Pressure delivery of AS-ICAM-1 ODN with LFA-1 mAb reduces reperfusion injury in cardiac allografts.

Abstract

BACKGROUND:

The goal of this study is to determine the effects of ex vivo hyperbaric pressure administration of AS-ICAM-1 ODN and systemic anti-LFA-1 mAb treatment on reperfusion injury in the rat cardiac allograft model.

METHODS:

A PVG to ACI functional heterotopic rat heart model was used. Donor hearts were treated with either saline or AS-ICAM-1 ODN and 5 atm of hyperbaric pressure for 45 minutes. Anti-LFA-1 mAb was administered systemically prior to reperfusion of the allograft. Allografts were procured 24 hours after transplantation for assessment of reperfusion injury or 72 hours to determine ICAM-1 protein expression.

RESULTS:

Ex vivo administration of AS-ICAM-1 ODN led to decreases in percentage wet weight (77.1+/-0.83% vs 78.7+/-1.0%, p < 0.05), myeloperoxidase activity (3.14+/-0.72 vs 4.07+/-0.59, p < 0.05), contraction band necrosis (6.4+/-6.47% vs 21.1+/-7.43%, p < 0.01), and ICAM-1 protein expression determined by immunohistochemistry compared to saline controls. Treatment with anti-LFA-1 mAb resulted in decreases in wet weight ratio (76.7+/-0.63%, p < 0.05 vs saline), myeloperoxidase activity (3.58+/-0.39, p < 0.05 vs saline) and contraction band necrosis (11.8+/-3.56%, p < 0.05 vs saline). Combination of pressure administration of AS-ICAM-1 ODN and anti-LFA-1 mAb decreased wet weight ratios (77.1+/-0.93%, p < 0.05 vs saline), myeloperoxidase activity (2.88+/-0.44, p < 0.01 vs saline), and contraction band necrosis (6.75+/-5.67%, p < 0.05 vs saline).

CONCLUSIONS:

Ex vivo pressure mediated delivery of AS-ICAM-1 ODN decreases ICAM-1 protein expression, reduces reperfusion injury in rodent cardiac allografts, and is more effective than anti-LFA-1 mAb treatment alone.

• Authors: B T Feeley, A K Park, S Alexopoulos, E G Hoyt, M P Ennen, R S Poston Jr, R C Robbins
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 68 Issue 1 Pg. 119-24 (Jul 1999) ISSN: 0003-4975 [Print] Netherlands
• PMID: 10421126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AS-ICAM-1 ODN
• Antibodies, Monoclonal
• Lymphocyte Function-Associated Antigen-1
• Oligodeoxyribonucleotides
• Oligodeoxyribonucleotides, Antisense
• Intercellular Adhesion Molecule-1
• Peroxidase

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• Atmospheric Pressure
• Heart Transplantation
• Intercellular Adhesion Molecule-1 (analysis)
• Lymphocyte Function-Associated Antigen-1 (immunology)
• Male
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocardium (metabolism, pathology)
• Necrosis
• Oligodeoxyribonucleotides
• Oligodeoxyribonucleotides, Antisense (administration & dosage)
• Peroxidase (metabolism)
• Rats
• Rats, Inbred ACI
• Rats, Inbred Strains
• Transplantation, Heterotopic