Blocking l-selectin function attenuates reperfusion injury
following hemorrhagic shock in rabbits.
Ramamoorthy, Chandra, Sam R. Sharar, John M. Harlan, Thomas F. Tedder,
Robert K. Winn.
Departments of Anesthesiology, Medicine, Surgery, University of
Washington, Harborview Medical Center, Seattle, WA 98104 and
Department of Immunology, Duke University Medical Center, Durham, NC
27706
APStracts 3:0113H, 1996.
Leukocyte adhesion molecule blockade reduces ischemia-reperfusion
injury. We tested the hypothesis that a monoclonal antibody (MAb)
which recognizes a functional epitope of L-selectin would decrease
hemorrhagic shock-induced reperfusion injury. Anesthetized rabbits
were subjected to two hours of hemorrhagic shock (cardiac output
reduced to 30% of baseline) then given MAbs that recognize functional
domains of L-selectin (LAM1-3) or CD18 (60.3), or one that recognizes
a non-functional domain on L-selectin, (LAM1-14), or saline
immediately prior to resuscitation with shed blood. Additional fluids
were administered as needed to maintain cardiac output at baseline
levels for six hours. 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 was
significantly less than saline-treated controls (142 +/- 142 ml/kg).
However, two animals treated with MAb LAM1-14 died prior to six
hours. If their resuscitation volumes are projected to six hours by
linear regression, 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.
Received 19 October 1995; accepted in final form 6 March 1996.
APS Manuscript Number H975-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96