Bosutinib reduces endothelial permeability and organ failure in a rat polytrauma transfusion model

• DOI: 10.1016/j.bja.2021.01.032
• Publication Date: 2021-03-06T20:09:09Z
• Authors: Derek J.B. Kleinveld; Liza Botros; M. Adrie W. Maas; Jesper Kers; Jurjan Aman; Markus W. Hollmann; Nicole P. Juffermans
• Keywords: Polytrauma; Bosutinib

BackgroundTrauma-induced shock is associated with endothelial dysfunction. We examined whether the tyrosine kinase inhibitor bosutinib as an adjunct therapy to a balanced blood component resuscitation strategy reduces trauma-induced permeability, thereby improving reversal and limiting transfusion requirements organ failure in rat polytrauma model.MethodsMale Sprague–Dawley rats (n=13 per group) were traumatised exsanguinated until MAP of 40 mm Hg was reached, then randomised two groups: red cells, plasma platelets 1:1:1 ratio either or vehicle. Controls sham (median laparotomy, no trauma) Organs harvested for histology wet/dry (W/D) weight ratio.ResultsTraumatic injury resulted shock, higher lactate levels compared controls. In volume needed obtain 60 lower bosutinib-treated animals (2.8 [2.7–3.2] ml kg−1) vehicle (6.1 [5.1–7.2] kg−1, P<0.001). Lactate group 2.9 [1.7–4.8] mM 6.2 [3.1–14.1] (P=0.06). Bosutinib reduced lung vascular leakage (W/D 5.1 [4.6–5.3] vs 5.7 [5.4–6.0] (P=0.046) scores (P=0.027).ConclusionsBosutinib volume, improved reversal, leak model.