Preservation of Microvascular Integrity in Murine Orthotopic Tracheal Allografts by Clopidogrel
Heim C, Khan MA, von Silva-Tarouca B, Kuckhahn A, Stamminger T, Ramsperger-Gleixner M, Nicolls MR, Weyand M, Ensminger SM (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 103
Pages Range: 899-908
Journal Issue: 5
DOI: 10.1097/TP.0000000000002571
Abstract
BACKGROUND: Survival after lung transplantation is mainly limited by the development of chronic lung allograft dysfunction (CLAD). The aim of this study was to investigate if platelet inhibition by clopidogrel has a functionally relevant influence on the microvascular integrity of orthotopic tracheal allografts as an anatomic basis for the development of CLAD. METHODS: We orthotopically transplanted C57Bl/6 (H-2) tracheas into CBA.J (H-2) recipients who afterwards received clopidogrel (1 mg/kg). Morphometric analysis was performed by measuring epithelial height in proportion to thickness of the lamina propria (epithelium-lamina propria ratio). Tissue oxygenation was determined using a fluorescence quenching technique, and graft perfusion monitoring was performed by laser Doppler flowmetry and lectin-binding assay. Immunohistochemistry was used for detection of CD31 and inducible nitric oxide synthase while iron deposition was shown with Prussian blue reaction. Quantitative reverse transcription polymerase chain reaction analysis was used for gene expression analysis. RESULTS: Isografts maintained good oxygenation and perfusion throughout the experiment, while both were drastically reduced in allografts. Treatment with clopidogrel attenuated graft hypoxia and reduced loss of perfusion. Additionally, clopidogrel led to increased epithelium-lamina propria ratio while iron deposition was impaired. Gene expression analysis revealed elevated levels of angiogenic vascular endothelial growth factor in the clopidogrel group. Improved endothelial function was shown by immunohistochemistry (CD31, inducible nitric oxide synthase). CONCLUSIONS: Continuous administration of clopidogrel significantly improved tissue oxygenation, limited microvascular leakiness, and prevented airway ischemia. These data demonstrate that clopidogrel ameliorates microvascular injury during acute airway rejection, which is a known predisposing factor for the development of CLAD.
Authors with CRIS profile
Christian Heim
Department of Cardiac Surgery
Martina Ramsperger-Gleixner
Department of Cardiac Surgery
Michael Weyand
Lehrstuhl für Herzchirurgie
Involved external institutions
VA Palo Alto Health Care System
United States (USA) (US)
Universitätsklinikum Schleswig-Holstein (UKSH)
Germany (DE)
Universitätsklinikum Ulm
Germany (DE)
United States (USA) (US)
Universitätsklinikum Schleswig-Holstein (UKSH)
Germany (DE)
Universitätsklinikum Ulm
Germany (DE)
How to cite
APA:
Heim, C., Khan, M.A., von Silva-Tarouca, B., Kuckhahn, A., Stamminger, T., Ramsperger-Gleixner, M.,... Ensminger, S.M. (2019). Preservation of Microvascular Integrity in Murine Orthotopic Tracheal Allografts by Clopidogrel. Transplantation, 103(5), 899-908. https://dx.doi.org/10.1097/TP.0000000000002571
MLA:
Heim, Christian, et al. "Preservation of Microvascular Integrity in Murine Orthotopic Tracheal Allografts by Clopidogrel." Transplantation 103.5 (2019): 899-908.
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