title: Nitric oxide synthesis inhibition during cerebral hypoxemia and reoxygenation with 100% oxygen in newborn pigs.
abstract: The objective of our study was to evaluate the effects of N(sigma)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the nitric oxide (NO) pathway, on cerebral microcirculation during hypoxemia and reoxygenation with 100% oxygen in newborn pigs. Twenty-two pigs were randomized to hypoxemia [inspired fraction of oxygen (FIO(2)) 0.08; 20 min] and reoxygenation (FIO(2) 1.0; 60 min) or normoxia. The hypoxemic animals were further randomized to receive either an intravenous bolus injection of 5 mg/kg L-NAME (n = 8) or a corresponding volume of isotonic saline (n = 8) 30 min before the onset of hypoxemia. The normoxemic group (n = 6) received the same pretreatment with L-NAME. Cerebral hemodynamics were assessed by laser Doppler flowmetry and intracranial pressure monitoring. The cerebral NO concentration was continuously measured using an electrochemical sensor. Pretreatment with L-NAME resulted in a more severe systemic hypotension and reduced cerebral microcirculation during the period of hypoxemia compared with the saline/hypoxemia group. NO synthesis inhibition during reoxygenation with 100% oxygen, however, blunted the increase in NO concentration (p < 0.05) without reduction of cerebral blood flow and cerebral perfusion pressure. In conclusion, in this newborn pig model, pretreatment with a bolus infusion of L-NAME induced severe hypotension and reduced cerebral microcirculation during hypoxemia. However, it appears to have no significant adverse effect on cerebral hemodynamics during the period of reoxygenation with 100% oxygen. This deleterious effect during hypoxemia limits the use of L-NAME as a preventive drug but suggests beneficial effects during reoxygenation with 100% oxygen.
authors.affiliation: Department of Pediatric Research, National Hospital, Ulleval University Hospital, Oslo, Norway. stefan.kutzsche@klinmed.uio.no
authors.forename: Stefan
authors.initials: S
authors.lastname: Kutzsche
authors.forename: Anne-Beate
authors.initials: AB
authors.lastname: Solas
authors.forename: Torstein
authors.initials: T
authors.lastname: Lyberg
authors.forename: Ola D
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced; D002534:Hypoxia, Brain / Q000503:physiopathology*; D007427:Intracranial Pressure; D017078:Laser-Doppler Flowmetry; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000008:administration & dosage*; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester