Blockade of haem oxygenase and nitric oxide synthetase causes cortical dysfunction in sheep exposed to carbon...

Twenty adult ewes underwent common surgery and following recovery were exposed to 1% carbon monoxide (CO) for 2 h. Ten of these sheep were randomly selected for treatment with haem oxygenase (HO) and nitric oxide synthetase (NOS) blockers. All sheep were killed 5 days later. The CO exposure was narcotic and EEG frequency was suppressed. The EEG recovery was rapid in the control sheep and both slow and incomplete in the treated sheep. This difference was statistically significant (P<0.05). For the first time in our CO studies in sheep, one showed multiple cortical infarcts. This sheep was blocked for HO and NOS function. No significant differences were seen in peri-ventricular white matter infarction distribution and frequency. We have previously shown brain protection against CO- and inert diluent-hypoxemia by way of an increase in brain blood flow (BBF) that maintains adequate brain O2 uptake, and by an increase in circulating red blood cells. From this study, we propose that the induction of neuronal and glial HO and NOS in sheep exposed to CO is protective, especially for the cortex. We intend to study this further by both selective and collective enzyme blockade and by measuring regional BBF changes.