Inhibition of leukocyte adherence in a rabbit model of major thermal injury.
Leukocytes and the process of leukocyte adherence have been implicated in the pathogenesis of organ dysfunction after ischemic injury and inflammation. We asked the question: Will inhibition of leukocyte adherence by administration of a monoclonal antibody to intercellular adhesion molecule alter the systemic response to major thermal injury? New Zealand white rabbits instrumented to measure mean arterial pressure, cardiac output, urine output, and arterial oxygenation were deeply anesthetized, and 30% total body surface area full-thickness burn was created by applying brass probes heated to 100 degrees C to the animals' backs for 15 seconds. The animals were continuously monitored, resuscitated, and given analgesic for 24 hours. There were three experimental groups: I-controls (n = 7), anesthetized and monitored; II-30% burn (n = 7) given 30% total body surface area + vehicle (saline solution 1.0 ml/kg every 8 hours); III-30% burn + R6.5 (n = 6) animals given a monoclonal antibody (R6.5, 2.0 mg/kg every 8 hours) directed against the intercellular adhesion molecule beginning 30 minutes after burn. This model of a 30% total body surface area burn injury resulted in hypotension and hypoxemia in the burn group. The animals given the antibody R6.5 maintained higher mean arterial pressure and arterial oxygenation at several points. These results suggest that leukocytes and leukocyte adherence may be involved in the pathogenesis of the systemic sequellae of major thermal injury.
Mileski
W
W
Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9031.
Gates
B
B
Sigman
A
A
Sikes
P
P
Atiles
L
L
Lightfoot
E
E
Lipsky
P
P
Baxter
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D002056:Burns / Q000150:complications / Q000276:immunology / Q000628:therapy*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D007022:Hypotension / Q000517:prevention & control; D000860:Hypoxia / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1