AUTHOR=Linardi Daniele , Mani Romel , Murari Angela , Dolci Sissi , Mannino Loris , Decimo Ilaria , Tessari Maddalena , Martinazzi Sara , Gottin Leonardo , Luciani Giovanni B. , Faggian Giuseppe , Rungatscher Alessio TITLE=Nitric Oxide in Selective Cerebral Perfusion Could Enhance Neuroprotection During Aortic Arch Surgery JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=8 YEAR=2022 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.772065 DOI=10.3389/fcvm.2021.772065 ISSN=2297-055X ABSTRACT=Background

Hypothermic circulatory arrest (HCA) in aortic arch surgery has a significant risk of neurological injury despite the newest protective techniques and strategies. Nitric oxide (NO) could exert a protective role, reduce infarct area and increase cerebral perfusion. This study aims to investigate the possible neuroprotective effects of NO administered in the oxygenator of selective antegrade cerebral perfusion (SCP) during HCA.

Methods

Thirty male SD adult rats (450–550 g) underwent cardiopulmonary bypass (CPB), cooling to 22°C body core temperature followed by 30 min of HCA. Rats were randomized to receive SCP or SCP added with NO (20 ppm) administered through the oxygenator (SCP-NO). All animals underwent CPB-assisted rewarming to a target temperature of 35°C in 60 min. At the end of the experiment, rats were sacrificed, and brain collected. Immunofluorescence analysis was performed in blind conditions.

Results

Neuroinflammation assessed by allograft inflammatory factor 1 or ionized calcium-binding adapter molecule 1 expression, a microglia activation marker was lower in SCP-NO compared to SCP (4.11 ± 0.59 vs. 6.02 ± 0.18%; p < 0.05). Oxidative stress measured by 8oxodG, was reduced in SCP-NO (0.37 ± 0.01 vs. 1.03 ± 0.16%; p < 0.05). Brain hypoxic area extent, analyzed by thiols oxidation was attenuated in SCP-NO (1.85 ± 0.10 vs. 2.74 ± 0.19%; p < 0.05). Furthermore, the apoptotic marker caspases 3 was significantly reduced in SCP-NO (10.64 ± 0.37 vs. 12.61 ± 0.88%; p < 0.05).

Conclusions

Nitric oxide administration in the oxygenator during SCP and HCA improves neuroprotection by decreasing neuroinflammation, optimizing oxygen delivery by reducing oxidative stress and hypoxic areas, finally decreasing apoptosis.