Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates.
Neutrophil adherence or aggregation may be important in the development of organ injury after hemorrhagic shock. Monoclonal antibody (MAb) 60.3 prevents both adherence and aggregation. Therefore we investigated MAb 60.3 treatment in prevention of organ injury after hemorrhagic shock in rhesus monkeys (Macaca mulatta). We performed esophagogastroscopy and placed catheters to measure cardiac output, mean arterial pressure, arterial blood gases, and urine output. Blood was removed to decrease CO to 30% of baseline for 90 minutes. Just before resuscitation, MAb 60.3 (2 mg/kg) or saline solution (control) was administered intravenously. Monitoring and fluid resuscitation continued for 24 hours, with lactated Ringer's solution given as a maintenance infusion (4 ml/kg/hr) plus additional lactated Ringer's solution to maintain CO at preshock levels. Esophagogastroscopy was repeated 24 hours after shock. There were two deaths in the control group at about 72 hours and none in the MAb 60.3 group. MAb 60.3-treated animals required less fluid (9.6 +/- 8.8 ml/kg vs 263.8 +/- 225.7 ml/kg), gained less weight (0.08 +/- 0.11 kg vs 0.70 +/- 0.37 kg), and maintained a higher hematocrit level (35.0% +/- 1.0% vs 26.9% +/- 4.9%). All five control animals had gastritis; MAb 60.3-treated animals had none (p less than 0.05; Fisher's exact test). Inhibition of neutrophil adherence or aggregation with MAb 60.3 at the time of resuscitation reduces fluid requirements and gastric injury in monkeys after hemorrhagic shock.
Mileski
W J
WJ
Department of Surgery, University of Washington School of Medicine, Seattle.
Winn
R K
RK
Vedder
N B
NB
Pohlman
T H
TH
Harlan
J M
JM
Rice
C L
CL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D001158:Arteries; D001772:Blood Cell Count; D018821:CD18 Antigens; D002302:Cardiac Output; D002448:Cell Adhesion / Q000187:drug effects; D005440:Fluid Therapy; D005756:Gastritis / Q000209:etiology; D008253:Macaca mulatta; D009102:Multiple Organ Failure / Q000276:immunology / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000473:pathology / Q000628:therapy
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D010100:Oxygen