title: Effects of hyperosmolar mannitol on regional oxygen supply and consumption in the newborn pig.
abstract: Previous work indicated that opening the blood-brain barrier with hyperosmotic mannitol decreased local venous O2 saturation and increased cerebral O2 consumption. This study was performed to assess the vascular effect of hypertonic mannitol on oxygen supply/consumption balance in the newborn pig and to determine the role of nitric oxide in mediating the effects of mannitol. Animals were anesthetized with alpha-chloralose and mechanically ventilated to maintain their blood gases within normal range. Retrograde catheterization of the right carotid artery was performed to inject 12 ml to 25% mannitol over a 30 sec interval. In one group of animals (n = 5), the blood-brain barrier transfer coefficient (Ki) to 14C-alpha aminoisobutyric acid or 14C-urea (n = 4) was measured 12 min after mannitol. In another group of animals (n = 9), regional cerebral blood flow and small vein O2 saturation was measured using 14C-iodoantripyrine and microspectrophotometry. Similar measurements were made in other groups of animals (n = 9) after pretreatment with 10 mg kg-1 i.v. of N-omega-nitro-L-arginine methyl ester (L-NAME), 20 min before mannitol injection. The mannitol injection did not increase Ki or local cerebral O2 consumption. It resulted in a decreased small vein O2 saturation in the ipsilateral cortex (46 +/- 3%) in comparison to the contralateral cortex (55 +/- 2%). The O2 supply/consumption ratio decreased in the ipsilateral cortex in the mannitol injected animals (2.14 +/- 0.23) in comparison to the contralateral cortex (2.76 +/- 0.28). Pretreatment with L-NAME abolished this effect of mannitol (small vein O2 saturation 59 +/- 2% in ipsilateral cortex and 58 +/- 2% in the contralateral cortex; O2 supply/consumption 2.68 +/- 0.17 in the ipsilateral cortex and 2.65 +/- 0.16 in the contralateral cortex). We conclude that hypertonic mannitol adversely affects O2 supply/consumption balance, without increasing blood-brain barrier transport, and this effect is blocked by L-NAME, a nitric oxide synthase antagonist.
authors.affiliation: Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
authors.forename: M
authors.initials: M
authors.lastname: Anwar
authors.forename: J A
authors.initials: JA
authors.lastname: Williams
authors.forename: H R
authors.initials: HR
authors.lastname: Weiss
mesh_terms: D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006982:Hypertonic Solutions / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects*; D013053:Spectrophotometry; D013552:Swine; D014018:Tissue Distribution; D014508:Urea / Q000493:pharmacokinetics
chemical_list: D000621:Aminoisobutyric Acids; D004791:Enzyme Inhibitors; D006982:Hypertonic Solutions; D008353:Mannitol; D014508:Urea; D019001:Nitric Oxide Synthase; D010100:Oxygen; D000983:Antipyrine; C008135:iodoantipyrine; D019331:NG-Nitroarginine Methyl Ester