Rapid oxygen titration following cardiopulmonary resuscitation mitigates cerebral overperfusion and striatal mitochondrial dysfunction in asphyxiated newborn lambs

Badurdeen, S.; Galinsky, R.; Roberts, C.; Crossley, K. J.; Zahra, V.; Thiel, A.; Pham, Y.; Davis, P.; Hooper, S. B.; Polglase, G.; Camm, E.

doi:10.1101/2024.07.27.603805

bioRxiv · 10.1101/2024.07.27.603805

Rapid oxygen titration following cardiopulmonary resuscitation mitigates cerebral overperfusion and striatal mitochondrial dysfunction in asphyxiated newborn lambs

Badurdeen, S.·Galinsky, R.·Roberts, C.·Crossley, K. J.·Zahra, V.·Thiel, A.·Pham, Y.·Davis, P.·Hooper, S. B.·Polglase, G.·Camm, E.

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Abstract

Asphyxiated neonates must have oxygenation rapidly restored to limit ongoing hypoxic-ischemic injury. However, the effects of transient hyperoxia after return of spontaneous circulation (ROSC) are poorly understood. We randomly allocated acutely asphyxiated, near-term lambs to cardiopulmonary resuscitation in 100% oxygen ("standard oxygen", n=8) or air (n=7) until 5 minutes after ROSC, or to resuscitation in 100% oxygen immediately weaned to air upon ROSC ("rapid-wean", n=7). From 5 minutes post-ROSC, oxygen was titrated to target preductal oxygen saturation between 90-95%. Cerebral tissue oxygenation was transiently but markedly elevated following ROSC in the standard oxygen group compared to the air and rapid-wean groups. The air group had a delayed rise in cerebral tissue oxygenation from 5 minutes after ROSC coincident with up-titration of oxygen. These alterations in oxygen kinetics corresponded with similar overshoots in cerebral perfusion (pressure and flow), indicating a physiological mechanism. Transient cerebral tissue hyperoxia in the standard oxygen and air groups resulted in significant alterations in mitochondrial respiration and dynamics, relative to the rapid-wean group. Overall, rapid-wean of oxygen following ROSC preserved striatal mitochondrial respiratory function and reduced the expression of genes involved in free radical generation and apoptosis, suggesting a potential therapeutic strategy to limit cerebral reperfusion injury.

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Badurdeen, S., Galinsky, R., Roberts, C., Crossley, K. J., Zahra, V., Thiel, A., Pham, Y., Davis, P., Hooper, S. B., Polglase, G., Camm, E.. 2024-07-29. Rapid oxygen titration following cardiopulmonary resuscitation mitigates cerebral overperfusion and striatal mitochondrial dysfunction in asphyxiated newborn lambs. https://doi.org/10.1101/2024.07.27.603805

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