Haeme oxygenase and nitric oxide synthetase blockade and brain blood flow in sheep exposed to carbon monoxide

Carbon monoxide (CO) usually does not damage the brain cortex in our in vivo model. To investigate the possible protective role of responsive and regulated changes in blood flow, 24 ewes were randomly assigned in equal numbers to sham-control, CO-control and treatment (haeme oxygenase (HO) and nitric oxide synthetase (NOS) inhibited) groups. Sheep in the second and third groups were then anaesthetised with CO for 2 h. Brain blood flow was measured using Laser Doppler and was increased in CO exposed sheep. The CO-induced anaesthesia was associated with isolated brain white matter damage. In the HO/NOS inhibited sheep, cortical EEG recovery after the anaesthesia was slower and incomplete, and cortical blood flow increased whereas white matter flow decreased. These results confirm our earlier findings that the induction of HO and NOS by CO inhalation is protective, but, suggest a relationship between tissue injury and blood flow that is perhaps partly causal.