Accession Number : ADA296823

Title :   Pathogenesis of Septic Acute Lung Injury and Strategies for Immuno-Pharmacological Therapy.

Descriptive Note : Rept. for 1 May 93-30 Apr 95,

Corporate Author : VIRGINIA COMMONWEALTH UNIV RICHMOND

Personal Author(s) : Sugerman, Harvey J. ; Fowler, Alpha A., III

PDF Url : ADA296823

Report Date : 30 MAY 1995

Pagination or Media Count : 69

Abstract : During the report period, we studied sepsis-associated acute lung injury using a porcine model. In multiple protocols we found that deletion of certain proinflammatory mediators or disruption of neutrophil - endothelial cellular adhesion molecules effectively attenuate lung injury. Pentoxifylline exerts significant beneficial effects on pulmonary and systemic hemodynamics1 however, if administration is delayed until established septic shock, the agent may exacerbate systemic hypotension. A synthetic lipid A analog, B464, provided significant, yet incomplete, protection against cardiovascular and pulmonary derangements. Bradykinin antagonist, NPC1773, protected against sepsis-induced lung injury and attenuated the intensity of septic shock. An antibody to both E-selectin and L-selectin failed to protect against septic shock, while affording significant protection against sepsis-induced lung injury. Sialylated oligosaccharides, a ligand for selectin interactions, afforded significant protection against the development of lung injury, but did not attenuate hemodynamic derangements. Each pathway or biochemical system examined exerts important biological effects at unpredictable points following the onset of systemic inflammation. A critical feature common to all therapies studied, is the increasing loss of efficacy as treatments are delayed. This underscores the need for a biochemical Mmarker of vascular injury, which will facilitate optimal timing of interventional therapies.

Descriptors :   *LUNG, *WOUNDS AND INJURIES, *RESPONSE(BIOLOGY), *ACUTE RESPIRATORY DISEASE VIRUS, MODELS, MOLECULES, CELLS, BIOCHEMISTRY, LIPIDS, ADHESION, INTENSITY, THERAPY, POISONING, LOSSES, INFLAMMATION, CARDIOVASCULAR SYSTEM, PATHOGENESIS, SHOCK(PATHOLOGY), MICROORGANISMS, ENDOTHELIUM, SWINE, HYPOTENSION.

Subject Categories : Anatomy and Physiology
      Ecology

Distribution Statement : APPROVED FOR PUBLIC RELEASE