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Right arrow Transplantation - heart

Ann Thorac Surg 2002;74:2064-2070
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

Intracoronary E-/L-selectin blockade reduces neutrophil infiltration in heart transplantation

Yvonne M. Carter, MDa, Robert Thomas, BSa, Robert Bargatze, PhDc, Veronica Poppa, MSb, Mark Jutila, PhDd, Charles E. Murry, MD, PhDb, Margaret D. Allen, MDe*

a Department of Surgery, University of Washington, Seattle, Washington, USA
b Department of Pathology, University of Washington, Seattle, Washington, USA
c Ligocyte Pharmaceuticals, Inc, Bozeman, Montana, USA
d Veterinary Molecular Biology Laboratory, Montana State University, Bozeman, Montana, USA
e Hope Heart Institute, Seattle, Washington, USA

Accepted for publication July 15, 2002.

* Address reprint requests to Dr Allen, The Hope Heart Institute, 1710 E. Jefferson St, Seattle WA 98122, USA.
e-mail: mallen{at}hopeheart.org

BACKGROUND: This study examined the effect of local intracoronary delivery of a unique monoclonal antibody (mAb) to both E- and L-selectin (EL-246) on neutrophil infiltration after global ischemia during cardiac transplantation.

METHODS: In 12 ovine heart transplants, allograft coronary arteries were locally perfused with EL-246 (n = 6), or isotype-matched control antibodies (n = 2) or saline (n = 4). At 24 hours posttransplant, myocardium was analyzed for neutrophil infiltration and myocardial water content.

RESULTS: The mean number of intramyocardial neutrophils per area (PMN/hpf) was greatly reduced in the allografts perfused with EL-246 (3.45 ± 0.4 PMN/hpf), compared with an average 6.5 ± 0.97 PMN/hpf in control hearts (p = 0.004). Peripheral leukocyte counts were unaffected; myocardial water content was not significantly reduced.

CONCLUSIONS: Local perfusion of cardiac allografts with blocking antibody EL-246 before reperfusion significantly reduced the neutrophilic infiltration that occurs early after transplantation. Prohibiting neutrophil–endothelial adhesion and transmigration may be useful in decreasing neutrophil-dependent post-reperfusion injury in transplantation and routine cardiac surgery.






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Copyright © 2002 by The Society of Thoracic Surgeons.