Effects of hyperosmolar mannitol on regional oxygen supply and consumption in the newborn pig

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.