Blocking L-selectin function attenuates reperfusion injury following hemorrhagic shock in rabbits.
Leukocyte adhesion molecule (LAM) blockade reduces ischemia-reperfusion injury. We tested the hypothesis that a monoclonal antibody (MAb) that recognizes a functional epitope of L-selectin would decrease hemorrhagic shock-induced reperfusion injury. Anesthetized rabbits were subjected to 2 h of hemorrhagic shock (cardiac output reduced to 30% of baseline), then given one of the following treatments: MAbs that recognize functional domains of L-selectin (LAM1-3), CD18 (60.3), MAbs that recognize a nonfunctional domain on L-selectin (LAM1-14), or saline, immediately before resuscitation with shed blood. Additional fluids were administered as needed to maintain cardiac output at baseline levels for 6 h. The cumulative fluid resuscitation after MAb LAM1-3 (58 +/- 34 ml/kg) was not significantly different from after MAb 60.3 (21 +/- 24 ml/kg) or MAb LAM1-14 (66 +/- 51 ml/kg), but it was significantly less than saline-treated controls (142 +/- 142 ml/kg). However, two animals treated with MAb LAM1-14 died before 6 h. If their resuscitation volumes are projected to 6 h by linear regression, then the LAM1-14-treated group required significantly greater volume (101 +/- 99 ml/kg) than the MAb LAM1-3-treated group. We conclude that MAbs to a functional domain on L-selectin are protective against reperfusion-injury following hemorrhagic shock.
Ramamoorthy
C
C
Department of Anesthesiology, University of Washington, Harborview Medical Center, Seattle 98104, USA.
Sharar
S R
SR
Harlan
J M
JM
Tedder
T F
TF
Winn
R K
RK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001158:Arteries; D005440:Fluid Therapy; D005740:Gases / Q000097:blood; D006439:Hemodynamics; D007511:Ischemia / Q000209:etiology*; D019041:L-Selectin / Q000276:immunology*; D007958:Leukocyte Count; D009504:Neutrophils / Q000166:cytology; D011817:Rabbits; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000628:therapy
D000911:Antibodies, Monoclonal; D005740:Gases; D019041:L-Selectin