A PIGLET SURVIVAL MODEL OF POSTHYPOXIC ENCEPHALOPATHY

The aim of this study was to produce a neonatal piglet mode which, avo iding vessel ligation, exposed the whole animal to hypoxia and produce d dose-dependent clin encephalopathy and neuropathologic damage simila r to that seen after birth asphyxia. Twenty-three piglets were halotha ne-anesthezied. Hypoxia was induced in 19 piglets by reducing the frac tional concentration of inspired oxygen (Fio(2)) to the maximum concen tration at which the EEG amplitude was below 7 mu V (low amplitude) fo r 17-55 min. There were transient increases in Fio(2) to correct brady cardia or hypotension. Posthypoxia, the piglets were extubated when br eathing was stable. Four were sham-treated controls. We aimed at 72-h survival; seven died prematurely due to posthypoxic complications. EEG and a videotaped itemized neurologic assessment were recorded We foun d that 95% of the animals showed neuropathologic damage. The duration of low amplitude EEG during the insult and the arterial pH at the end of the insult correlated with cortical/white matter damage; r = 0.75 a nd 0.81, respectively. Early postinsult EEG background amplitude (r = 0.86 at 3 h) and neurologic score (r = 0.79 at 8 h) correlated with ne uropathology. Epileptic seizures in seven animals were always associat ed with severe neuropathologic damage. We conclude that EEG-controlled hypoxia and subsequent intensive care enabled the animals to survive with an encephalopathy which correlated with the cerebral hypoxic insu lt. The encephalopathy was clinically, electrophysiologically, and neu ropathologically similar to that in the asphyxiated term infant. This model is suitable for examining mechanisms of damage and evaluation of potential protective therapies after birth asphyxia.