Targeted fibre-optical intrabronchial lipopolysaccharide administration in pigs – a methodical refinement for improved accuracy in respiratory research

Intrabronchial Application of Extracellular Histones Shows No Proinflammatory Effects in Swine in a Translational Pilot Study

“…Although the intrabronchially instilled animals showed a signi cant decrease in gas exchange and oxygenation, these results were expected and most likely due to the uid congesting and compromising the lung. However, no additional impairments were observed beyond the initial drop in PaO 2, although previous experiments by our group showed signi cantly increased in ammation when the same protocol was used with lipopolysaccharide instillation (10) . While histones have been described to be toxic to epithelial and endothelial cells in vitro (2,5) , no speci c in ammatory changes were detected in either of the lung damage groups.…”

“…Additionally, we designed a standardized acute lung injury model for lipopolysaccharides using the same methods. This report has already been published elsewhere (10) . We hypothesized that overdoses of histones should have comparable effects in swine and would cause tissue in ammation and alveolar leakage in the lung as well as septic organ damage when injected into the bloodstream.…”

“…Second, the instillation method could be criticized as awed with a high potential of confounding factors due to relatively high instillation volumes and signi cantly decreased pulmonary function in both the sham and histone groups, most likely due to intra-alveolar edema and atelectasis. However, in another trial of our group, the exact same method was used with comparable initial declines in PaO 2 after instillation of 20 mg lipopolysaccharide (LPS), and we could still detect signi cant increases in tissue in ammation as well as septic circulatory effects (10) . LPS and histones should affect similar pathways, heavily relying on Toll-like receptors 2 and 4 (2,4) .…”

“…Twenty male German landrace pigs (12-16 weeks, 28-35 kg) were acquired from a local private farm and were treated as described previously (10,11) .…”

“…Histone iv 68( 10) 76( 13) 76( 16) 74( 13) 73( 9) 66( 7 9) 54( 9) 54( 16) 55( 6) 50 (10) [%] Histone it 67( 8) 50( 13) 53( 13) 60( 10) 56( 9) 52( 9)…”