A Novel and Sensitive Approach for the Evaluation of Liver Ischemia-Reperfusion Injury After Liver Transplantation

Brandlhuber, Martina; Armbruster, Marco; Zupanc, Blaz; Coan, Paola; Brun, Emmanuel; Sommer, Wieland und Rentsch, Markus (2016): A Novel and Sensitive Approach for the Evaluation of Liver Ischemia-Reperfusion Injury After Liver Transplantation. In: Investigative Radiology, Bd. 51, Nr. 3: S. 170-176

Abstract

Objectives The purpose of our study was to evaluate the potential of x-ray propagation-based phase-contrast imaging (PCI) computed tomography (CT) for the detection and characterization of early changes after ischemia-reperfusion (IR) in a standardized rat liver transplantation (LTx) model. Materials and Methods Syngeneic orthotopic liver transplantation was performed in male Lewis rats. Ischemia-reperfusion injury (IRI)-induced changes of liver parenchyma were investigated in a time-dependent manner (2, 16, 24, and 32 hours). X-ray phase-contrast images of formalin-fixated liver specimens were acquired in CT mode by using a voxel size of 8 x 8 x 8 mu m(3). Necrapoptotic cell death was visualized with the TdT-mediated dUTP-biotin nick end labeling technique, and alterations of liver graft microhemodynamics, that is, acinar and sinusoidal perfusion failure, were evaluated by in vivo fluorescence microscopy. Results Acquired and reconstructed PCI-CT images showed an increase in necrotic liver parenchyma dependent on cold storage time, measuring 5.7% +/- 1.6% after 2 hours (comparable to 2.6% +/- 0.4% for sham livers), 11.5% +/- 2.1% (16 hours;P < 0.05 vs control), 23.0% +/- 0.5% (24 hours;P < 0.001 vs control), and 31.3% +/- 2.2% (32 hours;P < 0.001 vs control). There were a significant lower number of perfused acini in dependence on increasing cold storage time. The acinar perfusion index reached 0.970 +/- 0.006 after 2 hours of cold ischemia (comparable to 0.960 +/- 0.009 for sham livers) and declined continuously after 16, 24, and 32 hours cold ischemia (0.58 +/- 0.03, 0.49 +/- 0.02, 0.41 +/- 0.03, each P < 0.0001 vs controls). Comparable results were found for sinusoidal perfusion, reaching 1.8% +/- 0.4% of nonperfused sinusoids for 2 hours of cold ischemia and 8.2% +/- 0.8% after 16 hours, 18.8% +/- 1.4% after 24 hours, and 39.0% +/- 2.4% after 32 hours (each P < 0.0001 vs controls). Prolonged cold ischemia was associated with an increasing number of TdT-mediated dUTP-biotin nick end labeling-positive cells (hepatocytes and sinusoidal lining cells), reaching 0.4 +/- 0.1 (sham), 0.7 +/- 0.4 (2 hours), 6.4 +/- 1.1 (16 hours), 2.1 +/- 0.3 (24 hours), and 14.7 +/- 3.5 (32 hours;P = 0.002) for hepatocytes. Conclusions X-ray PCI of histological liver specimens can detect IR-induced tissue necrosis and can provide detailed complementary 3-dimensional information to standard histopathologic findings.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0020-9996
• Sprache: Englisch