Differential metabolomic signatures in plasma and urine under mild and moderate hypothermia during cardiopulmonary bypass

While the organ-protective effects of hypothermia during cardiopulmonary bypass (CPB) are well known, the metabolomic impacts of different hypothermia levels remain unclear. This study aimed to evaluate the effects of mild (32-35 °C, n = 15) and moderate (26-31 °C, n = 14) hypothermia on plasma and urinary metabolomic profiles in adults undergoing CPB. Untargeted metabolomic analysis was conducted using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF-MS), which identified 137 plasma and 101 urinary metabolites. Statistical and multivariate analyses revealed significant differences in metabolic profiles between the two groups. In plasma, reduced levels of citric acid, proline, and inosine were observed in the mild hypothermia group, whereas myristic acid and glyceraldehyde levels were lower in the moderate group. In urine, the mild hypothermia group showed increased levels of creatinine and 5,6-dihydroxyeicosatrienoic acid (5,6-DHET), along with decreased levels of 2-hydroxybutyric acid, N-acetylserine, and oxaloacetic acid, indicating reduced renal stress. Conversely, elevated levels of C17-sphinganine and ceramides in the moderate group suggested altered lipid metabolism and greater cellular stress. Moderate hypothermia was associated with higher metabolic stress, whereas mild hypothermia was associated with relative metabolic stability. These findings present candidate biomarkers for optimizing hypothermia strategies during CPB.