Early changes in cerebral metabolism after perinatal hypoxia-ischemia: a study in normothermic and hypothermic piglets

Abstract

Introduction: Hypoxic ischemic encephalopathy (HIE) after a perinatal insult is a dynamic process that evolves over time. Therapeutic hypothermia (TH) is standard treatment for severe to moderate HIE. There is a lack of evidence on the temporal change and interrelation of the underlying mechanisms that constitute HIE under normal and hypothermic conditions. We aimed to describe early changes in intracerebral metabolism after a hypoxic-ischemic insult in piglets treated with and without TH and in controls.

Methods: Three devices were installed into the left hemisphere of 24 piglets: a probe measuring intracranial pressure, a probe measuring blood flow and oxygen tension, and a microdialysis catheter measuring lactate, glucose, glycerol, and pyruvate. After a standardized hypoxic ischemic insult, the piglets were randomized to either TH or normothermia.

Results: Glycerol, a marker of cell lysis, increased immediately after the insult in both groups. There was a secondary increase in glycerol in normothermic piglets but not in piglets treated with TH. Intracerebral pressure, blood flow, oxygen tension, and extracellular lactate remained stable during the secondary increase in glycerol.

Conclusion: This exploratory study depicted the development of the pathophysiological mechanisms in the hours following a perinatal hypoxic-ischemic insult with and without TH and controls.

Keywords: animal model; cerebral metabolism changes; glycerol; hypoxic-ischemic encephalopathy; therapeutic hypothermia.

Figure 1

Vital signs at baseline, during hypoxia, and the first 24 h of observation in piglets subjected to a hypoxic-ischemic insult with or without therapeutic hypothermia and controls. Data are mean and standard deviation. #, indicates significance in HI vs. controls; $, indicates significance in HI + TH vs. control; §, indicates significance in HI vs. HI + TH.

Figure 2

Intracerebral microdialysis data for baseline and the first 24 h in piglets subjected to a hypoxic-ischemic insult with or without therapeutic hypothermia and controls. Data are mean and standard deviation. #, indicates significance in HI vs. controls; $, indicates significance in HI + TH vs. control; §, indicates significance in HI vs. HI + TH.

Figure 3

Glycerol levels during the first 24 h of observation in eight piglets subjected to a hypoxic-ischemic insult without treatment with therapeutic hypothermia. Animals who presented with seizures are marked with red.

Figure 4

Relationship between insult severity and secondary cell death. Cell death is measured as area under the curve for glycerol during the whole 24-h observation period. Insult severity measured as: (A) duration of EEG suppression, (B) end-hypoxia blood lactate, (C) end-hypoxia blood pH, and (D) end-hypoxia blood base excess. AUC, area under the curve; EEG, electroencephalography.

Figure 5

Probe and NIRS data from baseline, during the insult, and for the first 24 h in piglets subjected to a hypoxic-ischemic insult with or without therapeutic hypothermia and controls. Data are mean and standard deviation. #, indicates significance in HI vs. controls; $, indicates significance in HI + TH vs. control; §, indicates significance in HI vs. HI + TH. ICP, intracranial pressure; NIRS, near-infrared spectroscopy; BPU, blood perfusion units; rSO₂, regional cerebral oxygenation.