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Objective To characterize the institutional oxygen management practices during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery, including any potential changes during an 8-year study period. Design A retrospective cohort study. Setting A tertiary care cardiac surgical program. Participants Patients who underwent cardiac surgery involving CPB, with or without hypothermic circulatory arrest (HCA), between January 1, 2010, and December 31, 2017. Measurements and Main Results In addition to baseline patient characteristics, the authors recorded the partial pressures of arterial oxygen (Pa o 2), fraction of inspired oxygen, and mixed venous oxygen saturation during CPB of 696 randomly selected patients during an 8-year study period. The overall mean Pa o 2 was 255 ± 48 mmHg, without any significant change during the 8-year study period (p = 0.30). The mean Pa o 2 of HCA patients was significantly higher than in patients without HCA (327 ± 93 mmHg v 252 ± 45 mmHg, respectively; p Conclusions The current approach to oxygen management during CPB at the authors’ institution is within the range of hyperoxemic levels, and these practices have not changed over time. The impact of these practices on patients’ outcomes is not fully understood, and additional studies are needed to establish firm evidence to guide optimal oxygen management practice during CPB.

HMG-CoA reductase, the proximal rate-limiting enzyme in the mevalonate pathway, is inhibited by statins. Beyond their cholesterol lowering impact, statins have pleiotropic effects and their use is linked to improved lung health. We have shown that mevalonate cascade inhibition induces apoptosis and autophagy in cultured human airway mesenchymal cells. Here, we show that simvastatin also induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in these cells. We tested whether coordination of ER stress, autophagy and apoptosis determines survival or demise of human lung mesenchymal cells exposed to statin. We observed that simvastatin exposure activates UPR (activated transcription factor 4, activated transcription factor 6 and IRE1α) and caspase-4 in primary human airway fibroblasts and smooth muscle cells. Exogenous mevalonate inhibited apoptosis, autophagy and UPR, but exogenous cholesterol was without impact, indicating that sterol intermediates are involved with mechanisms mediating statin effects. Caspase-4 inhibition decreased simvastatin-induced apoptosis, whereas inhibition of autophagy by ATG7 or ATG3 knockdown significantly increased cell death. In BAX-/-/BAK-/- murine embryonic fibroblasts, simvastatin-triggered apoptotic and UPR events were abrogated, but autophagy flux was increased leading to cell death via necrosis. Our data indicate that mevalonate cascade inhibition, likely associated with depletion of sterol intermediates, can lead to cell death via coordinated apoptosis, autophagy, and ER stress. The interplay between these pathways appears to be principally regulated by autophagy and Bcl-2-family pro-apoptotic proteins. These findings uncover multiple mechanisms of action of statins that could contribute to refining the use of such agent in treatment of lung disease. © 2014 Elsevier B.V.