Transient inhibition of CD18-dependent leukocyte functions after hemorrhage and polymicrobial sepsis

S. P. Lyden, J. H. Patton, N. Ragsdale, M. A. Croce, T. C. Fabian, K. G. Proctor

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11 Scopus citations

Abstract

Background. The goals were (1) to characterized physiologic changes after a combined insult of hemorrhage plus sepsis in a large animal model and (2) to determine whether transient inhibition of the nuetorphil CD18 adherence receptor during fluid resuscitation impairs host defense during recovery from this injury. Methods. Two series of experiments were performed in anesthized swine. In the first series (n = 22), the cecum was ligated and incised immediately before 35% hemorrhage. After 1 hour, shed blood plus supplemental fluid was administered to restore and stabilized hemodynamics. On the basis of these results, a second series examined effects of anti-CD 18 (2 mg/kg R15.7; n =9) or its saline placebo (n = 10) administered during fluid resuscitation. Results. In the first series the mortality rate was 41% of (9 of 22). Early deaths occurred 3.0 ± 0.8 days after injury and were distinguished by significantly lower neutrophil counts on resuscitation. Those alive at 7 days had intraabdominal abscesses and bacteremia. Alveoli and peribronchial spaces were congested, with edema and fibrin disposition in capillaries and alveoli. Livers were congested with biliary stasis. Despite these pathologic findings, hemodynamic, electrolyte, and serum enzyme changes were minimal. In the second series of mortality rate of 4 days was 30% with placebo (3 of 10) versus 33% with anti-CD18 (3 of 9). Lung changes (i.e., pneumonia, pleuritis, thrombosis, and edema) were similar in both groups, but liver congestion and hemorrhage were attenuated by anti-CD18. Some aspects of host defense were altered by anti-CD18. At 24 and 48 hours the oxidative burst potential for circulating granulocytes was 208% ± 57% and 383 ± 73% with placebo versus 1273% ± 351% and 762% ± 226% in anti CD18. At 72 hours the granularity of circulating neutrophils was unchanged form baseline with placebo was reduced to 82% ± 5% by anti-CDs. At 48 hours lipopolysaccharide- evoked tumor necrosis factor production in vitro was reduced to 62% ± 22% with placebo but was increased to 148% 16% with anti-CD18. Conclusions. Anti- CD18 during fluid resuscitation did not increase vulnerability to endogenous pathogen because the transient inhibition of neutrophil demargination was balanced by enhanced oxidative burst, degranulatio, and production of tumor necrosis factor in circulating cells later during recovery. Thus a single administration of antiadhesion therapy does not worsen posttrauma outcome even if given during ongoing sepsis.

Original languageEnglish (US)
Pages (from-to)679-691
Number of pages13
JournalSurgery
Volume123
Issue number6
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery

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