Transfusion-associated effects of extra-cellular hemoglobin on development and severity of ventilator-induced lung injury

• Applicant: Professor Dr. Jan Adriaan Graw
• Subject Area: Anaesthesiology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 420420493

Our work is focused on the combined adverse effects of ventilator-induced lung injury (VILI) and blood transfusions. Recently, we demonstrated that increased plasma concentrations of cell-free hemoglobin and heme after transfusion of stored packed red blood cells (SRBCs) potentiate a primary injury induced by prolonged hypotension. With this proposal, we would like to extend our knowledge and explore in more detail the mechanisms by which cell-free hemoglobin and transfusion of SRBCs might aggravate VILI. Since blood transfusions, hemolysis and VILI can all be found in intensive care unit patients quite frequently, we propose that increased plasma concentrations of cell-free hemoglobin accelerate the development and increase the severity of VILI while both can be attenuated by therapy with hemoglobin and heme scavengers haptoglobin or hemopexin. Furthermore, we shall evaluate the effects of transfusion of SRBCs on the development and aggravation of VILI including protective effects of haptoglobin and hemopexin. Both, VILI and transfusion of SRBCs independently induce systemic pro-oxidant and pro-inflammatory effects. Therefore, we shall explore pulmonary and additional extra-pulmonary foci of inflammation and apoptosis in VILI with and without transfusion of SRBCs. This will help advance our understanding on the aspects of organ cross talk in ARDS. In addition, we aim to evaluate the effects of intravascular hemolysis on pulmonary capillary perfusion.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Roland Francis