Future work

There is little doubt that more work needs to be conducted to draw any firm conclusions on the immunomodulatory potential of lung ventilation during surgery with CPB. Although our model was unique and had strength in that it enabled the patient to serve as their own control, it was a challenging experimental model to undertake which is an important consideration for any future work. The reasons for this include the difficultly of ensuring that all five blood samples were obtained (including the sample form the left pulmonary vein which was often challenging to obtain for anatomical reasons), as well as undertaking the complex surgical and ventilatory protocols. A suggested model to consider in any future work would involve a control cohort design where one cohort of patients undergoing on-pump CABG surgery received bilateral ventilation during CPB while a control group received no ventilation during CPB. In each group, blood entering the lung via the central venous blood could then be sampled following CPB which would represent blood entering the lungs. This could then be compared with blood from the radial arterial line (which is routinely inserted), to represent blood exiting the lungs. This would allow a transpulmonary assessment of blood constituents in both the ventilated and unventilated cohorts to assess the impact of ventilation during CPB without the requirement to obtain direct pulmonary vein samples.

It is noteworthy that previous research has demonstrated higher levels of anti-inflammatory cytokine concentrations in bronchoalveolar lavage (BAL) fluid in a group of patients ventilated during CPB compared to a control cohort receiving no ventilation during CPB.(60) This raises the question as to whether assessment of BAL fluid cytokine concentrations would be beneficial in assessing the direct effects of lung ventilation during CPB. Due to the technical complexities of our study we were unable to facilitate an assessment of the impact of ventilation during CPB on BAL cytokine concentrations. However, this is an interesting area for future research as high levels of inflammatory cytokines within BAL fluid following surgery with CPB may be responsible for the pooling of neutrophils in the alveolar space thus predisposing to pulmonary dysfunction and ARDS. A one-lung ventilation model with subsequent BAL of the ventilated and unventilated lung would serve as a model to investigate this further. In addition, there has been recent interest in future lung protection therapies such as inhaled hydrogen sulphide which has been shown in an animal model to protect against ventilator-associated lung injury.(118) Our novel one-lung ventilation model during CPB would provide a potential clinical platform to test this further by facilitating application

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of hydrogen sulphide to one lung during CPB with subsequent assessment of BAL fluid cytokine concentrations while the unventilated lung serves as the patient’s own control.

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PUBLICATIONS ARISING FROM THIS WORK

Funston, W., Ruchaud-Sparagano, M.H., Scott, J., O’Leary, D., Dark, J.H., Simpson, A.J. The immunological impact of lung ventilation during cardiopulmonary bypass. American Journal of Respiratory and Critical Care Medicine 2018;197: A2989

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