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Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis
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. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
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2012 (English)In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 176, no 1, 55-62 p.Article in journal (Refereed) Published
Abstract [en]

Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.

Place, publisher, year, edition, pages
Elsevier , 2012. Vol. 176, no 1, 55-62 p.
Keyword [en]
ischemia-reperfusion injury; preconditioning; remote preconditioning; liver ischemia; liver surgery; microdialysis
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-79791DOI: 10.1016/j.jss.2011.07.038ISI: 000305210100018OAI: diva2:544995
Available from: 2012-08-17 Created: 2012-08-14 Last updated: 2014-09-08
In thesis
1. Methods to Reduce Liver Ischemia/Reperfusion Injury
Open this publication in new window or tab >>Methods to Reduce Liver Ischemia/Reperfusion Injury
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: During the last two decades, liver surgery has expanded enormously, partly due to improved surgical equipment and techniques as well as new and more powerful chemotherapy agents. As the liver is a very well-vascularized organ, there is an inherent risk of bleeding during liver resection. One of the most popular methods employed to reduce this risk is to close the vascular inflow to the liver using the Pringle’s maneuver (PM). However, this procedure has been recognized to cause ischemia/reperfusion injury (IRI) to the future liver remnant (FLR). In cases of extensive resection where the FLR is small and in cases when the liver suffers from chronic diseases, such as cirrhosis, IRI can greatly increase the risk of post-operative liver failure (POLF). Ischemic preconditioning (IPC) and, more recently, remote ischemic preconditioning (R-IPC) are methods that have been employed to reduce IRI.

Aim: 1) To compare the effects of IPC and R-IPC in a rat model; 2) to investigate the clinical effect of IPC during modern liver surgery; 3) to investigate the role of the nitric oxide (NO) system in IRI, IPC and R-IPC; and 4) to explore the possible protective effects of nitrite administration before IRI.

Methods: A rat model of segmental ischemia followed by 4 hours of reperfusion including microdialysis (μD) was developed from earlier models. The effects of IPC and R-IPC were compared using transaminases and histology as well as continuous μD sampling for glucose, pyruvate, lactate and glycerol. The role of the NO system was examined by serum and μD measurements of NOx as well as tissue measurements of iNOS mRNA and IL-1R mRNA. In study II, patients were randomized to IPC or no IPC prior to liver resection, where intermittent PM was used to decrease bleeding.

Results: IPC was more effective in protecting the liver against IRI than R-IPC, as indicated by the levels of transaminases. Lower lactate levels were detected in patients treated with IPC before major liver resections than in controls. IPC reduced iNOS mRNA transcription during reperfusion; this result may be related to the early but not sustained increases in IL-1R transcription observed in the IPC group. Nitrite administered before ischemia reduced AST and ALT levels in the level after 4 hours of reperfusion; in addition, necrosis and glycerol release from the ischemic liver were reduced as well.

Conclusion: IPC is more effective than R-IPC in animal models; however, this effect is unlikely to be of clinical importance. NOx decreases in the ischemic liver and the administration of nitrite before ischemia reduces IRI in rats. This may have clinical implications in the future.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 136 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1418
National Category
Clinical Medicine Basic Medicine
urn:nbn:se:liu:diva-110318 (URN)10.3384/diss.diva-110318 (DOI)978-91-7519-245-1 (print) (ISBN)
Public defence
2014-10-17, Aulan, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Available from: 2014-09-08 Created: 2014-09-08 Last updated: 2014-09-08Bibliographically approved

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Björnsson, BergthorWinbladh, AndersBojmar, LindaTrulsson, LenaOlsson, HansSundqvist, TommyGullstrand, PerSandström, Per
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Department of Clinical and Experimental MedicineFaculty of Health SciencesSurgeryMolecular and Immunological PathologyDepartment of Clinical Pathology and Clinical GeneticsMedical MicrobiologyDepartment of Surgery UHLDepartment of Surgery in Östergötland
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