Pressure delivery of AS-ICAM-1 ODN with LFA-1 mAb reduces reperfusion injury in cardiac allografts.
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.
Department of Cardiothoracic Surgery, Stanford University Medical Center, California 94305-5407, USA.
B T
BT
Feeley
A K
AK
Park
S
S
Alexopoulos
E G
EG
Hoyt
M P
MP
Ennen
R S
RS
Poston
R C
RC
Robbins
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001274:Atmospheric Pressure; D016027:Heart Transplantation; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D016042:Transplantation, Heterotopic
C120298:AS-ICAM-1 ODN; D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase