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Ann Thorac Surg 1999;68:119-124
© 1999 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, California, USA
Address reprint requests to Dr Robbins, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305-5407
e-mail: robbins{at}leland.stanford.edu
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.
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