the liver resection, which was performed with 15 minutes of ischemia and 5 minutes of reperfusion repetitively until the tumour(s) were resected.

Results: During ischemia the glucose metabolism was anaerobic in the ischemic segment, while the perfused segment had normal glucose metabolism. Urea was added in the perfusate of the microdialysis catheters and was found to be a reliable marker of liver perfusion. The antioxidant NAcetylcystein (NAC) improved the hepatic aerobic glucose metabolism in the pig during the reperfusion, shown as reduced levels of lactate and improved glycogenesis in the hepatocytes. This can be explained by the scavenging of nitric oxide by NAC as nitric oxide otherwise would inhibit mitochondrial respiration. Also IP improved aerobic glucose metabolism resulting in lower hepatic lactate levels in patients having major liver resections.

Conclusion: Microdialysis can monitor the glucose metabolism both in animal experimental models and in patients during and after hepatectomy. Both NAC and IP improves aerobic glucose metabolism, which can be of value in patients with compromised liver function postoperatively.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 86 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1238
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68651 (URN)978-91-7393-190-8 (ISBN)
Public defence
2011-06-10, Nils Holger, Hälsouniversitetet, Campus US. Linköpings universitet, Linköping, 09:00 (English)
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Available from: 2011-05-26 Created: 2011-05-26 Last updated: 2015-06-05Bibliographically approved

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Winbladh, AndersSandström, PerOlsson, HansSvanvik, Joar

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Department of Surgery in ÖstergötlandDepartment of Clinical and Experimental MedicineFaculty of Health SciencesSurgery Molecular and Immunological Pathology Department of Clinical Pathology and Clinical Genetics
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