Abstract
Hypothermia is ineffective in 45% of neonates with hypoxic-ischemic encephalopathy. Xenon has additive neuroprotective properties, but is expensive, and its application complicated. Argon gas is cheaper, easier to apply, and also has neuroprotective properties in experimental settings. The aim was to explore the safety of argon ventilation in newborn piglets.MethodsEight newborn piglets (weight 1.4–3.0 kg) were used. Heart rate, blood pressure, regional cerebral saturation, and electrocortical brain activity were measured continuously. All experiments had a 30 min. baseline period, followed by three 60 min. periods of argon ventilation alternated with 30 min argon washout periods. Two animals were ventilated with increasing concentrations of argon (1h 30%, 1 h 50%, and 1 h 80%), two were subjected to 60 min. hypoxia (FiO2 0.08) before commencing 50% argon ventilation, and two animals received hypothermia following hypoxia as well as 50% argon ventilation. Two animals served as home cage controls and were terminated immediately.ResultsArgon ventilation did not result in a significant change of heart rate (mean ± s.d. −3.5±3.6 bpm), blood pressure (−0.60±1.11 mmHg), cerebral oxygen saturation (0.3±0.9%), electrocortical brain activity (−0.4±0.7 µV), or blood gas values. Argon ventilation resulted in elevated argon concentrations compared to the home cage controls (34.5, 25.4, and 22.4 vs. 7.3 µl/ml).ConclusionVentilation with up to 80% argon during normoxia, and 50% argon after hypoxia did not affect heart rate, blood pressure, cerebral saturation and electrocortical brain activity. Clinical safety studies of argon ventilation in humans seem justified.
Highlights
Perinatal asphyxia in full term neonates is an important cause of mortality and morbidity
Brain injury following hypoxia-ischemia is partly mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor
A subgroup of animals was subjected to hypoxia and subsequent hypothermia to mimic the conditions during which argon will be used in clinical settings
Summary
Perinatal asphyxia in full term neonates is an important cause of mortality and morbidity. [3] The noble gas xenon exhibits non-competitive antagonism of this NDMA receptor and results of its use as an additive neuroprotective agent are promising. [4,5,6] Xenon is an expensive gas and requires complex closed-circuit ventilation systems. [9,10,11,12,13,14] In contrast with xenon, argon is a more abundant and cheaper noble gas. It can be obtained as a pure gas of pharmaceutical quality at low costs and does not require complex ventilator setups. The aim of the present study was to explore the safety of argon ventilation in newborn piglets
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