Vessel markers like ephrinB2 and ephB4 could be suitable markers for perfusion direction and acute lung injury

Abstract

Rationale: Retrograde lung vascular perfusion can appear in high risk surgeries. This study is the first to study long term retrograde perfusion of isolated perfused mouse lungs (IPL) and to investigate the tyrosine kinase ephB4 and its ligand ephrinB2 as a potential markers for acute lung injury. Methods: Mouse lungs were subjected to anterograde or retrograde perfusion with normal pressure ventilation (NV) or high pressure ventilation (=overventilation, OV) for 4h. Outcome parameters were cytokine, ephrinB2 and ephB4 levels in perfusate samples and bronchoalveolar lavage (BAL), and the wet-to-dry ratio. BAL levels of ephrinB2 and ephB4 were also determined in vivo, including mice ventilated for 7h with normal volume (NVV) or high volume (HVV). Results: Retrograde perfusion resulted in an increased wet-to-dry ratio when combined with OV; other physiological parameters were not affected. Cytokine levels in BAL and perfusate, as well as levels of soluble ephB4 in BAL were increased in OV, while soluble ephrinB2 BAL levels were increased in retrograde perfusion. BAL levels of ephB4 were also increased in vivo in mice ventilated for 7h with HVV. Conclusions: Retrograde perfusion has an influence on pulmonary oedema formation when combined with ventilation-induced barotrauma. EphrinB2 seems to be upregulated by flow reversal. EphB4 could be a promising marker in BAL for acute lung injury ex vivo and in vivo.