[abstract] EFFECTS OF PHOSPHODIESTERASE-5 INHIBITORS ON CEREBRAL BLOOD FLOW AND SEIZURES IN RATS EXPOSED TO HBO2.

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[abstract] EFFECTS OF PHOSPHODIESTERASE-5 INHIBITORS ON CEREBRAL BLOOD FLOW AND SEIZURES IN RATS EXPOSED TO HBO2.

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Title: [abstract] EFFECTS OF PHOSPHODIESTERASE-5 INHIBITORS ON CEREBRAL BLOOD FLOW AND SEIZURES IN RATS EXPOSED TO HBO2.
Author: Demchenko, IT; Ruehle, A; Allen, BW; Vann, RD; Piantadosi, CA
Abstract: INTRODUCTION: HBO2 is a potent cerebral vasoconstrictor, but prolonged exposure stimulates brain nitric oxide (NO) production, reversing vasoconstriction and increasing cerebral blood flow (CBF)—a trigger for O2 convulsions. Cerebral vasoconstriction may be mitigated by phosphodiesterase-5 (PDE5) inhibitors, such as sildenafil (Viagra) or tadalafil (Cialis), which inhibit cyclic guanosine monophosphate (cGMP) degradation, enhancing and prolonging the NO vasodilator effect. Therefore, we tested the hypothesis that administering PDE5 inhibitors before HBO2 opposes hyperoxic vasoconstriction and accelerates oxygen seizure development. METHODS: First, total and regional (striatal) CBF (tCBF, rCBF) were measured by hydrogen clearance in anesthetized rats breathing air before and after the administration of sildenafil (1.4 mg/kg), tadalafil (0.3 mg/kg), L-NAME (30 mg/kg) or the NO donor SNAP (0.1 mg/kg). Second, tCBF and rCBF were measured in anesthetized rats pretreated with sildenafil, tadalafil, L-NAME, or sildenafil and L-NAME combined, then exposed to 6 ATA O2. Third, convulsion latency was determined in conscious rats pretreated with sildenafil and exposed to 4 ATA O2. In anesthetized rats, arterial BP, EEG, blood gases and body temperature were monitored and controlled; EEG spikes were used as markers of CNS oxygen toxicity. RESULTS: In anesthetized rats breathing air, sildenafil and tadalafil had statistically insignificant effects on basal CBF, unless cGMP production was stimulated with an NO donor. Anesthetized rats treated with sildenafil or tadalafil and exposed to 6 ATA O2 showed significantly greater increases in CBF and shorter seizure latencies than untreated controls. PDE5 inhibitors did not increase CBF in rats pretreated with L-NAME before exposure to 6 ATA O2. Conscious rats pretreated with sildenafil before HBO2 were more susceptible to CNS O2 toxicity, indicated by a 27% shorter convulsive latency than controls. CONCLUSIONS: PDE5 inhibitors (sildenafil and tadalafil) oppose hyperoxic vasoconstriction and decrease HBO2 safety by hastening the onset of CNS O2 toxicity. Sponsored by DAN and ONR
Description: Abstract of the Undersea & Hyperbaric Medical Society 2008 Annual Scientific Meeting June 26-28, 2008 Salt Lake City Marriott Downtown, Salt Lake City, Utah.
URI: http://archive.rubicon-foundation.org/7893
Date: 2008

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  • UHMS Meeting Abstracts
    This is a collection of the published abstracts from the Undersea and Hyperbaric Medical Society (UHMS) annual meetings.

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