Prevention of acute lung injury in swine: depletion of pulmonary intravascular macrophages using liposomal clodronate.

Journal Article

BACKGROUND: Swine contain large numbers of pulmonary intravascular macrophages (PIMs) that mediate the physiological response observed in acute lung injury (ALI). As the hyperacute dysfunction observed in pulmonary xenotransplantation is similar to endotoxin-induced ALI, PIMs may play a critical role in pulmonary xenograft dysfunction. We used liposomal clodronate to eliminate the PIM population in a model of acute swine lung injury. MATERIALS AND METHODS: Experimental swine (n = 6) received liposomal clodronate (1.25 g/10 kg) and control swine (n = 5) received saline containing liposomes before infusion of lipopolysaccharide (450 ng/kg). RESULTS: Control swine demonstrated higher peak pulmonary artery pressures (41.8 +/- 2.2 versus 16.8 +/- 1.2 mm Hg; P < 0.0001) and higher peak pulmonary vascular resistances (1405 +/- 209 versus 353 +/- 81 dynes. s. cm(-5); P = 0.0016) in response to lipopolysaccharide infusion. Clodronate treated swine also had significantly lower serum levels of tumor necrosis factor-alpha, interleukin-6, and thrombin. CONCLUSIONS: Liposomal clodronate effectively attenuates acute swine lung injury induced by endotoxin. This method of depletion of the PIM population presents a promising new treatment of swine lungs before xenotransplantation.

Full Text

Duke Authors

Cited Authors

  • Gaca, JG; Palestrant, D; Lukes, DJ; Olausson, M; Parker, W; Davis, RD

Published Date

  • June 1, 2003

Published In

Volume / Issue

  • 112 / 1

Start / End Page

  • 19 - 25

PubMed ID

  • 12873428

International Standard Serial Number (ISSN)

  • 0022-4804

Language

  • eng

Conference Location

  • United States