Vascular Endothelial-Cadherin Expression After Reperfusion Correlates With Lung Injury in Rat Lung Transplantation

Ann Thorac Surg. 2016 Jun;101(6):2161-7. doi: 10.1016/j.athoracsur.2016.01.040. Epub 2016 Apr 13.

Abstract

Background: Vascular endothelial-cadherin (VEC), composing the adherens junction of endothelial cells, has been shown to regulate vascular permeability. The aim of this study was to investigate VEC expression during cold ischemia (CI) and reperfusion and whether a dibutyryl cyclic adenosine 3',5'-monophosphate (db-cAMP) and nitroglycerin (NTG) additive to preservation solution can maintain VEC.

Methods: Rat left lung transplantation after CI was performed, and reperfusion was done for 2 hours. The experimental groups were Control (n = 5), CI3 (n = 5), CI6 (n = 6), and CI6+AMP/NTG (n = 6) with minimum ischemic period, 3 hours and 6 hours of CI, respectively, and 6 hours of CI with db-cAMP and NTG additive to preservation solution, respectively. Lung mechanics, lung wet-to-dry weight ratio (W/D), and the histologic findings of the graft were evaluated. The expression of VEC was evaluated by Western blot analysis of the lung tissue lysates.

Results: The CI3 group showed a decrease in dynamic compliance with perivascular edema. Dynamic compliance, graft oxygenation, and W/D were substantially deteriorated, and intraalveolar edema with neutrophil infiltration was recognized in the CI6 group. They were improved in the CI6+AMP/NTG group. VEC expression was maintained during CI. After reperfusion, it reduced substantially in the CI6 group and was maintained in the CI6+AMP/NTG group.

Conclusions: VEC expression was maintained during CI; however, it reduced early after reperfusion after 6 hours of CI, correlating with severe intraalveolar edema. db-cAMP/NTG additive to the preservation solution contributed to the maintenance of VEC expression after reperfusion.

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / pathology*
  • Animals
  • Antigens, CD / analysis*
  • Biopsy, Needle
  • Blotting, Western
  • Cadherins / analysis*
  • Disease Models, Animal
  • Graft Rejection
  • Graft Survival
  • Immunohistochemistry
  • Lung Transplantation / adverse effects*
  • Lung Transplantation / methods
  • Organ Preservation / methods*
  • Organ Preservation Solutions / pharmacology
  • Random Allocation
  • Rats
  • Reference Values
  • Reperfusion / methods
  • Reperfusion Injury / pathology*
  • Reperfusion Injury / prevention & control

Substances

  • Antigens, CD
  • Cadherins
  • Organ Preservation Solutions
  • cadherin 5