Lack of melatonin secretion induced by moderate hypothermia during aortic-arch surgery, possible implications in neurological outcomes.

Preclinical data from the peculiar animal model of "synthetic torpor" (ST), a reversible hypothermic condition resembling natural torpor but pharmacologically induced in rats (a non-hibernating mammal), suggest that in hypothermic conditions the neuroprotective effects of melatonin are strongly enhanced. As a protection technique, during aortic-arch surgery patients are induced a hypothermia similar to ST. Since in ST systemic melatonin was found particularly high, our aim was to assay serum melatonin in patients (N=8) undergoing aortic surgery, either during hypothermia and in the following four recovery days. Serum markers of blood-brain barrier (BBB) integrity (the astrocytic protein S100B) and neuronal damage (neuronal-specific enolase, NSE) were also measured. Results show that, in contrast to what observed in ST, in hypothermic patients melatonin was dramatically reduced in respect to the pre-anesthesia level, slowly recovering during the post-surgery period. Also, S100B and NSE raised during surgery, indicating highly leaking BBB and some ongoing neuronal damage, though both markers returned closer to pre-anesthesia levels within recovery period. Together, present results show that, in aortic-arch surgery, hypothermic patients totally lack the systemic melatonin peak that was observed in ST, the BBB was temporarily compromised and some acute neuronal damage occurred. A main implication of this work is that, exploiting the low BBB efficiency that makes easier to reach brain parenchyma, by administering melatonin during the hypothermic stage of the surgery the observed gap could be filled, possibly triggering the neuroprotective mechanism seen in preclinical observations and leading to better neurological outcomes for this surgical procedure. HighlightsO_LIDuring hypothermia induced in aortic-surgery systemic melatonin was low C_LIO_LISerum biomarkers enlighten transient blood-brain barrier and neuronal sufferings C_LIO_LIGiving melatonin during aortic-surgery hypothermia may improve neurological outcome C_LI