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Ann Thorac Surg 1999;68:119-124
© 1999 The Society of Thoracic Surgeons


Original Articles

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

Brian T. Feeley, BSa, Aric K. Park, BSa, Sophoclis Alexopoulos, BSa, E. Grant Hoyta, Michael P. Ennen, BSa, Robert S. Poston, Jr, MDa, Robert C. Robbins, MDa

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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