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Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
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.
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2010 (English)In: EUROPEAN SURGICAL RESEARCH, ISSN 0014-312X, Vol. 45, no 2, 105-112 p.Article in journal (Refereed) Published
Abstract [en]

Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

Place, publisher, year, edition, pages
S. Karger AG , 2010. Vol. 45, no 2, 105-112 p.
Keyword [en]
Liver perfusion, Lactate, Ethanol, Metabolism, Recovery
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-62299DOI: 10.1159/000319868ISI: 000283851400006OAI: oai:DiVA.org:liu-62299DiVA: diva2:372579
Available from: 2010-11-26 Created: 2010-11-26 Last updated: 2012-03-20
In thesis
1. On microvascular blood flow assessment with the new microdialysis urea clearance technique
Open this publication in new window or tab >>On microvascular blood flow assessment with the new microdialysis urea clearance technique
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to develop and evaluate a new way of monitoring blood flow with microdialysis. A thin catheter consisting of a semipermeable membrane is implanted in the tissue being studied. The catheter is perfused by a solution that closely resembles interstitial fluid, and small water-soluble substances are allowed to diffuse passively through the pores of the membrane with the aim at reaching equilibrium with the surrounding tissue.  The minimally invasive character of microdialysis, and its ability to sample from the organ being studied, make microdialysis attractive in most research settings as well as for clinical surveillance. It has, however, become increasingly evident that microdialysis under conditions of non-equilibrium - for example, fluctuating regional blood flow, will alter the results gained. We have therefore aimed to explore the possibilities of developing a new marker of blood flow that will yield information about changes in blood flow that occur in the area of the microdialysis catheter itself.

We hypothesised that the changes in the diffusion of exogenous urea could be used as markers of changes in tissue blood flow. The theoretical basis for this approach is that the mass transfer of urea will increase across the dialysis membrane secondary to increased blood flow. As removal of urea from the vicinity of the dialysis membrane increases with increased blood flow, the concentration gradient of urea between the perfusate and tissue will also increase. This in turn will result in a greater loss of urea from the perfusate. The changes noted in retrieval of urea from dialysate by the system are therefore thought to be inversely related to changes in blood flow. We tested our hypothesis in two species of animal (rat and pig) and in man, and in three organ systems (muscle, liver, and skin), and present four papers that indicate that the urea clearance technique provides reliable and reproducible results. The technique was evaluated against conventional metabolic markers (lactate and glucose), the ethanol clearance technique (microdialysis), laser Doppler perfusion imaging (LDPI), and polarisation light spectroscopy (TiVi).

We present evidence that the urea clearance technique can be used to assess blood flow in the organs studied reliably and reproducibly with microdialysis. The microdialysis technique is minimally invasive and safe for the recipient, and catheters can easily be implanted during operation to monitor organs at risk. Urea is easily analysed as a standard assay among other “basic” metabolic markers (in a standard microdialysis kit) and has favourable characteristics with a standardised measurement system that is routinely used for monitoring metabolites in the clinic. The technique is also effective when used at lower perfusate flow rates (<1 μl/minute), which is advantageous as the recovery of metabolic markers increases at low perfusate flow rates.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 69 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1204
Keyword
microdialysis, microcirculation
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-63116 (URN)978-91-7393-320-9 (ISBN)
Public defence
2010-12-03, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2010-12-28 Created: 2010-12-11 Last updated: 2012-03-13Bibliographically approved
2. 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)
Opponent
Supervisors
Available from: 2011-05-26 Created: 2011-05-26 Last updated: 2015-06-05Bibliographically approved

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Farnebo, SimonWinbladh, AndersZettersten, ErikSandström, PerSamuelsson, AndersTheodorsson, ElvarSjöberg, Folke

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Farnebo, SimonWinbladh, AndersZettersten, ErikSandström, PerSamuelsson, AndersTheodorsson, ElvarSjöberg, Folke
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SurgeryFaculty of Health SciencesDepartment of Plastic Surgery, Hand surgery UHLDepartment of Clinical and Experimental MedicineDepartment of Surgery in ÖstergötlandDepartment of Anaesthesiology and Surgery UHLAnesthesiologyDepartment of Intensive Care UHLClinical ChemistryDepartment of Clinical ChemistryBurn Center
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