Inhibition of nitric oxide synthesis following severe hypoxia-ischemia restores autoregulation of cerebral blood flow in newborn lambs

Birth asphyxia impairs the autoregulatory ability of the cerebral blood flo w. Inappropriate synthesis of vasodilatory nitric oxide may be important in this respect. We investigated if nitric oxide synthesis inhibition by N-om ega-nitro-L-arginine (NLA) could restore cerebral autoregulation after seve re hypoxia-ischemia (HI). HI was induced in 15 newborn lambs. Cerebral bloo d flow (carotid artery blood flow [ml/min]: Q(car)) and mean aortic blood p ressure [mmHg]: MABP) were measured over a 30 min period before HI (pre-HI) , 0-30 min after completion of HI (0-30 post-HI) and from 60 to 120 min pos t-HI (60-120 post-HI). Immediately after completion of HI, 5 lambs received a placebo (PLAC), 5 low dose NLA (10 mg/kg/iv: NLA-10) and 5 high dose NLA (40 mg/kg/iv: NLA-40). Pre-HI, all groups showed cerebral autoregulation w ith an upper limit of regulatory ability between 75 and 90 mm Hg. At 0-30 p ost-HI, all groups lacked autoregulatory ability of the cerebral vascular b ed and showed an aortic blood pressure-passive Q(car). At 60-120 post-HI au toregulation was restored in NLA-10 and NLA-40-treated lambs (upper limit o f autoregulation was shifted to higher MABP in NLA40-treated lambs), but no t in placebo-treated lambs. At 60-120 post-HI MABP was higher in both NLA-g roups than in PLAC group (83+/-15 [NLA-10] and 78+/-14 [NLA-40] vs. 65+/-9 mmHg [PLAC], P<0.05). We conclude that severe HI in newborn lambs induces i mpairment of the autoregulatory ability of the cerebral vascular bed. Even low-dose nitric oxide-synthesis inhibition started upon reperfusion restore d autoregulation, suggesting a role for nitric oxide-induced vasodilation i n the impairment of autoregulation of the cerebral blood flow after birth a sphyxia. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.