Rapid Oxygen Titration Following Cardiopulmonary Resuscitation Mitigates Cerebral Overperfusion and Striatal Mitochondrial Dysfunction in Asphyxiated Newborn Lambs

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2024 Nov 22

PMID 39576879

Authors

Shiraz Badurdeen

Robert Galinsky

Calum T Roberts

Kelly J Crossley

Valerie A Zahra

Alison Thiel

Yen Pham

Peter G Davis

Stuart B Hooper

Graeme R Polglase

Emily J Camm

Affiliations

Soon will be listed here.

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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