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; Sharar, SR; Harlan, JM; Tedder, TF; Winn, RK
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