Effect of a vascular endothelial cadherin antagonist in a rat lung transplant model.

Abstract

BACKGROUND:

Adherens junctions are critically important in control of endothelial cell permeability. Bβ15-42 is a peptide product of fibrin degradation that binds to vascular endothelial cadherin, the major component of endothelial adherens junctions. We tested the hypothesis that Bβ15-42 improves lung function in our rat lung transplant model.

METHODS:

Bβ15-42 was administered to donors before lung retrieval and to recipients by continuous intravenous infusion, or just to recipients, or neither. Recipients were monitored, anesthetized and ventilated, for 6 hours. Outcome measures were indices of lung function (edema [wet-to-dry weight ratio], oxygenation, dynamic compliance) and bronchoalveolar fluid measures of inflammation (protein, cell count, differential, and cytokines).

RESULTS:

Bβ15-42 therapy was associated with improved graft lung function, including less edema, and improved oxygenation and airway pressure, particularly if Bβ15-42 was administered to both the donor and recipient. However, Bβ15-42 had little or no effect on bronchoalveolar fluid measures of inflammation. Analysis of bronchoalveolar fluid protein concentration showed Bβ15-42 may enhance alveolar fluid clearance.

CONCLUSIONS:

Bβ15-42 may be a useful therapy to reduce edema and improve graft function after lung transplant, alone or as an adjunct to other therapies.

• Authors: Zhigang Tian, Boming Dong, John W Blackwell, Paul W Stewart, Thomas M Egan
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 95 Issue 3 Pg. 1028-33 (Mar 2013) ISSN: 1552-6259 [Electronic] Netherlands
• PMID: 23333062 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• Cadherins
• Cytokines
• Fibrin Fibrinogen Degradation Products
• Peptide Fragments
• cadherin 5
• fibrinogen Bbeta (15-42)

Topics

• Adherens Junctions (metabolism)
• Animals
• Antigens, CD (metabolism)
• Bronchoalveolar Lavage Fluid (chemistry)
• Cadherins (antagonists & inhibitors, metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Fibrin Fibrinogen Degradation Products (administration & dosage, pharmacokinetics)
• Graft Rejection (metabolism, physiopathology, prevention & control)
• Infusions, Intravenous
• Lung (blood supply, drug effects, metabolism, physiopathology)
• Lung Transplantation
• Male
• Peptide Fragments (administration & dosage, pharmacokinetics)
• Pulmonary Gas Exchange (drug effects)
• Rats
• Rats, Sprague-Dawley