EFFECT OF POST-HYPOXIC-ISCHEMIC INHIBITION OF NITRIC-OXIDE SYNTHESIS ON CEREBRAL BLOOD-FLOW, METABOLISM AND ELECTROCORTICAL BRAIN ACTIVITY IN NEWBORN LAMBS

Since an excessive production of nitric oxide upon reperfusion/reoxyge nation may play an important role in post-hypoxic-ischemic (HI) brain injury, we investigated whether immediate post-HI blockade of nitric o xide synthesis by N-omega-nitro-L-arginine (NLA) may reduce this injur y. In 18 newborn lambs, subjected to severe HI, changes from pre-HI va lues were measured for carotid blood flow (Qcar [ml/min]) as a measure of changes in brain blood flow, (relative) cerebral metabolic rate of oxygen (CMRO2), and electrocortical brain activity (ECBA) at 15, 60, 120 and 180 min after HI. Upon completion of HI, at the onset of reper fusion and reoxygenation, 6 lambs received a placebo (control group), 6 low-dose NLA (10 mg/kg i.v., NLA-10 group), and 6 high-dose NLA (40 mg/kg i.v., NLA-40 group). Histological damage to cerebellar Purkinje cells was assessed after termination of the experiment. Only the contr ol group showed a distinct initial post-HI cerebral hyperperfusion. Fr om 60 min after HI onward Qcar was decreased to about 75% of pre-HI Qc ar in all 3 groups, although none of these changes in Qcar reached sta tistical significance. Despite the decreased Qcar in all 3 groups, onl y the control group showed a significantly decreased CMRO2. ECBA and i ts bandwidth decreased in all groups, but only recovered in the NLA-10 group 180 min after HI. The brain to body mass ratio (%) and percenta ge necrotic Purkinje cells were, respectively: 15.3 +/- 0.8 and 56 +/- 10(control group); 12.5 +/- 1.2 and 36 +/- 9 (NLA-10 group), and 11.3 +/- 1.0 (p < 0.05 vs. the control group) and 35 +/- 14 (NLA-40 group) . Since post-HI reperfusion injury of the brain has been characterized by a decreased CMRO2 and electrical brain activity, we conclude that preservation of CMRO2 in both NLA groups, but a recovery of ECBA and i ts bandwidth only in the NLA-10 group, suggests that NLA, and especial ly low-dose NLA, may reduce post-HI brain injury.