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Anti-CD11b monoclonal antibody improves myocardial function after six hours of hypothermic storage
J M Forbess1, T Hiramatsu, F Nomura
1Department of Cardiovascular Surgery, Children's Hospital, Boston, MA 02115, USA.
Insights
Targeting leukocyte adhesion molecule CD11b improved recovery of infant donor hearts after prolonged cold storage. This strategy may help extend preservation times, benefiting pediatric heart transplantation.
Area of Science:
- Cardiology
- Immunology
- Transplantation Science
Background:
- Pediatric heart donor shortage leads to extended organ ischemia due to travel.
- Prolonged hypothermic storage of donor hearts can cause myocardial dysfunction in recipients.
Purpose of the Study:
- To investigate the role of leukocyte-endothelial interactions in myocardial dysfunction after prolonged ischemia.
- To evaluate the efficacy of targeting the CD11b adhesion molecule in a pediatric swine heart model.
Main Methods:
- Used an isolated, immature swine heart model subjected to 6 hours of hypothermic cardioplegic arrest.
- Administered a monoclonal antibody fragment (M1/70) targeting CD11b at reperfusion in one group.
- Compared outcomes with control groups receiving an unreactive antibody or saline vehicle.
Main Results:
- The M1/70 antibody significantly improved postischemic recovery of ventricular function compared to controls (p < 0.05).
- This suggests CD11b-mediated leukocyte-endothelial interactions contribute to heart dysfunction.
Conclusions:
- Leukocyte-endothelial interactions via CD11b play a role in myocardial dysfunction following extended hypothermic ischemia.
- Targeted antiadhesion therapies may offer a safe method to extend donor heart preservation for pediatric transplants.
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.