The Effects of Anaesthesia on Cell Death in a Porcine Model of Neonatal Hypoxic-ischaemic Brain Injury

Overview

Journal BJA Open

Specialty Anesthesiology

Date 2024 May 14

PMID 38741692

Authors

Julia K Gundersen

Ela Chakkarapani

David A Menassa

Lars Walloe

Marianne Thoresen

Affiliations

Soon will be listed here.

Abstract

Background: Hypothermia is neuroprotective after neonatal hypoxic-ischaemic brain injury. However, systemic cooling to hypothermic temperatures is a stressor and may reduce neuroprotection in awake pigs. We compared two experiments of global hypoxic-ischaemic injury in newborn pigs, in which one group received propofol-remifentanil and the other remained awake during post-insult hypothermia treatment.

Methods: In both studies, newborn pigs were anaesthetised using halothane during a 45-min global hypoxic-ischaemic insult induced by reducing io and graded hypotension until a low-voltage <7 μV electroencephalogram was achieved. On reoxygenation, the pigs were randomly allocated to receive 24 h of normothermia or hypothermia. In the first study (=18) anaesthesia was discontinued and the pigs' tracheas were extubated. In the second study (=14) anaesthesia was continued using propofol and remifentanil. Brain injury was assessed after 72 h by classical global histopathology, Purkinje cell count, and apoptotic cell counts in the hippocampus and cerebellum.

Results: Global injury was nearly 10-fold greater in the awake group compared with the anaesthetised group (=0.021). Hypothermia was neuroprotective in the anaesthetised pigs but not the awake pigs. In the hippocampus, the density of cleaved caspase-3-positive cells was increased in awake compared with anaesthetised pigs in normothermia. In the cerebellum, Purkinje cell density was reduced in the awake pigs irrespective of treatment, and the number of cleaved caspase-3-positive Purkinje cells was greatly increased in hypothermic awake pigs. We detected no difference in cleaved caspase-3 in the granular cell layer or microglial reactivity across the groups.

Conclusions: Our study provides novel insights into the significance of anaesthesia/sedation during hypothermia for achieving optimal neuroprotection.

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