Targeted fibre-optical intrabronchial lipopolysaccharide administration in pigs – a methodical refinement for improved accuracy in respiratory research. (January 2021)

• Record Type: Journal Article
• Authors: Ruemmler, Robert; Ziebart, Alexander; Britten, Elisabeth; Kamuf, Jens; Garcia-Bardon, Andreas; Hartmann, Erik Kristoffer
• Is Part Of: Veterinary anaesthesia and analgesia. Volume 48:Number 1(2021)
• Page Start: 26
• Page End: 34
• Publication Date: 2021-01
• Subjects: ARDS -- fibre-optic endoscopy -- LPS -- porcine -- targeted application; Veterinary anesthesia -- Periodicals; 636.089
• DOI: 10.1016/j.vaa.2020.08.008
• Languages: English
• ISSNs: 1467-2987

Abstract

Abstract: Objective: To establish and evaluate a standardized method of targeted, intrabronchial drug delivery in pigs. Study design: Randomized controlled trial. Animals: A total of 16 German Landrace pigs ( Sus scrofa ), age range 12‒16 weeks, and weighing 28‒35 kg. Methods: The animals were anaesthetized, intubated, and instrumented with extended cardiovascular monitoring. Lung injury was induced by administering via a flexible fibre-optic endoscope using 100 mL saline solution containing either 20 mg of Escherichia coli lipopolysaccharide ( E. coli LPS) ( n = 8) or no additive (sham, n = 8) into the two distal mainstem bronchi. The animals were monitored for 8 hours and arterial oxygenation, inspiratory pressure and arterial blood pressure were measured repeatedly. Post-mortem, lung tissue was prepared for histologic damage scoring and determination of proinflammatory cytokines Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). Statistical analyses were performed using inter-group analysis of variance and Student's t tests. Data are presented as mean ± standard deviation. A p value <0.05 was considered significant. Results: The targeted application of LPS led to significant deterioration of oxygenation consistent with mild-to-moderate acute respiratory distress syndrome (ARDS) and hypotension (Horowitz ratio: sham 2 hour, 300 ± 39; LPS 2 hour, 193.7 ± 52; p < 0.001). Histologic analyses identified increased inflammation and oedema in the tissues of the animals in the LPS group IL-6 sham: 6.4 ± 4.4 × 10 –5 pg mL –1 ; IL-6 LPS : 2.8 ± 2.4 × 10 –4 pg mL –1, p = 0.015. Conclusions: The targeted application of agents via flexible fibre-optic endoscopy is a valid, reliable method of causing controlled lung damage in a porcine model. The data presented suggest the feasibility and possible advantages of controlled application and could expand the array of techniques used to help understand the critical condition of ARDS. In addition, a targeted approach could help reduce animal numbers used for this purpose.