Anti-CD11b monoclonal antibody improves myocardial function after six hours of hypothermic storage.
BACKGROUND
The shortage of pediatric heart donors often necessitates considerable travel time and, as a result, prolonged donor heart ischemia. This excessive hypothermic storage may contribute markedly to myocardial dysfunction in the recipient.


METHODS
We investigated the role of leukocyte-endothelial interactions in this dysfunction in an isolated, immature (mean age, 11.8 +/- 1.6 days) swine heart model using a monoclonal antibody against a leukocyte adhesion molecule. We studied a total of 20 hearts subjected to 6 hours of cardioplegic arrest at 4 degrees C. Group M1/70 (n = 6) received at reperfusion 15 micrograms/mL of a monoclonal antibody F(ab')2 fragment to CD11b, the alpha-subunit of the leukocyte adhesion molecule Mac-1. Group MB10.6 (n = 8) received 15 micrograms/mL of the swine unreactive F(ab')2 MB10.6, and the third group received saline vehicle.


RESULTS
Administration of M1/70 resulted in improved postischemic recovery of ventricular function compared with the two control groups (p < 0.05).


CONCLUSIONS
These data implicate leukocyte-endothelial interactions mediated by the leukocyte adhesion molecule CD11b in myocardial dysfunction after long-term hypothermic ischemia. Specific antiadhesion strategies such as this may safely extend storage time for pediatric donor hearts.
Department of Cardiovascular Surgery, Children's Hospital, Boston, MA 02115, USA.
J M
JM
Forbess
T
T
Hiramatsu
F
F
Nomura
T
T
Miura
G K
GK
Farrington
K
K
Sokolowski
M
M
Bree
J E
JE
Mayer
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D015925:Cryopreservation / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D016027:Heart Transplantation; D016177:Macrophage-1 Antigen / Q000276:immunology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009926:Organ Preservation / Q000379:methods*; D013552:Swine; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects
D000911:Antibodies, Monoclonal; D002314:Cardioplegic Solutions; D016177:Macrophage-1 Antigen