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 flow. Inappropriate synthesis of vasodilatory nitric oxide may be important in this respect. We investigated if nitric oxide synthesis inhibition by N(omega)-nitro-L-arginine (NLA) could restore cerebral autoregulation after severe hypoxia-ischemia (HI). HI was induced in 15 newborn lambs. Cerebral blood flow (carotid artery blood flow [ml/min]: Qcar) and mean aortic blood pressure [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 post-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 with an upper limit of regulatory ability between 75 and 90 mm Hg. At 0-30 post-HI, all groups lacked autoregulatory ability of the cerebral vascular bed and showed an aortic blood pressure-passive Q(car). At 60-120 post-HI autoregulation was restored in NLA-10 and NLA-40-treated lambs (upper limit of autoregulation was shifted to higher MABP in NLA40-treated lambs), but not in placebo-treated lambs. At 60-120 post-HI MABP was higher in both NLA-groups 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 impairment of the autoregulatory ability of the cerebral vascular bed. Even low-dose nitric oxide-synthesis inhibition started upon reperfusion restored autoregulation, suggesting a role for nitric oxide-induced vasodilation in the impairment of autoregulation of the cerebral blood flow after birth asphyxia.
Dorrepaal
C A
CA
TNO, Institute for Prevention and Health, Leiden, The Netherlands.
Steendijk
P
P
Baan
J
J
van Bel
F
F
D000818:Animals; D000831:Animals, Newborn; D001158:Arteries; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D007700:Kinetics; D009569:Nitric Oxide / Q000096:biosynthesis*; D010100:Oxygen / Q000097:blood; D012756:Sheep
D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen